Adolescents and young adults with obesity and T2DM had higher E/e’ and lower E/A ratios compared to the normal group despite having no LA enlargement. Obese and T2DM subjects were also found to have significantly worse LA function strain of all three LA functional components and significantly worse reservoir and conduit strain rates compared to controls. Atrial strain measures associated with diastolic function abnormalities in obese and T2DM groups.
Although the majority of these diastolic function indices are still within normal range based on the diastolic function guidelines4, our study is novel in demonstrating significant differences in diastolic function starting at a young age. This may imply a trend for further and quicker worsening of diastolic function of the obese and T2DM group if they were followed for a longer period. This theory is supported by studies which have shown childhood adiposity to be independently associated with structural cardiac disturbances,17 as well as abnormalities in LA function in patients with long-standing metabolic syndrome.18 Though not specifically focusing on LA function other studies have shown that adolescents with T2DM have lower E/A ratios.19 In addition, when we used the worst 25th percentile cut point for diastolic function based on the normal subjects in this cohort, a high proportion of obese and T2DM subjects were in the group with abnormal diastolic function. Our study also showed that LA diameter is an insensitive measure for diastolic dysfunction. Our multivariable analysis did not show LA size to be a predictor of diastolic function abnormalities in obese and T2DM patients. Furthermore, the indexed LA volume was significantly larger in the normal group compared to the T2DM and obese groups. This is likely due to the higher body surface area in the latter groups. Thus, LA volume cannot be used to detect early diastolic dysfunction in obese adolescents and young adults as LA enlargement is likely a late sign and may not be accurately perceived when indexed to a relatively large body size.
Additionally, we show that LA strain measures have an independent association with diastolic function abnormalities on multivariate analysis. Obese and T2DM patients have a worse reservoir, conduit and booster strain and worse reservoir and conduit strain rate. This is not surprising since studies in adults have shown that LA strain becomes abnormal over a decade before the LA becomes dilated.20
Epidemiological analysis has linked obesity and T2DM as a risk factor for atrial fibrillation, though an exact mechanism is still unclear, it could be related to atrial function abnormalities.21 In adults reduced LA reservoir and conduit function as well as changes in booster function have been used to predict the onset of paroxysmal atrial fibrillation.22,23 Progression to chronic atrial fibrillation has also been shown to be closely related to LA reservoir strain.24 Similarly, measures of LA function and strain have been shown to improve following ablation for atrial fibrillation with return of normal sinus rhythm.25 Furthermore, LA reservoir strain has been shown to be a better predictor of elevated left ventricle end-diastolic pressure than average E/e’ ratios.26,27 In patients with normal LA size, studies have shown that reduced reservoir strain was a predictor of developing NYHA class II and IV symptoms within two years and had good correlation with pulmonary capillary wedge pressure.27,28 Despite these benefits of measuring LA functional parameters many practitioners may be more comfortable using LV GLS as a reliable method of LV diastolic function. We are not suggesting LA function measurements should replace LV GLS, but rather that LA function measurements act as a complementary measurement, which may be able to detect LV diastolic dysfunction earlier than LV GLS.
The Strong Heart Study showed that the presence of diabetes mellitus alone is a risk factor for the development of abnormal atrial function.29 Studies by Di Salvo et al. showed that obesity (even with normal blood pressure) in the pre and early pubertal children was associated with abnormal atrial strain.30 Although the majority of the patients in our study had normal blood pressure, early-onset hypertension has been associated with adverse LA remodeling.31 Similar studies conducted in adult patients followed longitudinally concluded that obesity is associated with impaired reservoir and conduit function,32 and that obesity, regardless of the presence of T2DM is associated with abnormal LV global longitudinal strain.33 In our study, we showed that abnormal diastolic function measures and LA function were already present in many of the obese and T2DM patients at a young age. Therefore, one could postulate that adolescents and young adults with obesity and T2DM are at risk to develop abnormal left atrial function earlier than normal weight patients. Regardless of etiology, there appears to be a common pathway to atrial dysfunction. In early stages there is a decrease in reservoir and conduit function with a compensatory increase in contractile (booster pump) function.5,8,31 Our study also suggests this to be true as the booster strain rate was not different between the groups, possibly because of their young age. In the more advanced phase of diastolic dysfunction which often coincides with the onset of heart failure symptoms, there is additionally a decrease in contractile function resulting in lower booster strain with further decrease in reservoir and conduit function.32
An important question is whether T2DM in this population adds deleterious role in diastolic function compared to obesity. In our study, the T2DM patients had significantly higher E/e’ and lower E/A ratios compared to the obese group and as mentioned were more likely to be in the percentile group trending towards abnormal diastolic function. However, blood pressure, LV mass, and atrial strain and strain rates were not different between the two groups. This may indicate that at this early age T2DM does not compound the cardiac remodeling associated with obesity, but further studies would be needed to better assess this.
One factor that may improve diastolic dysfunction in T2DM is the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i). Multiple studies have shown improvement in LV diastolic function within 3 months of therapy.34,35 These studies assessed the effect of these medications and found improvement in E/e’ in patients prescribed SGLT2i. LA function parameters were not specifically assessed in these studies but would be an interesting focus of future analysis.
A major concern for using LA function as a reliable assessment of diastolic function is the inter and intra observer variability. It is important to note, that echocardiography is a reliable method to assess LA functional parameters.36 In our study the initial LA measurements were reanalyzed by multiple imaging trained pediatric cardiologists with no significant discrepancies.
These aforementioned studies are important for children and young adults such as those in our study population, who currently are asymptomatic but considered at higher risk for development of atrial fibrillation and diastolic heart failure. Clinically, the implications of our study are relevant, even in the absence of longitudinal follow up data due to the noted literature of the negative effects of obesity and T2DM on diastolic function in adults.32,18,19,33 Thus, pediatric and adult cardiologists can expect progression to abnormal diastolic function and LA functional data may aid efforts for early detection of diastolic function abnormalities in this young patient population. From a practical standpoint, this information may help inform the patients and families about the adverse effects of obesity on the cardiovascular system.