Quick Dive: Supportive management of ATTR-CM

What is the reason for and aim of the publication?

The rationale for this publication stems from a major unmet need in the management of transthyretin cardiac amyloidosis (ATTR-CM). While disease-modifying therapies targeting the amyloidogenic process have significantly improved prognosis, a large proportion of patients continue to experience heart failure symptoms, arrhythmias, conduction disease, and valvular complications that require non-amyloid specific management.

The primary aim of this consensus statement was to provide practical, evidence-informed guidance on the supportive treatment of ATTR-CM, addressing day-to-day clinical challenges that are not covered by randomized trials or traditional heart failure guidelines. By synthesizing available observational data and expert opinion, the document seeks to harmonize clinical practice, improve symptom control and quality of life, and assist clinicians in navigating complex therapeutic decisions in this increasingly prevalent condition.

What are the most important take-home messages?

1. ATTR-CM requires a tailored approach to heart failure management.
   Volume control with diuretics remains the cornerstone of therapy, but treatment must be individualized due to restrictive physiology, limited preload reserve, and frequent autonomic dysfunction. Over- and under-diuresis are both harmful and require careful monitoring.
2. Conventional guideline-directed heart failure therapies should not be applied indiscriminately.
   Neurohormonal blockers such as beta-blockers and renin–angiotensin system inhibitors are often poorly tolerated and lack robust evidence of benefit. In contrast, mineralocorticoid receptor antagonists and SGLT2 inhibitors appear well tolerated and are associated with improved outcomes in observational studies.
3. Multidisciplinary, proactive management of complications is essential.
   Atrial fibrillation, conduction disease, thromboembolic risk, aortic stenosis, and advanced heart failure require early recognition and disease-specific strategies. Transcatheter aortic valve replacement should not be withheld in patients with concomitant ATTR-CM, and heart transplantation remains a valid option in selected patients.

What are challenges in practical implementation – and possible solutions?

One of the main challenges is the lack of randomized clinical trial data supporting most non-specific therapies in ATTR-CM, which creates uncertainty and heterogeneity in clinical practice. This is compounded by the fact that standard heart failure treatments may worsen symptoms due to hypotension, chronotropic incompetence, or low cardiac output.

Another challenge is the complexity of managing multiple cardiac and extracardiac manifestations simultaneously, often in elderly and frail patients. Limited awareness of ATTR-CM outside specialized centres may also delay diagnosis and appropriate supportive care.

Potential solutions include management within multidisciplinary amyloidosis units, careful patient phenotyping, gradual and closely monitored treatment adjustments, and the use of structured follow-up strategies such as ambulatory diuresis programs, rhythm monitoring, and individualized device selection. Consensus-based documents such as this one help bridge the evidence gap until more robust data become available.

Which issues still need to be tackled, that are not yet addressed by the paper?

Several important questions remain unanswered. There is a clear need for randomized trials evaluating the efficacy and safety of heart failure therapies, rhythm control strategies, and device-based interventions specifically in ATTR-CM. The optimal role of ICDs for primary prevention of sudden cardiac death remains particularly controversial.

In addition, better risk stratification tools are needed to guide anticoagulation in patients in sinus rhythm, predict progression of conduction disease, and identify patients who may benefit most from advanced therapies. The interaction between disease-modifying treatments and supportive therapies also warrants further investigation.

What further developments on the topic are emerging?

The field is evolving rapidly. Improved awareness and earlier diagnosis of ATTR-CM are increasing the number of patients requiring long-term supportive care. Ongoing and planned clinical trials are exploring the role of sacubitril/valsartan, advanced pacing strategies, and novel monitoring technologies in this population.

In parallel, the expanding use of disease-modifying therapies is likely to change the natural history of ATTR-CM, potentially modifying the risk–benefit balance of devices such as ICDs and altering indications for heart transplantation. Future management will increasingly rely on integrated, personalized approaches that combine amyloid-specific treatments with optimized non-specific care.

Non-amyloid specific treatment for transthyretin cardiac amyloidosis

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