Study Population

In this prospective, observational cohort study, we recruited patients from a large community-based study in Australia, which had the primary objective of early detection of HF in the community. Asymptomatic participants ≥65 years of age were recruited if they had one or more risk factors, including hypertension (systolic blood pressure > 140 mm Hg or preexisting use of antihypertensive medications), type 2 diabetes mellitus (on the basis of self-report of diagnosis or the current use of diabetic medications), and obesity (defined as body mass index ≥ 30 kg/m ² ). Exclusion criteria were (1) inability to provide written consent to participate in the study, (2) history of moderate or greater valvular disease, (3) known history of HF, (4) reduced LV systolic function on baseline echocardiography (LV ejection fraction < 40%), (5) contraindications to β-blockers and angiotensin-converting enzyme inhibitors, (6) life expectancy < 1 year, and (7) inability to perform strain analysis or acquire interpretable images from baseline echocardiography. All patients with known histories of AF or documented AF on baseline electrocardiography were excluded from the study. All patients were provided written informed consent, and approval was obtained from the institution’s human research ethics committee.

Clinical Findings

All participants undertook a clinical history and answered questionnaires to assess overall health status at the start of the study. Information regarding demographics, medical history, medication history, and baseline examination data (height, weight, body mass index, and blood pressure) was recorded for all participants. Baseline electrocardiography and echocardiography were conducted in all participants.

Echocardiography

All echocardiographic examinations were performed by qualified sonographers using the same equipment (Siemens Acuson SC2000, Siemens Medical Solutions USA, Mountain View, CA) and transducers (4V1c [1.25–4.5 MHz] and 4Z1c [1.5–3.5 MHz]). Two-dimensional, M-mode, and Doppler measures were obtained using standard techniques outlined by the American Society of Echocardiography. LV dimensions were calculated in both diastole and systole in parasternal long-axis views. LV hypertrophy was defined as LV mass index > 115 g/m ² in men and >95 g/m ² in women. LV and LA volumes were indexed to body surface area and calculated using the Simpson biplane method. Abnormal LA volume index was defined as ≥34 mL/m ² .

Diastolic function was assessed by calculating mitral inflow peak early and late diastolic velocities (E and A waves, respectively), deceleration time, and the E/A ratio (a ratio < 0.8 was used to define impaired relaxation). Mitral annular early diastolic velocity using Doppler tissue imaging (e′) was calculated in both septal and lateral and averaged to calculate the E/e′ ratio (>13 was used to define increased LA filling pressures).

GLS was calculated in the apical four-chamber view, and global circumferential strain (GCS) was calculated in the mid-LV parasternal short-axis view. Velocity Vector Imaging was used to assess ventricular strain. Manual tracing of the endocardial border of the left ventricle was performed in end-systole, and this was tracked during the cardiac cycle. LA reservoir, conduit, and pump strain was assessed using speckle-tracking imaging by an external third-party software program (Image Arena; TomTec Imaging Systems, Munich, Germany). Apical four- and two-chamber images were selected with a frame rate of 60 to 80 frames/sec. The endocardial border of the left atrium was manually traced, and strain analysis was performed using the LV strain algorithm, with the average of both the four- and two-chamber values. The reference point for image analysis was taken at the onset of the QRS complex (R-R gating; Figure 1 ). Patients with poor image quality, such that strain analysis could not be performed, were excluded. All strain measurements were performed by two investigators. Reproducibility was assessed using a random sample of 20 patients, and the mean percentage difference was calculated.

Components of LA strain.

HF Follow-Up

All participants were followed using questionnaires, phone calls, and follow-up clinical visits at a median time of 12 months (interquartile range, 6 months). HF symptoms were assessed using the Framingham criteria. We included patients with HF with reduced ejection fraction and those with HF with preserved ejection fraction, per criteria outlined by the European Society of Cardiology. All patients were reviewed by a cardiologist in the clinic, and information was collected regarding symptoms and examination findings. Patients underwent echocardiography to confirm the presence of HF.

Statistical Analysis

Patients were split into two groups on the basis of GLS (cutoff −18%) and GCS (cutoff −22%). All categorical variables are presented as frequencies and percentages, and continuous variables are presented as mean ± SD (if normally distributed) or as medians and interquartile ranges (if nonparametric). Statistical significance was assessed using the χ ² test for categorical data and the independent-sample t test for continuous data. Simple linear regression was used to identify associations between LV function and clinical parameters with LA reservoir, conduit, and pump strain. All variables with P values < .10 in univariate analyses were considered in multivariate regression models. Cox proportional-hazard models were used to assess for the association between LA strain and incident HF. Analyses were considered to be statistically significant if two-tailed P values were <.05. Statistical analysis was performed using SPSS version 22 (SPSS, Chicago, IL).

Baseline Characteristics

A total of 576 patients were included in the study (mean age, 70.7 ± 4.7 years; 46% men). The majority of patients had type 2 diabetes mellitus (52%), obesity (43%), hypercholesterolemia (54%), and hypertension (79%). Mean values of LA reservoir, conduit, and pump strain were 39.3 ± 6.8%, 19.8 ± 5.4%, and 19.4 ± 5.0%, respectively. A summary of baseline patient characteristics is shown in Table 1 .

Associations of Impaired LV Strain

Participants were split into two groups on the basis of GLS (normal, ≤−18%; n = 352). Table 2 shows that patients with abnormal GLS were older, were more likely to be male, hypertensive, and obese, and were more likely to have diabetes mellitus. LA reservoir and conduit strain was reduced in the group with abnormal GLS (reservoir strain, 38.2 ± 7.3% vs 39.9 ± 6.4% [ P = .004]; conduit strain, 18.7 ± 5.7% vs 20.5 ± 5.1% [ P < .001]). There were no significant differences with regard to LA pump strain (19.5 ± 5.5% vs 19.3 ± 4.7%, P = .72).

Participants were also split into two groups on the basis of GCS (normal, ≤−22% [ n = 533]; abnormal, >−22% [ n = 43]) ( Table 3 ). Patients with abnormal GCS were more likely to be male and to have higher body mass index and rates of diabetes mellitus and ischemic heart disease ( P < .05). Groups were not different with respect to LA reservoir (39.3 ± 6.8% vs 39.0 ± 7.3%, P = .83), conduit (19.9 ± 5.3% vs 19.0 ± 6.5%, P = .30), and pump (19.4 ± 5.0% vs 20.0 ± 5.3%, P = .38) strain.

Associations of LA and LV Function

LA reservoir strain was independently associated with GLS ( r = 0.16, β = −0.13, P = .001). GCS was not associated with reservoir strain. LA reservoir strain was associated with E/e′ ratio ( r = 0.16, β = −0.12, P = .004) and LV mass ( r = 0.14, β = −0.09, P = .03) independent of age ( r = 0.26, β = −0.21, P < .001). It was not associated with A wave or deceleration time ( P > .05) ( Table 3 ).

LA conduit strain was independently associated with GLS ( r = 0.21, β = −0.14, P = .01). GCS was not independently associated with conduit strain. LA conduit strain was associated with E wave ( r = 0.14, β = 0.21, P < .001) and A wave ( r = 0.11, β = −0.19, P < .001), independent of age ( r = 0.23, β = −0.18, P < .001). It was not associated with deceleration time or LV mass ( P > .05) ( Table 4 ).

Table 4

Associations between atrial conduit strain and LV mechanics and diastolic dysfunction

Variable	Univariate			Multivariate
	Unstandardized coefficient (95% CI)	Standardized β	P	Unstandardized coefficient (95% CI)	Standardized β	P
Age	−0.27 (−0.36 to −0.17)	−0.23	<.001	−0.21 (−0.30 to −0.11)	−0.18	<.001
GLS	−0.44 (−0.62 to −0.27)	−0.21	<.001	−0.31 (−0.48 to −0.13)	−0.14	.001
GCS	−0.08 (−0.16 to 0.002)	−0.08	.06	−0.02 (−0.10 to 0.06)	−0.02	.57
E/e′ ratio	−0.28 (−0.45 to −0.11)	−0.13	.001	−0.31 (−0.52 to −0.10)
E wave	4.9 (2.1 to 7.7)	0.14	.001	7.1 (4.0 to 10.2)	0.21	<.001
A wave	−3.3 (−5.6 to −0.92)	−0.11	.007	−5.5 (−8.1 to −3.0)	−0.19	<.001
Deceleration time	−0.01 (−0.02 to 0.002)	−0.06	.15
LV mass index	−0.02 (−0.04 to 0.0)	−0.08	.05	−0.01 (−0.03 to 0.01)	−0.04	.36

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