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Atrial Mechanical Contraction Predicts Cerebrovascular Risk in Patients With Transthyretin Amyloid Cardiomyopathy and
Aldostefano Porcari1, Beatrice Dal Passo2, Lucia Venneri3
1National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital, London, United Kingdom; Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, Trieste, Italy; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Trieste, Italy.
Insights
Transthyretin amyloid cardiomyopathy patients in sinus rhythm with left atrial dysfunction face high risks of stroke and atrial fibrillation. Left atrial strain analysis can identify high-risk patients for closer monitoring or anticoagulation.
Area of Science:
- Cardiology
- Neurology
- Medical Diagnostics
Background:
- Transthyretin amyloid cardiomyopathy (ATTR-CM) patients in sinus rhythm (SR) are at significant risk for cerebrovascular events.
- Many ATTR-CM patients at risk remain undiagnosed, highlighting a need for improved risk stratification.
Purpose of the Study:
- To identify patients with ATTR-CM in SR who are at high risk of cerebrovascular events.
- To evaluate the role of left atrial (LA) function, specifically atrial electromechanical dissociation (AEMD) and left atrial strain contraction (LASc), in predicting cerebrovascular events and atrial fibrillation (AF).
Main Methods:
- Analysis of 2,310 ATTR-CM patients diagnosed between 2003-2023.
- Assessment of LA function using speckle-tracking strain echocardiography to define AEMD (SR with absent LASc).
- Stratification of patients in SR based on LASc tertiles, with cerebrovascular events (stroke/TIA) and AF development as outcomes.
Main Results:
- Among 873 ATTR-CM patients in SR, 13.2% had AEMD. Over 34 months, 9.7% experienced stroke/TIA and 30.8% developed AF.
- AEMD was independently associated with a 2.4-fold higher risk of incident AF and a 3-fold higher risk of stroke/TIA compared to SR with LA mechanical contraction.
- Severely impaired LASc (<4%) was associated with a 10-fold increased risk of stroke/TIA compared to LASc >7%, significantly improving risk reclassification when added to existing risk scores.
Conclusions:
- Left atrial dysfunction, including AEMD and impaired LASc, is a significant predictor of cerebrovascular events in ATTR-CM patients in SR.
- Left atrial strain analysis offers a valuable tool for refining risk stratification in ATTR-CM patients.
- Identifying high-risk individuals may guide decisions on intensified monitoring or prophylactic anticoagulation.
Background:
Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remain at risk of cerebrovascular events even when in sinus rhythm (SR), yet the majority of these patients are unrecognized.
Objectives:
This study sought to identify patients in SR at high risk of cerebrovascular events.
Methods:
We analyzed patients diagnosed with ATTR-CM between January 2003 and December 2023 at the UK National Amyloidosis Centre. Left atrial (LA) function was assessed using speckle-tracking strain echocardiography. Atrial electromechanical dissociation (AEMD) was defined as SR on electrocardiogram with absent left atrial strain contraction (LASc). Patients in SR were stratified according to LASc tertiles. The primary outcome was a cerebrovascular event defined as stroke or transient ischemic attack (TIA), whichever occurred first. The secondary outcome was development of atrial fibrillation (AF). Death was treated as a competing event.
Results:
The study comprised 2,310 patients with ATTR-CM, of which 873 patients were in SR and not receiving anticoagulation (age 77 years, 82% male, 61% wild type, CHA2DS2-VASc 4). AEMD was present in 115 patients (13.2%). Of the patients in SR, over a median of 34 months (Q1-Q3: 18-54 months), 269 patients (30.8%) developed incident AF and 85 (9.7%) experienced stroke/TIA. Patients with baseline AF receiving anticoagulation had a rate of stroke or TIA of 0.7 per 100 person-years. AEMD was associated with a 2.4-fold higher incident AF and 3-fold higher risk of stroke or TIA compared with SR with LA mechanical contraction (8.7 vs 2.5 per 100 person-years, respectively, for stroke or TIA), independent of CHA2DS2-based scores and markers of disease severity. Among 758 patients in SR without AEMD, LASc tertiles (<4%, 4%-7%, >7%) exhibited an independent association with 1-year risk of stroke or TIA, with LASc <4% being associated with 10-fold increased risk compared to LASc >7%. This association was consistent after adjustment for NAC stage and prior cerebrovascular events. Adding LASc tertiles to CHA2DS2-VASc or CHA2DS2-VA significantly improved model fit and risk reclassification at 1 year.
Conclusions:
LA dysfunction, particularly AEMD and severely impaired LASc, is associated with increased cerebrovascular events in ATTR-CM. Using LAS analysis may refine risk stratification and help identify patients with ATTR-CM in SR who might potentially benefit from intensified extended rhythm monitoring or prophylactic anticoagulation.
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