Cardioembolic strokes, which account for about 25% of ischemic strokes, are classically thought to arise when atrial fibrillation and structural abnormality or dilatation of the left atrium (LA) result in blood stasis and thrombus formation. However, aging can cause remodeling of cardiac chambers, and enlargement of the LA is a well-established risk factor for adverse cardiovascular events.

Brigham and Women’s Hospital researchers have demonstrated that in an older population with normal ejection fraction and sinus rhythm, age‐related LA reservoir dysfunction and stiffness—detectable on three-dimensional echocardiography (3DE)—were associated with higher odds of subclinical cerebral infarcts (SCIs) and stroke. Francesco Bianco, MD, PhD, formerly of the Division of Cardiovascular Medicine at the Brigham, Scott D. Solomon, MD, the Edward D. Frohlich Distinguished chair and director of the Clinical Trials Outcomes Center at the Brigham, and colleagues present their findings in the Journal of the American Heart Association.

Methods

The researchers used data from the ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study). From 1987 to 1989, ARIC investigators enrolled and examined 15,792 men and women ages 45 to 64 in four U.S. communities. Follow-up is ongoing.

The 407 participants selected for this analysis underwent 3DE at study visit 5, between 2011 and 2013. At the time, all were in sinus rhythm, without a history of atrial fibrillation or flutter, and with normal ejection fraction (≥50%). 60% of participants were women, the mean age was 76, and 21% were Black.

The team analyzed the sample across tertiles of age:

• Tertile 1—Mean age 68 (n=136)
• Tertile 2—Mean age 76 (n=136)
• Tertile 3—Mean age 83 (n=135)

Participants were also categorized into three groups by outcomes:

• No SCI—No cerebral infarcts on brain MRI scans and no clinical history of stroke (n=315)
• SCI—No clinical history of ischemic stroke but MRI evidence of SCI (n=58)
• Stroke—Both clinical history of ischemic stroke and MRI evidence of SCI (n=34)

LA Structural and Functional Characteristics

3DE parameters changed with age:

• LA global longitudinal strain, an index of LA reservoir function—decreased across age tertiles (P for trend, 0.014) and worsened in the SCI and stroke groups (P for trend, <0.001 and 0.045, respectively)

• Mitral E/e’ ratio divided by LA global longitudinal strain, an index of LA stiffness—increased across age tertiles (P for trend, 0.001) and was progressively impaired in the SCI and stroke groups (P for trend, 0.001 and 0.011, respectively)

No differences in these measures by age were found in the group without SCI.

Outcome Analysis

After adjustments for potential confounders, LA reservoir function and stiffness significantly worsened across the spectrum of cerebral thromboembolism:

LA global longitudinal strain (LA reservoir function)

• Negatively associated with increased odds of SCI and stroke in all age tertiles

• A significant interaction between age tertiles for SCI (P for interaction, 0.043) and stroke (P for interaction, 0.010)

Mitral E/e’ ratio divided by LA global longitudinal strain (LA stiffness)

• Positively associated with SCI and stroke in all age tertiles

• A significant interaction between age tertiles for SCI (P for interaction, 0.040)

Early Assessment May Be Worthwhile

These findings suggest that independently from atrial fibrillation and reduced ejection fraction, LA senescence can result in clot formation that leads to SCIs and, later, clinically apparent stroke.

Routine assessment of LA global longitudinal strain in older individuals may be worthwhile to detect subclinical atrial dysfunction and guide anticoagulation therapy, even in the absence of atrial fibrillation.