Non-amyloid specific treatment for transthyretin cardiac amyloidosis: a clinical consensus statement of the ESC Heart Failure Association
Transthyretin cardiac amyloidosis (ATTR-CM) is a disease in which an abnormal buildup of a protein called transthyretin forms deposits (“amyloid”) is present in the heart. These deposits make the heart stiff and weak, leading to heart failure, arrhythmias, and other complications.
This document by Pablo García Pavía, Esther González López, and colleagues does not focus on disease-specific treatments that slow amyloid buildup, but on all the supportive cardiac treatments needed to manage symptoms and complications—because even with specific therapies, patients still require careful management of heart problems.
This disease (Amyloid deposits) may affect almost all parts of the heart, leading to: Heart failure, Atrial fibrillation and other arrhythmias, electrical conduction disease (which may require pacemakers), risk of blood clots or Aortic stenosis (narrowing of the aortic valve).
There are “non-specific” treatments recommended throughout the manuscript. Firstly, patients with amyloidosis often retain too much fluid, so water pills (diuretics) are the main treatment to relieve swelling and breathing problems, but doctors must be careful not to lower blood pressure too much or harm the kidneys. Patients should keep an eye on their weight, salt and fluid intake, and kidney tests. Some standard heart-failure medications—like mineralocorticoid receptor antagonists and SGLT2 inhibitors (Medicines that help protect the heart and kidneys by helping the body get rid of excess fluid and sugar) —tend to help and are usually well tolerated. Others, like beta-blockers, are rarely used unless the heart-pumping strength is low, and drugs such as ACE inhibitors, ARBs, or sacubitril/valsartan (medicines that help blood vessels relax, lower blood pressure, and help the heart work more efficiently) often cause side effects and are used mainly if high blood pressure needs treatment. In advanced disease, heart transplantation can be a good option, but mechanical heart pumps (LVADs) usually do not work well because the heart is too stiff and small. Atrial fibrillation (irregular heartbeat) requires a personalized approach; many heart-rate–slowing drugs don’t work well, so some patients need a pacemaker after a procedure that blocks the heart’s electrical pathway. Blood thinners are always recommended in atrial fibrillation, no matter the usual risk-score. Electrical conduction problems are common and may require a pacemaker, and if the heart will need pacing most of the time, a special type called CRT is preferred. If the patient also has aortic valve narrowing, a minimally invasive procedure (TAVR) is usually favored over open-heart surgery.
A major message of the document is that high-quality clinical trials are lacking in almost all areas of supportive ATTR-CM care. Most recommendations are based on expert opinion and small observational studies.
Key knowledge gaps include: which heart-failure medications truly improve outcomes, how best to manage arrhythmias, how to predict who will need pacemakers, whether ICDs prevent sudden cardiac death in this population and the optimal management of patients with both ATTR-CM and aortic stenosis
In summary, managing ATTR-CM requires more than amyloid-targeted drugs.
The document offers practical guidance for treating heart failure, arrhythmias, conduction disease, aortic stenosis, and advanced heart-failure needs, while highlighting the urgent need for better research and randomized trials.
Pablo Garcia-Pavia, Esther Gonzalez-Lopez, Lisa J Anderson, Francesco Cappelli, Thibaud Damy, Marianna Fontana, Jose Gonzalez-Costello, Ruxandra Jurcut, Olivier Lairez, Peter van der Meer, Marco Merlo, Stefano Perlini, Antoni Bayes-Genis
Eur Heart J. 2025 Oct 7:ehaf710. doi: 10.1093/eurheartj/ehaf710. Epub ahead of print. PMID: 41055898.
Prepared by Pablo Garcia-Pavia and Ester Costafreda