What are the treatment and follow-up recommendations for a patient with cardiac amyloidosis?

Treatment and Follow-Up for Cardiac Amyloidosis

Disease-Modifying Therapy by Amyloid Type

For ATTR cardiac amyloidosis (both wild-type and hereditary variant), tafamidis is the FDA-approved disease-modifying therapy that reduces cardiovascular mortality and cardiovascular-related hospitalization, and should be initiated in patients with NYHA class I-III heart failure symptoms. 1, 2

ATTR-CM Treatment Protocol

• Tafamidis dosing: Either VYNDAQEL 80 mg (four 20-mg tafamidis meglumine capsules) orally once daily OR VYNDAMAX 61 mg (one 61-mg tafamidis capsule) orally once daily—these formulations are NOT substitutable on a per-mg basis 2

• Capsules must be swallowed whole and not crushed or cut; if a dose is missed, take as soon as remembered or skip and resume regular schedule (do not double dose) 2

• After confirming ATTR-CM diagnosis, perform TTR gene sequencing to differentiate hereditary variant from wild-type disease, as this affects long-term management and family screening 1

AL Cardiac Amyloidosis Treatment Protocol

• First-line therapy: Daratumumab plus CyBorD (cyclophosphamide, bortezomib, dexamethasone) is the standard of care for newly diagnosed AL cardiac amyloidosis, achieving very good partial responses or better in 78.5% of patients 3

• For severe cardiac involvement: Use single-agent daratumumab with minimal dexamethasone to minimize cardiotoxicity risk 3

• Autologous stem cell transplantation: Consider high-dose melphalan followed by autologous SCT for highly selected patients with EF ≥40%, ability to tolerate fluid shifts, and bone marrow plasma cells >10%—complete responders achieve median survival exceeding 15 years 3

Heart Failure Management

Diuretics and Volume Management

• Diuretics are the mainstay of symptomatic heart failure management, but use cautiously to avoid hypotension due to the restrictive physiology and dependence on preload 3

• Monitor closely for orthostatic hypotension and adjust doses carefully as patients are exquisitely sensitive to volume depletion 1

Anticoagulation Strategy

• Anticoagulation is reasonable for ALL patients with cardiac amyloidosis and atrial fibrillation, regardless of CHA₂DS₂-VASc score, due to high thromboembolic risk from atrial stasis 1

• Use warfarin or direct thrombin inhibitors; consider anticoagulation even in patients with history of embolic stroke without documented AF 3

Critical Medications to AVOID

• NEVER use digoxin in cardiac amyloidosis—it binds to amyloid fibrils causing toxicity even at normal serum levels 3, 4

• AVOID calcium channel blockers—they bind to amyloid fibrils causing exaggerated hypotension and negative inotropy 3, 4

• Exercise caution with ACE inhibitors and beta-blockers as they are often poorly tolerated due to restrictive physiology and propensity for hypotension 5

Monitoring Treatment Response

For AL Cardiac Amyloidosis

• Hematologic response monitoring: Measure serum free light chains, serum and urine immunofixation electrophoresis 3

  • Complete response = absence of amyloidogenic light chains
  • Very good partial response and partial response thresholds guide therapy adjustments 3

• Cardiac response criteria: Decrease in NT-proBNP by >30% AND <300 ng/L (if baseline NT-proBNP >650 ng/L) 3

• Serial monitoring schedule: NT-proBNP and troponin measurements, echocardiography, and serum free light chains at regular intervals 3

For ATTR Cardiac Amyloidosis

• Monitor NT-proBNP and troponin levels as prognostic biomarkers 3

• Serial echocardiography to assess left ventricular wall thickness, ejection fraction, and longitudinal strain patterns 6

• Cardiac MRI may be useful for assessing extent of cardiac involvement and tracking disease progression using late gadolinium enhancement patterns and extracellular volume measurements 6

• Monitor for disease-related complications including conduction abnormalities requiring pacemaker consideration 1

Advanced Therapies and Referral Indications

• Refer to advanced heart failure center when patients develop NYHA class IV symptoms or refractory heart failure despite optimal medical therapy 1

• Heart transplantation: Consider for end-stage cardiac amyloidosis, particularly in AL amyloidosis after achieving hematologic remission 5

• Combined heart-liver transplantation: Consider for hereditary ATTR amyloidosis with 5-year survival rates of 50-80% 3

• Pacemaker implantation is frequently required for conduction abnormalities that commonly develop in cardiac amyloidosis 7

Common Pitfalls to Avoid

• Do not delay disease-specific therapy while optimizing heart failure management—early initiation of tafamidis for ATTR-CM or chemotherapy for AL amyloidosis is critical 1, 3

• Do not assume all patients with monoclonal gammopathy have AL amyloidosis—ATTR-CM can coexist with incidental monoclonal proteins, particularly in elderly patients 4

• Avoid aggressive diuresis that can precipitate hypotension and renal dysfunction due to the restrictive physiology 1

• Do not use standard heart failure medications (ACE inhibitors, beta-blockers, calcium channel blockers) without careful consideration of hemodynamic tolerance 3, 5

Multidisciplinary Care Coordination

• Active collaboration between hematologist-oncologist and cardiologist is critical for AL amyloidosis treatment success 5

• Gastroenterology consultation for GI symptoms (common in amyloidosis): dietary modifications including small evening meals, longer intervals between dinner and lying down, low-FODMAP diet for cramping and diarrhea 1

• Neurology involvement for autonomic and sensory polyneuropathy management 1

• Referral to expert amyloidosis center is often necessary for timely diagnosis, treatment initiation, and access to clinical trials 5