Assessment of left atrial function: Another window to detect early cardiac impairment?

The article by Tadic and colleagues1 in this issue of the Journal draws attention to the importance of identifying early evidence for cardiac involvement in hypertension.

The most common structural alteration of the left atrium is left atrial (LA) enlargement, which has been considered a biomarker for adverse cardiovascular outcomes, especially in patients with left ventricular (LV) diastolic dysfunction and atrial fibrillation.1 In the literature, LA function is related to cardiovascular and overall mortality, although there is still no consensus on the association.3 Our understanding of LA function is evolving with the deepening of investigations, and it is believed that LA function may play an important role in the future management of cardiovascular diseases.

The principal function of the left atrium is to modulate LV filling and cardiovascular performance. Generally, LA has three functions in a cardiac circle. First, it acts as a reservoir that receives blood from the pulmonary veins during ventricular systole. Second, it acts as a conduit that passively transfers blood into the left ventricle during early ventricular diastole. Third, it also acts as a booster pump that actively contracts during late ventricular diastole. LA size and function can be assessed by echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging. In clinical practice, echocardiography is the most common assessment tool, because of its simplicity, safety, and ability to image in real time with high temporal resolution. Normally, LA function is assessed using two‐dimensional echocardiography through volumetric analysis, spectral Doppler, tissue Doppler, strain, and strain rate imaging. However, two‐dimensional echocardiography measurement has its own limitations, such as inaccuracies caused by geometric assumption and foreshortening of the left atrium. In this condition, three‐dimensional echocardiography emerged with the ability to overcome these limitations. Preliminary data show that three‐dimensional echocardiography can more accurately assess LA function.2, 3 With the gradual improvement of the three‐dimensional echocardiography technique in clinical application, more accurate LA evaluation will be acquired, which will expand the comprehensive recognition of LA function and further reveal its significance.

LA function is highly influenced by LV diastolic function due to the left atrium being directly exposed to the pressure from the left ventricle, especially in diastole. When LV diastolic dysfunction occurs, the LA pressure increases to overcome the diastolic intraventricular pressure and to ensure adequate LV filling through modulating LA functions of reservoir, conduit, and booster pump. As an important cause of LV diastolic dysfunction, hypertension may also influence LA function. The evaluation of LA function in patients with hypertension has shown that booster pump function of the left atrium increases but conduit function decreases, as compared with patients with normotension.4, 5, 6, 7 However, further investigation is needed to explore the relationship between LA function and hypertension and to verify whether LA dysfunction is also an important sign of hypertensive organ damage similar to LV diastolic dysfunction.

The application of ambulatory blood pressure (BP) monitoring has expanded a new era, with some emerging BP measurements, such as BP circadian variation and average nighttime BP. Abnormal BP circadian variation, reflected by nondipper status, is defined as a drop in nighttime BP <10% of the mean daytime BP. It is demonstrated that patients with nondipper status have a worse prognosis in terms of cardiovascular diseases and have more hypertensive organ damage, such as LV hypertrophy and diastolic dysfunction.8, 9, 10 Recently, several studies reported that nondipper status was also associated with LA functional alteration.4, 11 Similar to nondipper status, the average nighttime BP has also been shown to be associated with cardiovascular subclinical organ damage and events.12 Moreover, average nighttime BP has been suggested to be superior to average daytime BP in terms of prognostic significance.13, 14 A recent study showed that patients with normal daytime BP but abnormal nighttime BP presented high risk of mortality.15 A new term called isolated nocturnal hypertension was proposed to emphasize the importance of the significance of the nighttime BP level. Nondipper status is associated with high nighttime BP and may accompany nocturnal hypertension; however, they are not always present together. A recent study showed that, in the presence of nocturnal hypertension, nondippers had similar organ damage as dippers.16 Another recent study indicated that nocturnal hypertension other than nondipper status was independently associated with LV mass index.17 It seems that the significance of nondipper status and nocturnal hypertension is different. Whether nocturnal hypertension is associated with LA function and whether a difference exists between nondipper status and nocturnal hypertension in relation to LA function are still unclear.

In the present issue of the Journal, Tadic and colleagues explored the relationship between hypertensive phenotypes and LA function evaluated by volumetric and strain methods in patients with untreated hypertension free of other cardiovascular risk factors. According to cutoff values of daytime BP of 135/85 mm Hg and nighttime BP of 120/70 mm Hg, 236 patients were divided into four groups, namely day‐nighttime normotension, isolated daytime hypertension, isolated nighttime hypertension, and day‐nighttime hypertension. They found that total LA emptying fraction, an indicator of reservoir function, was significantly lower in patients with isolated nocturnal hypertension and day‐nighttime hypertension than in patients with day‐nighttime normotension and isolated daytime hypertension. Passive LA emptying fraction, an indicator of conduit function, gradually decreased from patients with day‐nighttime normotension, across patients with isolated daytime hypertension and isolated nocturnal hypertension, to patients with day‐nighttime hypertension. All LA strain parameters were significantly deteriorated in the patients with day‐nighttime hypertension than in the patients with normotension and daytime hypertension, and were worse in the patients with nighttime hypertension than in those with normotension. In multiple logistic regression analysis, both isolated nighttime hypertension and day‐nighttime hypertension were associated with reduced total LA emptying fraction and passive LA emptying fraction independently of 24‐hour systolic BP, LV diastolic function, and LV mass index and other confounders. After adjustment, parameters of strain analysis did not show an association with phenotypes of hypertension.

On the basis of a relatively small sample size and moderate level of evidence, Tadic and colleagues indicated that LA function evaluated by volumetric and strain methods was significantly lower in patients with nighttime and day‐nighttime hypertension than in patients with normotension and daytime hypertension. In addition, nighttime and day‐nighttime hypertensions were the independent influencing factors of LA dysfunction. This is the first report on the relationship between LA function and nocturnal hypertension, subsequent to the research on the association of LA function with hypertension defined by office BP and with BP circadian pattern (nondipper status). These findings may have influences on the following aspects: First, it provides additional evidence for the superiority of nighttime BP in relation to subclinical organ damage and adds a new dimension for revealing the mechanisms of the superiority of nighttime BP in predicting cardiovascular risk. Second, it implies the important role of abnormal BP, especially average nighttime BP, on LA function alteration. LA dysfunction may be a sign of asymptomatic target organ damage of hypertension, which is not identified because of limited data and the inaccuracy of assessment of LA function. Future investigations should focus on the influence of high BP, especially nighttime BP, on LA function and explore the corresponding mechanisms.

LA size has been considered a biomarker for adverse cardiovascular outcomes, whereas the significance of LA function is not well recognized, partially because of the limitations of the measuring technique on LA function. Usually, LA size is recognized as a surrogate marker of LA function in clinical practice. However, LA functional impairment is detected in patients who have normal LA size,18 which suggests that LA functional impairment may happen earlier than LA structural abnormality and may provide information of earlier cardiac impairment than LA size alterations do. Currently, it is possible to detect the early abnormalities of LA function that could not be previously measured by conventional assessments.18, 19 Thus, assessment of LA function may be a new window to detect early cardiac impairment in the future, although large efforts and further investigations are warranted.

CONFLICT OF INTEREST

The authors have no conflicts of interest to declare.

Yu S, Zhang Y. Assessment of left atrial function: Another window to detect early cardiac impairment? J Clin Hypertens. 2017;19:1105–1107. 10.1111/jch.13109