Recent insights have led to the development of novel pharmacotherapies with the potential to significantly impact each disease Natural history and outcome in systemic AA amyloidosis. So amjloidose, a scale designed to classify the severity of this disease has not yet been validated. The median survival time and the 3-year death-free rate after diagnosis in all-cause and cardiac deaths were Amyloidosis; Computed tomography; Lungs; Pulmonary calcifications. Newer therapies for amyloid cardiomyopathy.
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In other countries, demographics differ. Clues to the diagnosis include ventricular "hypertrophy" seen on echocardiography with inappropriately low electrical voltages on electrocardiogram ECG see below. B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide are typically elevated in cardiac amyloidosis, and troponin assays are often chronically positive at low levels 0.
Transthyretin ATTR Amyloidosis Transthyretin prealbumin is an abundant protein produced by the liver and functions as a transporter of thyroxine and retinol. It normally circulates predominantly as a homotetramer, with a small amount of transthyretin circulating in monomeric form. The monomeric form of transthyretin is prone to misfold and gradually deposit as amyloid deposits.
In the case of wild-type ATTR, the transthyretin protein is the normal nonmutated protein, and over a period of decades gradually deposits as amyloid deposits. Although small amounts of deposits can occur in the soft tissue causing carpal tunnel syndrome and vasculature, the primary pathologic deposits occur in the heart.
Patients with mutant ATTR were born with a pathologic mutation in the transthyretin gene, leading to accelerated amyloid deposition. In the United States, by far the most commonly encountered mutation is the VI mutation; it is present in Diagnosis Definitive diagnosis of amyloidosis requires biopsy.
The abdominal fat pad is sometimes chosen as a site due to the ease and low morbidity of the procedure. However, this site suffers from relatively poor sensitivity; even in positive cases, there are frequently inadequate amyloid deposits to definitively subtype the disease ATTR, AL, etc. As such, the general practice at Stanford Amyloid Center is to biopsy the clinically involved organ i. Subtyping can be performed by immunofluorescence or sent to a referral laboratory for mass spectrometry.
If there is any doubt about the diagnosis based on immunofluorescence staining, mass spectrometry should be performed. Figure 1 Endomyocardial biopsy hematoxylin and eosin stain revealing the classic pale-pink appearance of amyloid deposits surrounding each cardiomyocyte source: Stanford Amyloid Center.
Adjunctive laboratory tests for AL amyloidosis include assaying for other organ dysfunction e. Free light-chain assays can be helpful in both evaluating the likelihood of the diagnosis prior to biopsy e. In ATTR amyloidosis, it is important to offer genetic testing for the transthyretin gene.
The presence of a pathologic mutation can affect clinical trial options, predict sites of organ involvement, and have relevance for family members. In either form of cardiac amyloidosis, the dominant imaging finding is the appearance of cardiac "hypertrophy. Cardiac amyloidosis causes abnormal patterns of late gadolinium enhancement on cardiac magnetic resonance CMR in both global transmural and subendocardial distribution. The role of repeated assessments of late gadolinium enhancement or spin-lattice relaxation times on CMR or of strain assessments utilizing echocardiography is unclear.
For AL amyloidosis, it is unclear that such monitoring meaningfully adds to disease response assessments utilizing changes in serum free light chains and cardiac biomarkers. Prognosis Prognosis in amyloidosis is dependent primarily on the degree of cardiac involvement and, in AL amyloidosis, on circulating light-chain levels.
Because chemotherapy options have greatly expanded in recent years, prognosis for AL amyloidosis has markedly improved as well, with the life expectancy of most patients, including many of those with significant cardiac involvement, measured in years rather than months.
Various staging systems have been proposed for AL amyloidosis, with the majority focusing primarily on the degree of cardiac involvement. A widely utilized staging system published in relied solely on two cardiac biomarkers: troponin T or I and N-terminal pro-B-type natriuretic peptide. The staging system successfully produced distinct survival curves, though overall survival remained dismal in all 3 arms, with median survival of A revised staging system was published by the same group in , adding the absolute difference in free light chains as a third variable, thus separating patients into 4 stages.
With ongoing improvements in chemotherapy since the study period of even this second manuscript, it is likely that survival has continued to substantially improve. Treatment Treatment of AL amyloidosis follows two parallel paths: treating the consequences of the organ dysfunction while concomitantly attempting to slow progression of the disease by killing the clonal plasma cells and hence reducing the circulating pathologic light chains with chemotherapy.
Neurohormonal antagonists typically used in HF are often poorly tolerated and counterproductive. In particular, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers often lead to hypotension due to autonomic dysfunction and the presence of a small left ventricular cavity with an inability to augment stroke volume in response to vasodilation , and beta-blockers often exacerbate bradyarrhythmias.
Digoxin binds to amyloid fibrils, leading to the potential of digoxin toxicity even with normal circulating levels, and should generally be avoided. Pacemakers are frequently needed due to a high prevalence of conduction disease particularly in ATTR amyloidosis. Ventricular arrhythmias and sudden cardiac death are common as well. In ATTR amyloidosis, it is important to rule out significant neurologic involvement for patients with familial forms.
In all cases, we would recommend that transplantation only be performed in centers that are experienced with transplanting patients with amyloidosis. Over the last decade, chemotherapy options for AL amyloidosis have markedly improved, such that most patients can achieve large reductions in and sometimes complete normalization of their circulating pathologic light chains. Chemotherapy typically involves the combination of multiple classes of antineoplastics, including alkylators e.
An alternative strategy involves auto-stem-cell transplant utilizing high-dose chemotherapy with an alkylating agent. Although auto-stem-cell transplant can be an effective method of lowering light chains and is used by many centers, the only randomized trial comparing it to standard chemotherapy found auto-stem-cell transplant to have inferior outcomes. Because ATTR amyloidosis is not a malignant process, chemotherapy has no role. These include the following: Diflunisal.
This nonsteroidal anti-inflammatory drug that is approved for arthritis pain stabilizes the tetrameric form of transthyretin. A randomized trial demonstrated slowing of disease progression among patients with polyneuropathy due to mutant ATTR amyloidosis. This agent is approved in some parts of the world Europe and Japan for mutant ATTR amyloidosis causing polyneuropathy, but it is not approved in the United States.
Two agents that work via small-interfering RNA or RNA interference decreasing production of transthyretin by the liver are in Phase 3 trials for ATTR amyloidosis, including both polyneuropathy and cardiomyopathy forms.
Diagnostic clues include unexplained ventricular hypertrophy with inappropriately low ECG voltages and unexplained HF occurring with characteristic dysfunction of other organs. Definitive diagnosis requires biopsy and is crucial for definitively subtyping the amyloid deposits e.
For AL amyloidosis, treatment should begin promptly with chemotherapy our preferred option or auto-stem-cell transplant. For ATTR amyloidosis, patients should be referred for evaluation for enrollment in one of the ongoing clinical trials. For select patients, ICD implantation or cardiac transplantation should be considered. Because the disease typically requires multi-specialty expertise, we recommend referral to a high-volume amyloid center for consultation whenever possible.
The amyloidogenic VI transthyretin variant in elderly black Americans. N Engl J Med ; Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis. Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation ; Noncontrast T1 mapping for the diagnosis of cardiac amyloidosis. Causes and consequences of longitudinal LV dysfunction assessed by 2D strain echocardiography in cardiac amyloidosis. Falk RH. Pondering the prognosis and pathology of cardiac amyloidosis: answers breed questions.
Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol ; Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. Implantable cardioverter-defibrillator placement in patients with cardiac amyloidosis. Heart Rhythm ; Outcomes after heart transplantation for amyloid cardiomyopathy in the modern era.
Am J Transplant ; Changing outcomes after heart transplantation in patients with amyloid cardiomyopathy. J Heart Lung Transplant ; Heart transplantation and cardiac amyloidosis: approach to screening and novel management strategies. Autologous stem cell transplant after heart transplant for light chain AI amyloid cardiomyopathy.
High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA ; Accessed December 22, National Institutes of Health website.
Como tratar o paciente com amiloidose cardíaca?
In other countries, demographics differ. Clues to the diagnosis include ventricular "hypertrophy" seen on echocardiography with inappropriately low electrical voltages on electrocardiogram ECG see below. B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide are typically elevated in cardiac amyloidosis, and troponin assays are often chronically positive at low levels 0. Transthyretin ATTR Amyloidosis Transthyretin prealbumin is an abundant protein produced by the liver and functions as a transporter of thyroxine and retinol. It normally circulates predominantly as a homotetramer, with a small amount of transthyretin circulating in monomeric form. The monomeric form of transthyretin is prone to misfold and gradually deposit as amyloid deposits. In the case of wild-type ATTR, the transthyretin protein is the normal nonmutated protein, and over a period of decades gradually deposits as amyloid deposits.
Tipo de Amiloidoses
Yozshulrajas Myocardial uptake of bone tracers has emerged as useful tool for the early detection of transthyretin amyloidosis ATTR. Oral tafamidis therapy has inhibited the progression of neurological and cardiovascular symptoms this far The authors declare that no patient data appear in this article. Stoppini M, Bellotti V. Cardiacs Mayo Clinic experience from to Thoracic cross-sectional imaging of amyloidosis. Light chain amyloidosis AL and transthyretin TTR amyloid are the two most prevalent forms of this disease that commonly results in cardiac amyloidosis. Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy.
Amiloidose cardíaca: o que você sabe sobre ela?
The median follow-up period was acrdiaca. The authors declare that no patient data appear in this article. Use Read by QxMD to access full text via your institution or open access sources. Pulmonary amyloidosis: computed tomography findings The Mayo Clinic experience from to Novel pharmacotherapies for cardiac amyloidosis. The precursor protein that is produced in excess defines the specific amyloid type. Cardiac involvement often leads to significant morbidity and mortality and increasingly has been recognized as an important cause of heart failure.