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Current Treatment Options in... Dec 2023Sudden cardiac arrest is associated with high morbidity and mortality. Despite having a disproportionate burden of sudden cardiac death (SCD), rates of primary and...
PURPOSE OF REVIEW
Sudden cardiac arrest is associated with high morbidity and mortality. Despite having a disproportionate burden of sudden cardiac death (SCD), rates of primary and secondary prevention of SCD with implantable cardioverter-defibrillator (ICD) therapy are lower among eligible racially minoritized patients. This review highlights the racial and ethnic disparities in ICD utilization, associated barriers to ICD care, and proposed interventions to improve equitable ICD uptake.
RECENT FINDINGS
Racially minoritized populations are disproportionately eligible for ICD therapy but are less likely to see cardiac specialists, be counseled on ICD therapy, and ultimately undergo ICD implantation, fueling disparate outcomes. Racial disparities in ICD utilization are multifactorial, with contributions at the patient, provider, health system, and structural/societal level.
SUMMARY
Racial and ethnic disparities have been demonstrated in preventing SCD with ICD use. Proposed strategies to mitigate these disparities must prioritize care delivery and access to care for racially minoritized patients, increase the diversification of clinical and implementation trial participants and the healthcare workforce, and center reparative justice frameworks to rectify a long history of racial injustice.
PubMed: 38873495
DOI: 10.1007/s11936-023-01025-z -
Frontiers in Cardiovascular Medicine 2024Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly...
BACKGROUND
Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly understood.
PURPOSE
This study aims to analyze the effects of extracellular volume (ECV) expansion, a surrogate marker of amyloid burden on myocardial blood flow (MBF), myocardial work efficiency (MWE), and left ventricular (LV) systolic dysfunction in AL amyloidosis.
METHODS
Subjects with biopsy-proven AL amyloidosis were prospectively enrolled (April 2016-June 2021; Clinicaltrials.gov ID NCT02641145) and underwent cardiac magnetic resonance imaging (MRI) to quantify rest MBF by perfusion imaging, LV ejection fraction (LVEF) by cine MRI, and ECV by pre- and post-contrast T1 mapping. The MWE was estimated as external cardiac work from the stroke volume and mean arterial pressure normalized to the LV myocardial mass.
RESULTS
Rest MBF in 92 subjects (62 ± 8 years, 52 men) with AL amyloidosis averaged 0.87 ± 0.21 ml/min/g and correlated with MWE ( = 0.42; < 0.001). Rest MBF was similarly low in subjects with sustained hematologic remission after successful AL amyloidosis therapy ( = 21), as in those with recently diagnosed AL amyloidosis. Both MBF and MWE decreased by ECV tertile ( < 0.01 for linear trends). The association of ECV with MWE comprised a direct effect (84% of the total effect; < 0.001) on MWE from adverse interstitial remodeling assessed by ECV and an indirect effect (16% of the total effect; < 0.001) mediated by MBF. There was a significant base-to-apex gradient of rest MBF in subjects with higher amyloid burden.
CONCLUSIONS
In AL amyloidosis, both MBF and MWE decrease as cardiac amyloid burden and ECV expansion increase. Both structural and vascular changes from ECV expansion and myocardial amyloid burden appear to contribute to lower MWE.
PubMed: 38873265
DOI: 10.3389/fcvm.2024.1371810 -
Coexistence of variant-type transthyretin and immunoglobulin light-chain amyloidosis: a case report.European Heart Journal. Case Reports Jun 2024Determining the type of amyloid deposits is clinically important for choosing the specific therapies for cardiac amyloidosis.
BACKGROUND
Determining the type of amyloid deposits is clinically important for choosing the specific therapies for cardiac amyloidosis.
CASE SUMMARY
A 78-year-old woman who had been experiencing fluid retention and dyspnoea on exertion for 6 months was referred to our hospital for the management of heart failure with left ventricular hypertrophy. Since Tc-hydroxymethylene diphosphonate scintigraphy showed mild cardiac uptake and significant elevation of serum free lambda chain (with a difference of 263 mg/L in free light chain), we suspected immunoglobulin light-chain amyloidosis (AL), and endomyocardial biopsy was performed. The deposit site within the myocardial tissue exhibited positive for Congo red staining and transthyretin immunostaining, however negative or non-specific for light-chain immunostaining including lambda and kappa staining. Genetic testing confirmed a mutation in V122I, variant-type transthyretin amyloidosis (ATTRv). Despite the administration of patisiran, her condition exhibited progressive deterioration. Additionally, she displayed macroglossia, an atypical manifestation in ATTRv amyloidosis. Further biopsies from tongue and abdominal wall fat culminated in a final diagnosis: the coexistence of ATTRv and AL (of the lambda type). Although treatment with melphalan and dexamethasone was started, she passed away 24 months after the initial visit. When the endomyocardial biopsy specimen underwent mass spectrometry as a analysis, both ATTR and AL amyloid were significantly detected.
DISCUSSION
Coexistence of ATTRv and AL within cardiac amyloidosis is extremely uncommon. In situations where incongruities arise between the amyloid type determined via immunohistochemistry findings and the amyloid type assumed based on other clinical findings, mass spectrometry should be considered.
PubMed: 38872953
DOI: 10.1093/ehjcr/ytae264 -
Case Reports in Gastroenterology 2024AL amyloidosis can involve the gastrointestinal (GI) tract in a sporadic manner, affecting certain anatomical areas while sparing others.
INTRODUCTION
AL amyloidosis can involve the gastrointestinal (GI) tract in a sporadic manner, affecting certain anatomical areas while sparing others.
CASE PRESENTATION
Our patient with AL amyloidosis and confirmed colonic involvement was found to have new odynophagia, GI bleeding, and imaging findings that might suggest AL amyloidosis. However, negative pathology results from esophageal biopsies suggested the patient's new ulcerations were more likely a side effect of her autologous stem cell transplant (SCT) and chemotherapy meant to target amyloidosis, as opposed to an effect of amyloid infiltration itself.
CONCLUSION
GI involvement of amyloidosis requires a high degree of clinical suspicion and should be considered in patients with systemic diseases affecting the kidney, heart, and GI tract; however, when satisfactory biopsies obtained from endoscopy results are negative, other causes should be considered.
PubMed: 38872730
DOI: 10.1159/000538947 -
Scientific Reports Jun 2024Tafamidis is the world's first and only oral drug approved to treat the rare disease transthyretin amyloid cardiomyopathy (ATTR-CM). Medicines are known to have...
Tafamidis is the world's first and only oral drug approved to treat the rare disease transthyretin amyloid cardiomyopathy (ATTR-CM). Medicines are known to have different adverse reactions during the course of treatment. However, the current limited clinical studies did not identify significant adverse drug reactions to tafamidis. Tafamidis has been on the market for 5 years now, a large number of adverse drug event (ADE) reports with tafamidis as the primary suspected drug have been reported in the United Food and Drug Administration's adverse event reporting system (FAERS). We retrieved 8170 adverse event reports in FAERS with tafamidis as the first suspected drug, and mined these reports for positive signals to perform risk warnings for potentially possible adverse events with tafamidis. We found that a large number of adverse events associated with the primary disease were reported due to insufficient awareness of ATTR among the reporters, leading to a large number of positive signals reported in the cardiac disorders system. We also found that tafamidis has the potential to cause an adverse event risks of ear and labyrinth disorders system and urinary tract infection bacterial, which deserve continued clinical attention.
Topics: United States; Humans; United States Food and Drug Administration; Adverse Drug Reaction Reporting Systems; Benzoxazoles; Amyloid Neuropathies, Familial; Drug-Related Side Effects and Adverse Reactions; Product Surveillance, Postmarketing; Male
PubMed: 38871835
DOI: 10.1038/s41598-024-64697-y -
Journal of Comparative Effectiveness... Jun 2024The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy... (Review)
Review
The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy (CM) trials, including transthyretin-mediated amyloidosis with CM (ATTR-CM), are often limited to hospitalization and mortality. To investigate the relationship between the 6MWT and hospitalization or mortality in CM, including ATTR-CM. A PRISMA-guided systematic literature review was conducted using search terms for CM, 6MWT, hospitalization and mortality. Forty-one studies were identified that reported 6MWT data and hospitalization or mortality data for patients with CM. The data suggest that a greater 6MWT distance is associated with a reduced risk of hospitalization or mortality in CM. The 6MWT is an accepted alternative end point in CM trials, including ATTR-CM.
PubMed: 38869839
DOI: 10.57264/cer-2023-0158 -
Journal of Investigative Medicine : the... Jun 2024Cardiac amyloidosis (CA) is an infiltrative restrictive cardiomyopathy caused by the deposition of amyloid fibrils in the myocardium. It manifests in two primary... (Review)
Review
Cardiac amyloidosis (CA) is an infiltrative restrictive cardiomyopathy caused by the deposition of amyloid fibrils in the myocardium. It manifests in two primary subtypes: transthyretin cardiac amyloidosis (ATTR) and immunoglobulin light chain cardiac amyloidosis (AL). ATTR is further classified into wild-type (wtATTR) and hereditary (hATTR) based on transthyretin gene mutation. Advances in diagnostics and therapeutics have transformed CA from a rare and untreatable condition to a more prevalent and manageable disease. Non-invasive diagnostic tools such as electrocardiography, echocardiography, and cardiac magnetic resonance can raise suspicion for CA; bone scintigraphy can non-invasively confirm ATTR, while AL necessitates histological confirmation. The severity of ATTR and AL can be assessed through serum biomarker-based staging. Treatment approaches differ, ranging from silencing or stabilizing transthyretin and degrading amyloid fibrils in ATTR to employing anti-plasma cell therapies and autologous stem cell transplantation in AL.
PubMed: 38869161
DOI: 10.1177/10815589241261279 -
American Journal of Nephrology Jun 2024Amyloidosis includes a diverse group of rare diseases characterized by the misfolding of native or mutant proteins, leading to extracellular accumulation in various... (Review)
Review
BACKGROUND
Amyloidosis includes a diverse group of rare diseases characterized by the misfolding of native or mutant proteins, leading to extracellular accumulation in various organs. While 42 proteins have been identified to date, their distribution differs between systemic and localized forms.
SUMMARY
Mass spectrometry analysis of tissue samples in the US show immunoglobulin light chain (AL) amyloidosis as the most prevalent systemic type, followed by transthyretin (ATTR). Heart and kidney involvement are common. Although there are 14 recognized types of kidney-related amyloidosis, clinicopathologic studies in the US have identified 11 types, with AL amyloidosis being the most prevalent cause of kidney involvement.
PubMed: 38865984
DOI: 10.1159/000539596 -
Clinical Rheumatology Jun 2024Extrahepatic manifestations in patients with primary biliary cholangitis (PBC) are frequently observed recently. We aimed in this study to explore the...
BACKGROUND
Extrahepatic manifestations in patients with primary biliary cholangitis (PBC) are frequently observed recently. We aimed in this study to explore the clinicopathological characteristics and prognosis of glomerulonephritis in patients with PBC.
METHODS
Consecutive PBC patients admitted to Peking Union Medical College Hospital from January 2002 to May 2019 were retrospectively enrolled. PBC patients with other autoimmune diseases which may have nephritis were excluded. Structured interview, systemic rheumatologic examination, and laboratory tests were conducted for each patient. Literature about patients with PBC and glomerulonephritis was reviewed and summarized.
RESULTS
Among the 330 PBC patients enrolled, glomerulonephritis were identified in 10 patients (3.0%). Eight (80.0%) were females and 2 (20.0%) were males. The mean age was 58.4 ± 9.5 years old. Membranous nephropathy (MN) was revealed in 4 patients, IgA nephropathy (IgA N) in 2 patients, minimal change disease (MCD) in 2 patients, mesangial proliferative glomerulonephritis in 1 patient, and renal amyloidosis in 1 patient. Compared to the literature reviewed, 10 cases of MN, 1 case of MCD, 1 case of IgA N, and 1 case of acute poststreptococcal glomerulonephritis (APSGN) were observed.
CONCLUSIONS
Glomerulonephritis may not be a well-recognized feature of PBC and is not a rare complication and deserved to be routinely screened in clinical practice. As MN is the most common form of glomerulonephritis in PBC patients and PBC can be asymptomatic at an early stage, patients presented with MN should be screened for PBC, so to avoid cirrhosis. Key Points • Patients with primary biliary cholangitis (PBC) can be complicated with glomerulonephritis, and membranous nephropathy (MN) is the most common form.
PubMed: 38865027
DOI: 10.1007/s10067-024-06994-5 -
ChemMedChem Jun 2024Proteinopathies or amyloidoses are a group of life-threatening disorders that result from misfolding of proteins and aggregation into toxic insoluble amyloid aggregates....
Proteinopathies or amyloidoses are a group of life-threatening disorders that result from misfolding of proteins and aggregation into toxic insoluble amyloid aggregates. Amyloid aggregates have low clearance from the body due to the insoluble nature, leading to their deposition in various organs and consequent organ dysfunction. While amyloid deposition in the central nervous system leads to neurodegenerative diseases that mostly cause dementia and difficulty in movement, several other organs, including heart, liver and kidney are also affected by systemic amyloidoses. Regardless of the site of amyloid deposition, misfolding and structural alteration of the precursor proteins play the central role in amyloid formation. Kinetic stabilizers are an emerging class of drugs, which act like pharmacological chaperones to stabilize the native state structure of amyloidogenic proteins and to increase the activation energy barrier that is required for adopting a misfolded structure or conformation, ultimately leading to the inhibition of protein aggregation. In this review, we discuss the kinetic stabilizers that stabilize the native quaternary structure of transthyretin, immunoglobulin light chain and superoxide dismutase 1 that cause transthyretin amyloidoses, light chain amyloidosis and familial amyotrophic lateral sclerosis, respectively.
PubMed: 38863235
DOI: 10.1002/cmdc.202400244