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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 -
European Heart Journal. Case Reports Jun 2024Previous literature suggests that patients with transthyretin amyloidosis (ATTR) experience a high burden of ventricular arrhythmias. Despite this evidence, optimal...
BACKGROUND
Previous literature suggests that patients with transthyretin amyloidosis (ATTR) experience a high burden of ventricular arrhythmias. Despite this evidence, optimal strategies for arrhythmia prevention and treatment remain subject to debate.
CASE SUMMARY
We report the case of a patient with hereditary ATTR cardiomyopathy who developed recurrent ventricular tachycardia prior to a decline in his left ventricular ejection fraction (LVEF). Although he ultimately received an intracardiac device (ICD) for secondary prevention of ventricular tachycardia, his clinical course begets the question of whether more aggressive arrhythmia prevention upfront could have prevented his global functional decline.
DISCUSSION
Given the advent of new disease-modifying therapies for ATTR, it is imperative to reconsider antiarrhythmic strategies in these patients. New decision tools are needed to decide what additional parameters (beyond LVEF ≤ 35%) may warrant ICD placement for primary prevention of ventricular arrhythmias in these patients.
PubMed: 38912115
DOI: 10.1093/ehjcr/ytae273 -
Journal of the American Heart... Jun 2024Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective...
BACKGROUND
Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the prevalence and prognostic impact of AS among patients with CA.
METHODS AND RESULTS
We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light-chain (AL) CA. CA patients' echocardiograms were re-analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population-based controls, all types of CA had higher age- and sex-standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) [1.09-3.64]; ATTRv: SRR, 3.41; 95%CI [1.64-4.60]; ATTRwt: SRR, 10.8; 95%CI [5.25-14.53]). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI [0.56-1.14]; ATTRv: SRR, 1.27; 95%CI [0.85-1.44]; ATTRwt: SRR, 4.01; 95%CI [2.71-4.54]). Among patients with ATTRwt, moderate or greater AS was not associated with increased all-cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI [0.42-1.19]; =0.19).
CONCLUSIONS
Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.
PubMed: 38904242
DOI: 10.1161/JAHA.124.034723 -
Respirology Case Reports Jun 2024Amyloidosis is a pathological deposition disease that causes a spectrum of organ dysfunction. Pulmonary involvement is generally associated with immunoglobulin light...
Amyloidosis is a pathological deposition disease that causes a spectrum of organ dysfunction. Pulmonary involvement is generally associated with immunoglobulin light chain type (AL) amyloid. Transthyretin (ATTR) amyloid build up in the lung is thought to be a senile disease observed usually as a finding at autopsy. We describe a case of pulmonary ATTR amyloidosis with concurrent mycobacterial tuberculosis infection.
PubMed: 38903946
DOI: 10.1002/rcr2.1418 -
World Journal of Clinical Cases Jun 2024Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice, with amyloidosis and fibrillary glomerulonephritis being the two most...
BACKGROUND
Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice, with amyloidosis and fibrillary glomerulonephritis being the two most frequently encountered entities. Renal amyloid heavy and light chain (AHL) is relatively uncommon and its biopsy diagnosis is usually limited to cases that show strong equivalent staining for a single immunoglobulin (Ig) heavy chain and a single light chain, further supported by mass spectrometry (MS) and serum studies for monoclonal protein. But polyclonal light chain staining can pose a challenge.
CASE SUMMARY
Herein we present a challenging case of renal AHL with polyclonal and polytypic Ig gamma (IgG) staining pattern by immunofluorescence. The patient is a 62-year-old Caucasian male who presented to an outside institution with a serum creatinine of up to 8.1 mg/dL and nephrotic range proteinuria. Despite the finding of a polyclonal and polytypic staining pattern on immunofluorescence, ultrastructural study of the renal biopsy demonstrated the presence of fibrils with a mean diameter of 10 nm. Congo red was positive while DNAJB9 was negative. MS suggested a diagnosis of amyloid AHL type with IgG and lambda, but kappa light chains were also present supporting the immunofluorescence staining results. Serum immunofixation studies demonstrated IgG lambda monoclonal spike. The patient was started on chemotherapy. The chronic renal injury however was quite advanced and he ended up needing dialysis shortly after.
CONCLUSION
Tissue diagnosis of AHL amyloid can be tricky. Thorough confirmation using other available diagnostic techniques is recommended in such cases.
PubMed: 38898862
DOI: 10.12998/wjcc.v12.i17.3200 -
Current Oncology Reports Jun 2024This review aims to assess the therapeutic strategies available for relapsed/refractory patients with immunoglobulin light chain (AL) amyloidosis who received upfront... (Review)
Review
PURPOSE OF REVIEW
This review aims to assess the therapeutic strategies available for relapsed/refractory patients with immunoglobulin light chain (AL) amyloidosis who received upfront daratumumab-based regimens.
RECENT FINDINGS
The treatment landscape of AL amyloidosis has changed radically thanks to the introduction in the upfront setting of daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone (DaraCyBorD) which improved patients' outcomes increasing the rate of hematologic and organ responses. However, many patients eventually relapse or are refractory to daratumumab and the best salvage therapy is not well defined yet. In this contest, we reviewed the available therapeutic options after daratumumab failure, and we look towards the current advances in Bcl-2 inhibitors, novel immunotherapeutic agents as chimeric antigen receptor (CAR-T) therapy and bispecific antibodies (bsAbs). Relapsed/refractory AL amyloidosis represent an unmet clinical need and novel targeted drugs require urgent prospective assessment.
PubMed: 38896184
DOI: 10.1007/s11912-024-01561-2 -
Journal of Clinical Medicine May 2024Cardiac amyloidosis, a condition characterized by abnormal protein deposition in the heart, leads to restrictive cardiomyopathy and is notably associated with an... (Review)
Review
Cardiac amyloidosis, a condition characterized by abnormal protein deposition in the heart, leads to restrictive cardiomyopathy and is notably associated with an increased risk of arrhythmias and conduction disorders. This article reviews the current understanding and management strategies for these cardiac complications, with a focus on recent advancements and clinical challenges. The prevalence and impact of atrial arrhythmias, particularly atrial fibrillation, are examined, along with considerations for stroke risk and anticoagulation therapy. The article also addresses the complexities of managing rate and rhythm control, outlining the utility and limitations of pharmacological agents and interventions such as catheter ablation. Furthermore, it reviews the challenges in the treatment of ventricular arrhythmias, including the contentious use of implantable cardioverter-defibrillators for primary and secondary prevention. Individualized approaches, considering the unique characteristics of cardiac amyloidosis, are paramount. Continuous research and clinical exploration are essential to refine treatment strategies and improve outcomes in this challenging patient population.
PubMed: 38892799
DOI: 10.3390/jcm13113088 -
European Journal of Heart Failure Jun 2024The 2021 European Society of Cardiology (ESC) screening recommendations for individuals carrying a pathogenic transthyretin amyloidosis variant (ATTRv) are based on...
AIMS
The 2021 European Society of Cardiology (ESC) screening recommendations for individuals carrying a pathogenic transthyretin amyloidosis variant (ATTRv) are based on expert opinion. We aimed to (i) determine the penetrance of ATTRv cardiomyopathy (ATTRv-CM) at baseline; (ii) examine the value of serial evaluation; and (iii) establish the yield of first-line diagnostic tests (i.e. electrocardiogram, echocardiogram, and laboratory tests) as per 2021 ESC position statement.
METHODS AND RESULTS
We included 159 relatives (median age 55.6 [43.2-65.9] years, 52% male) at risk for ATTRv-CM from 10 centres. The primary endpoint, ATTRv-CM diagnosis, was defined as the presence of (i) cardiac tracer uptake in bone scintigraphy; or (ii) transthyretin-positive cardiac biopsy. The secondary endpoint was a composite of heart failure (New York Heart Association class ≥II) and pacemaker-requiring conduction disorders. At baseline, 40/159 (25%) relatives were diagnosed with ATTRv-CM. Of those, 20 (50%) met the secondary endpoint. Indication to screen (≤10 years prior to predicted disease onset and absence of extracardiac amyloidosis) had an excellent negative predictive value (97%). Other pre-screening predictors for ATTRv-CM were infrequently identified variants and male sex. Importantly, 13% of relatives with ATTRv-CM did not show any signs of cardiac involvement on first-line diagnostic tests. The yield of serial evaluation (n = 41 relatives; follow-up 3.1 [2.2-5.2] years) at 3-year interval was 9.4%.
CONCLUSIONS
Screening according to the 2021 ESC position statement performs well in daily clinical practice. Clinicians should adhere to repeating bone scintigraphy after 3 years, as progressing to ATTRv-CM without signs of ATTRv-CM on first-line diagnostic tests or symptoms is common.
PubMed: 38887861
DOI: 10.1002/ejhf.3339 -
JAAD Case Reports Jul 2024
PubMed: 38883180
DOI: 10.1016/j.jdcr.2024.04.033 -
Nature Communications Jun 2024Systemic AL amyloidosis is one of the most frequently diagnosed forms of systemic amyloidosis. It arises from mutational changes in immunoglobulin light chains. To...
Systemic AL amyloidosis is one of the most frequently diagnosed forms of systemic amyloidosis. It arises from mutational changes in immunoglobulin light chains. To explore whether these mutations may affect the structure of the formed fibrils, we determine and compare the fibril structures from several patients with cardiac AL amyloidosis. All patients are affected by light chains that contain an IGLV3-19 gene segment, and the deposited fibrils differ by the mutations within this common germ line background. Using cryo-electron microscopy, we here find different fibril structures in each patient. These data establish that the mutations of amyloidogenic light chains contribute to defining the fibril architecture and hence the structure of the pathogenic agent.
Topics: Humans; Cryoelectron Microscopy; Immunoglobulin Light-chain Amyloidosis; Immunoglobulin Light Chains; Mutation; Amyloid; Male; Female; Middle Aged
PubMed: 38879609
DOI: 10.1038/s41467-024-49520-6