"Cardiac Amyloidosis in Heart Failure: Advances in Diagnosis, Treatment, and Patient Management"

 Cardiac amyloidosis is increasingly recognized as a cause of heart failure (HF).

Most cases are classified as either light-chain amyloidosis (AL) or transthyretin amyloidosis with cardiomyopathy (ATTR-CM).

Advances in Diagnosis
Newer imaging techniques enable accurate noninvasive diagnosis of ATTR-CM.
Early diagnosis is critical due to the availability of effective therapeutic agents.

Case Presentation
A hypothetical 75-year-old man with HFpEF, atrial fibrillation (AFib), and chronic kidney disease (CKD) presents with multiple hospitalizations.
His echocardiogram reveals left ventricular hypertrophy (LVH) and conduction disease without systemic hypertension.

Challenges in Diagnosis
Patients often see multiple providers before a diagnosis of cardiac amyloidosis.
Less than half of patients receive a diagnosis within six months of symptom onset.

Diagnostic Clues
Older patients with HFpEF, AFib, and CKD may have cardiac amyloidosis.
Clinical clues include LVH, conduction disease, and non-hypertensive heart failure.

Next Steps in Evaluation
First, rule out AL amyloidosis using serum kappa/lambda light chains and immunofluorescence.
If monoclonal proteins are absent, proceed with Tc-PYP cardiac scintigraphy.
Further, genetic testing can differentiate between hereditary ATTR and wild-type ATTR.

Emerging Therapies
Tafamadis stabilizes transthyretin protein and reduces mortality and hospitalizations.
Despite its benefits, access to tafamadis can be limited due to high costs.
Patisiran, a TTR silencer, preserves functional capacity but is not FDA-approved for cardiomyopathy.
Vutrisiran, studied in the HELIOS-B trial, shows promise in reducing cardiovascular events.
Future therapies include antibodies and CRISPR gene editing technologies.

Heart Transplantation
Patients with advanced cardiac amyloidosis may be candidates for heart transplantation.
Extra-cardiac manifestations like frailty and proteinuria must be evaluated for transplant eligibility.
Post-transplant outcomes for amyloid cardiomyopathy are comparable to other indications with careful patient selection.
Continuation of disease-directed therapies post-transplant is recommended.

Take-Home Points

1. Cardiac amyloidosis is a significant cause of heart failure, often underdiagnosed.
2. New diagnostic techniques enable early and accurate identification.
3. Rule out AL amyloidosis before proceeding with tests for ATTR-CM.
4. Tafamadis and other emerging treatments improve outcomes but face accessibility challenges.
5. Heart transplantation remains a viable option for select patients with advanced disease.
6. Multidisciplinary care and early diagnosis are key to improving patient outcomes.