What is the management approach for a patient with recurrent syncope and amyloidosis?

From the Guidelines

Management of recurrent syncope in patients with amyloidosis requires a multidisciplinary approach addressing both the underlying amyloidosis and the specific cardiac manifestations causing syncope, with the most recent and highest quality study suggesting a comprehensive approach including disease-specific therapy and careful management of orthostatic hypotension 1.

Key Considerations

• Initial evaluation should include cardiac monitoring, orthostatic vital signs, and comprehensive cardiac assessment with echocardiography, cardiac MRI, and electrophysiology studies to determine the syncope mechanism.
• For cardiac amyloidosis patients, treatment typically involves disease-specific therapy such as tafamidis (61 mg daily) for ATTR amyloidosis or chemotherapy regimens for AL amyloidosis.
• Syncope management includes careful titration of medications that may worsen orthostatic hypotension, volume maintenance with adequate hydration and salt intake, compression stockings, and midodrine (2.5-10 mg three times daily) for orthostatic hypotension.

Disease-Specific Therapy

• Tafamidis (61 mg daily) is recommended for ATTR amyloidosis, as it has been shown to slow disease progression and improve survival 1.
• Chemotherapy regimens, such as bortezomib-based regimens, are recommended for AL amyloidosis, with high-dose melphalan followed by autologous stem cell transplantation offering the possibility of long-lasting remission and high organ response rates in selected patients 1.

Orthostatic Hypotension Management

• Midodrine (2.5-10 mg three times daily) is recommended for orthostatic hypotension, as it can help improve blood pressure and reduce symptoms of syncope.
• Fludrocortisone (0.1-0.2 mg daily) can help with volume expansion in neurogenic orthostatic hypotension, but should be used with caution in patients with cardiac involvement.

Cardiac Complications

• Patients with conduction abnormalities often require permanent pacemaker implantation, while those with ventricular arrhythmias may need an implantable cardioverter-defibrillator.
• Regular follow-up with cardiology and hematology is essential, as is medication adjustment to minimize syncope risk.

From the FDA Drug Label

INDICATIONS AND USAGE VYNDAQEL and VYNDAMAX are transthyretin stabilizers indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. (1) The management approach for a patient with recurrent syncope and amyloidosis may involve treating the underlying cardiomyopathy with transthyretin stabilizers like tafamidis to reduce cardiovascular mortality and cardiovascular-related hospitalization 2.

• The primary goal is to address the amyloidosis-related cardiomyopathy.
• Tafamidis may be considered as part of the management approach.

From the Research

Management Approach for Recurrent Syncope and Amyloidosis

The management approach for a patient with recurrent syncope and amyloidosis involves a comprehensive diagnostic evaluation and treatment strategy.

• The diagnosis of cardiac amyloidosis is usually performed by endomyocardial biopsy, but non-invasive diagnostic methods such as echocardiography play an important role in detecting specific signs of cardiac amyloid infiltration 3.
• Echocardiography can detect thickened right and left ventricular myocardium, normal or small left ventricular cavity size, diffuse hyper-refractile 'granular sparkling' appearance, and 'mismatch' ECG/ECHO, which are specific findings of cardiac amyloidosis 3.
• Cardiac imaging, including bone scintigraphy, echocardiography, and cardiac magnetic resonance imaging, can guide treatment and monitor response to treatment in patients with cardiac amyloidosis 4.
• The treatment approach for cardiac amyloidosis depends on the subtype, with immunoglobulin light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) being the two most commonly encountered subtypes 4.
• Patients with cardiac amyloidosis should be examined by echocardiography, as cardiac involvement is frequently found in patients with no clinical symptoms, and non-symptomatic patients with echocardiographic evidence of cardiac involvement will almost always develop cardiac symptoms 5.
• The prognosis for patients with cardiac amyloidosis is poor, with a median survival time of 36 months from the time of amyloidosis diagnosis, and 23 months from the time of amyloid myocardiopathy diagnosis 5.
• Recurrent syncope in patients with cardiac amyloidosis may be a sign of advanced disease, and prompt diagnosis and treatment are essential to improve outcomes 6, 7.

Diagnostic Evaluation

• A comprehensive diagnostic evaluation, including clinical examination, electrocardiography, echocardiography, and cardiac biopsy, is necessary to diagnose cardiac amyloidosis 6.
• The diagnosis of cardiac amyloidosis can be challenging, and a novel electrocardiogram criterion may assist in the diagnosis of cardiac amyloidosis 7.
• Cardiac imaging can help establish an accurate diagnosis, monitor treatment response, and aid in the adjustment of treatment strategies accordingly 4.

Treatment Strategies

• The treatment approach for cardiac amyloidosis depends on the subtype, and advances in multi-parametric cardiac imaging have resulted in earlier diagnosis and initiation of treatment 4.
• Treatment strategies for cardiac amyloidosis include chemotherapy, targeted therapies, and supportive care, with the goal of improving symptoms and slowing disease progression 4.
• Cardiac transplantation and autologous stem cell transplantation may be considered in selected patients with advanced disease 6.