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Giornale Italiano Di Cardiologia (2006) Jul 2024Aortic valve stenosis and cardiac amyloidosis, particularly transthyretin-related, often coexist and share a common clinical and demographic profile. Several... (Review)
Review
Aortic valve stenosis and cardiac amyloidosis, particularly transthyretin-related, often coexist and share a common clinical and demographic profile. Several pathophysiological hypotheses have been proposed regarding the causes of this association, neither of which fully substantiated in practice. The key to detect the coexistence of cardiac amyloidosis and aortic valve stenosis lies in clinical suspicion. It is possible to hypothesize concurrent cardiac amyloidosis in patients with aortic valve stenosis with the aid of clinical, electrocardiographic, echocardiographic, and extracardiac "red flags". Subsequent non-invasive diagnostic steps are often sufficient to establish a definitive diagnosis. The early diagnosis of this condition is pivotal since the presence of dual pathology worsens patient's prognosis, especially without intervention. Available data on treatment show a better outcome in terms of survival and cardiovascular events in patients undergoing percutaneous correction of valvular heart disease rather than medical therapy alone, regardless of the presence of cardiac amyloidosis. Furthermore, it seems that cardiac amyloidosis does not impact survival after transcatheter aortic valve replacement, even if higher rates of rehospitalizations have been described. Indeed, percutaneous treatment of valvular heart disease is currently considered the primary therapeutic option. Subsequently a disease-modifying treatment for transthyretin amyloidosis may be considered in order to delay disease progression and improve outcomes, even if specific data are still lacking.
Topics: Humans; Aortic Valve Stenosis; Prognosis; Amyloidosis; Cardiomyopathies; Amyloid Neuropathies, Familial; Echocardiography
PubMed: 38916463
DOI: 10.1714/4282.42635 -
Pathological evaluation of the pathogenesis of diabetes mellitus and diabetic peripheral neuropathy.Pathology International Jun 2024Currently, there are more than 10 million patients with diabetes mellitus in Japan. Therefore, the need to explore the pathogenesis of diabetes and the complications... (Review)
Review
Currently, there are more than 10 million patients with diabetes mellitus in Japan. Therefore, the need to explore the pathogenesis of diabetes and the complications leading to its cure is becoming increasingly urgent. Pathological examination of pancreatic tissues from patients with type 2 diabetes reveals a decrease in the volume of beta cells because of a combination of various stresses. In human type 2 diabetes, islet amyloid deposition is a unique pathological change characterized by proinflammatory macrophage (M1) infiltration into the islets. The pathological changes in the pancreas with islet amyloid were different according to clinical factors, which suggests that type 2 diabetes can be further subclassified based on islet pathology. On the other hand, diabetic peripheral neuropathy is the most frequent diabetic complication. In early diabetic peripheral neuropathy, M1 infiltration in the sciatic nerve evokes oxidative stress or attenuates retrograde axonal transport, as clearly demonstrated by in vitro live imaging. Furthermore, islet parasympathetic nerve density and beta cell volume were inversely correlated in type 2 diabetic Goto-Kakizaki rats, suggesting that diabetic peripheral neuropathy itself may contribute to the decrease in beta cell volume. These findings suggest that the pathogenesis of diabetes mellitus and diabetic peripheral neuropathy may be interrelated.
PubMed: 38888200
DOI: 10.1111/pin.13458 -
Predictors of developing renal dysfunction following diagnosis of transthyretin cardiac amyloidosis.Clinical Cardiology Jun 2024In patients with transthyretin cardiac amyloidosis (ATTR-CA), renal dysfunction is a poor prognostic indicator. Limited data are available on variables that portend...
BACKGROUND
In patients with transthyretin cardiac amyloidosis (ATTR-CA), renal dysfunction is a poor prognostic indicator. Limited data are available on variables that portend worsening renal function (wRF) among ATTR-CA patients.
OBJECTIVES
This study assesses which characteristics place patients at higher risk for the development of wRF (defined as a drop of ≥10% in glomerular filtration rate [GFR]) within the first year following diagnosis of ATTR-CA.
METHODS
We included patients with ATTR-CA (n = 134) evaluated between 2/2016 and 12/2022 and followed for up to 1 year at our amyloid clinic. Patients were stratified into two groups: a group with maintained renal function (mRF) and a group with wRF and compared using appropriate testing. Significant variables in the univariate analysis were included in the multivariable logistic regression model to determine characteristics associated with wRF.
RESULTS
Within a follow-up period of 326 ± 118 days, the median GFR% change measured -6% [-18%, +8]. About 41.8% (n = 56) had wRF, while the remainder had mRF. In addition, in patients with no prior history of chronic kidney disease (CKD), 25.5% developed de novo CKD. On multivariable logistic regression, only New York Heart Association (NYHA) class ≥III (odds ratio [OR]: 3.9, 95% confidence interval [CI]: [1.6-9.3]), history of ischemic heart disease (IHD) (OR: 0.3, 95% CI: [0.1-0.7]), and not receiving SGLT-2i (OR: 0.1, 95% CI: [0.02-0.5]) were significant predictors of wRF.
CONCLUSION
Our study demonstrated that the development of de novo renal dysfunction or wRF is common following the diagnosis of ATTR-CA. Additionally, we identified worse NYHA class and no prior history of IHD as significant predictors associated with developing wRF, while receiving SGLT-2i therapy appeared to be protective in this population.
Topics: Humans; Male; Female; Glomerular Filtration Rate; Amyloid Neuropathies, Familial; Aged; Cardiomyopathies; Prognosis; Retrospective Studies; Risk Factors; Middle Aged; Follow-Up Studies; Renal Insufficiency, Chronic; Disease Progression; Kidney; Time Factors; Incidence; Risk Assessment
PubMed: 38873847
DOI: 10.1002/clc.24298 -
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 the American College of... Jun 2024Transthyretin cardiomyopathy (ATTR-CM) was an exclusion criterion in randomized clinical trials of sodium-glucose cotransporter 2 inhibitors (SGLT2i).
BACKGROUND
Transthyretin cardiomyopathy (ATTR-CM) was an exclusion criterion in randomized clinical trials of sodium-glucose cotransporter 2 inhibitors (SGLT2i).
OBJECTIVES
This study sought to assess the effectiveness and tolerability of SGLT2i in patients with ATTR-CM.
METHODS
Data of 2,356 consecutive ATTR-CM patients (2014-2022) were analyzed: 260 (11%) received SGLT2i. After comparing the groups according to the treatment, 14 variables were significantly different-age and N-terminal pro-B-type natriuretic peptide were included in the model. A propensity score reflecting the likelihood of being treated with SGLT2i for each patient was determined using 16 variables.
RESULTS
The study comprised 220 patients treated with SGLT2i (age 77 ± 2 years; 82.3% wild-type ATTR-CM; left ventricular ejection fraction 45.8% ± 11%) and 220 propensity-matched control individuals. Adequacy of matching was verified (standardized differences: <0.10 between groups). Discontinuation rate for SGLT2i was 4.5%; at 12 months, SGLT2i treatment was associated with less worsening of NYHA functional class, N-terminal pro-B-type natriuretic peptide, estimated glomerular filtration rate, and fewer new initiations of loop diuretic agent therapy. Over 28 months (Q1-Q3: 18-45 months), SGLT2i therapy was associated with lower all-cause mortality (HR: 0.57; 95% CI: 0.37-0.89; P = 0.010), cardiovascular mortality (HR: 0.41; 95% CI: 0.24-0.71; P < 0.001), heart failure (HF) hospitalization (HR: 0.57; 95% CI: 0.36-0.91; P = 0.014), and the composite outcome of cardiovascular mortality and HF hospitalization (HR: 0.57; 95% CI: 0.38-0.84; P = 0.003).
CONCLUSIONS
SGLT2i treatment in ATTR-CM patients was well tolerated and associated with favorable effects on HF symptoms, renal function, and diuretic agent requirement over time. SGLT2i treatment was associated with reduced risk of HF hospitalization and cardiovascular and all-cause mortality, regardless of the ejection fraction, despite the effect size being likely overestimated. In the absence of randomized trials, these data may inform clinicians regarding the use of SGLT2i in patients with ATTR-CM.
Topics: Humans; Male; Female; Aged; Sodium-Glucose Transporter 2 Inhibitors; Amyloid Neuropathies, Familial; Cardiomyopathies; Retrospective Studies; Treatment Outcome
PubMed: 38866445
DOI: 10.1016/j.jacc.2024.03.429 -
Current Opinion in Neurology Jun 2024The association between clonal haematological disorders and peripheral nerve disease is recognized. Paraproteinaemic phenomena are the most common mechanism, but direct...
PURPOSE OF REVIEW
The association between clonal haematological disorders and peripheral nerve disease is recognized. Paraproteinaemic phenomena are the most common mechanism, but direct neural lymphomatous infiltration is seen and can be challenging to diagnose. Traditional and novel anticancer therapies have neuropathic side effects.
RECENT FINDINGS
Novel studies using sensitive techniques are refining the incidence of peripheral neuropathy in patients with a monoclonal gammopathy, and the pathogenesis of IgM Peripheral neuropathy (PN) and POEMS syndrome. Recent series give insight into the characteristics and diagnostic challenges of patients with neurolymphomatosis and amyloid light chain amyloidosis. There is an increasing repertoire of effective anticancer drugs in haematological oncology, but chemotherapy-related neuropathy remains a common side effect.
SUMMARY
This review of the current literature focuses on recent updates and developments for the paraproteinaemic neuropathies, and the evaluation, diagnosis and treatment of peripheral nerve disease due to high-grade and low-grade lymphomas and lymphoproliferative disorders.
PubMed: 38861221
DOI: 10.1097/WCO.0000000000001291 -
Heart Failure Clinics Jul 2024Transthyretin amyloid cardiomyopathy (ATTR-CM) is a relatively prevalent cause of morbidity and mortality. Over the recent years, development of disease-modifying... (Review)
Review
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a relatively prevalent cause of morbidity and mortality. Over the recent years, development of disease-modifying treatments has enabled stabilization of the circulating transthyretin tetramer and suppression of its hepatic production, resulting in a remarkable improvement in survival of patients with ATTR-CM. Second-generation drugs for silencing are currently under investigation in randomized clinical trials. In vivo gene editing of transthyretin has been achieving unanticipated suppression of hepatic production in ATTR-CM. Trials of antibodies inducing the active removal of transthyretin amyloid deposits in the heart are ongoing, and evidence has gathered for exceptional spontaneous regression of ATTR-CM.
Topics: Humans; Amyloid Neuropathies, Familial; Cardiomyopathies; Benzoxazoles; Prealbumin
PubMed: 38844305
DOI: 10.1016/j.hfc.2024.03.005 -
Heart Failure Clinics Jul 2024Transthyretin amyloid cardiomyopathy (ATTR-CM) is caused by the myocardial extracellular deposition of amyloid fibrils formed from the dissociation of TTR tetramer into... (Review)
Review
Transthyretin amyloid cardiomyopathy (ATTR-CM) is caused by the myocardial extracellular deposition of amyloid fibrils formed from the dissociation of TTR tetramer into monomers. The rate-limiting step in TTR amyloidogenesis is the dissociation of the TTR tetramer into monomers: Tafamidis is an effective TTR-stabilizer in its native homotetrameric structure. Tafamidis is a safe and effective drug in reducing symptoms, hospitalization and mortality in accurately selected patients affected by hereditary and wild-type transthyretin amyloid cardiomyopathy.
Topics: Humans; Benzoxazoles; Amyloid Neuropathies, Familial; Cardiomyopathies; Prealbumin
PubMed: 38844304
DOI: 10.1016/j.hfc.2024.03.007 -
Heart Failure Clinics Jul 2024Hereditary transthyretin-related amyloidosis (hATTR) is the most common form of familial amyloidosis. It is an autosomal dominant disease caused by a pathogenic variant... (Review)
Review
Hereditary transthyretin-related amyloidosis (hATTR) is the most common form of familial amyloidosis. It is an autosomal dominant disease caused by a pathogenic variant in the TTR gene. More than 140 TTR gene variants have been associated with hATTR, with the Val30Met variant representing the most common worldwide. The clinical phenotype varies according to the gene variant and includes predominantly cardiac, predominantly neurologic, and mixed phenotypes. The present review aims to describe the genotype-phenotype correlations in hATTR. Understanding these correlations is crucial to facilitate the early identification of the disease, predict adverse outcomes, and guide management with approved disease-modifying therapies.
Topics: Humans; Amyloid Neuropathies, Familial; Prealbumin; Phenotype; Mutation; Genetic Association Studies; Genotype
PubMed: 38844302
DOI: 10.1016/j.hfc.2024.03.006 -
Heart Failure Clinics Jul 2024Cardiac amyloidosis (CA) is caused by the myocardial deposition of misfolded proteins, either amyloid transthyretin (ATTR) or immunoglobulin light chains (AL). The... (Review)
Review
Cardiac amyloidosis (CA) is caused by the myocardial deposition of misfolded proteins, either amyloid transthyretin (ATTR) or immunoglobulin light chains (AL). The paradigm of this condition has transformed, since CA is increasingly recognized as a relatively prevalent cause of heart failure. Cardiac scintigraphy with bone tracers is the unique noninvasive technique able to confirm CA without performing tissue biopsy or advanced imaging tests. A moderate-to-intense myocardial uptake (Perugini grade ≥2) associated with the absence of a monoclonal component is greater than 99% specific for ATTR-CA, while AL-CA confirmation requires tissue biopsy.
Topics: Humans; Cardiomyopathies; Amyloidosis; Radiopharmaceuticals; Radionuclide Imaging; Bone and Bones; Myocardium; Amyloid Neuropathies, Familial; Heart Failure; Prealbumin
PubMed: 38844301
DOI: 10.1016/j.hfc.2024.03.003