Normal Ranges of Left Atrial Strain by Speckle-Tracking Echocardiography: A Systematic Review and Meta-Analysis




Background


Recent advances in the assessment of myocardial function have facilitated the direct measurement of atrial function using speckle-tracking echocardiography. Currently, normal reference ranges for atrial function using speckle-tracking echocardiography are based on a few initial studies, with variations among modestly sized ( n = 100–350) studies.


Methods


The authors searched the PubMed, Embase, and Scopus databases for the key terms “left atrial/atrial/atrium” and “strain/function/deformation/stiffness” and “speckle tracking/Velocity Vector Imaging/edge tracking.” Studies of global left atrial function using speckle-tracking were selected if they involved >30 normal or healthy participants without any cardiac risk factors. Normal ranges for reservoir strain, conduit strain, and contractile strain were computed using a random-effects model. Meta-regression and subgroup analysis was performed to explore between-study heterogeneity.


Results


Forty studies (2,542 healthy subjects) satisfied the inclusion criteria. Meta-analysis revealed a normal reference range for reservoir strain of 39% (95% CI, 38%–41%, from 40 articles), for conduit strain of 23% (95% CI, 21%–25%, from 14 articles), and for contractile strain of 17% (95% CI, 16%–19%, from 18 articles). Meta-regression identified heart rate ( P = .02) and body surface area ( P = .003) as contributors to this heterogeneity. Subgroup analyses revealed heterogeneity due to sample size ( n > 100 vs N < 100, P = .02).


Conclusions


The normal reference ranges for the three components of left atrial function are demonstrated. The between-study heterogeneity is explained partly by heart rate, body surface area, and sample size.


The left atrium contributes to cardiac hemodynamics by modulating left ventricular (LV) filling through the interplay of atrial reservoir, conduit, and booster contractile function. Left atrial (LA) function has been assessed from pressure-volume curves via invasive assessment. The noninvasive assessment of LA anatomy and function has been performed predominantly by echocardiographic volumetric and Doppler analyses as well as other modalities. Speckle-tracking echocardiography has been well validated as a quantitative assessment tool for LV function, and more recently this technique has been described for assessment of regional and global LA function. Atrial strain has now been evaluated in multiple conditions, including hypertension, diabetes, heart failure, ischemic and valvular heart disease, and atrial fibrillation, including the facilitation of stroke risk calculation and assessment of prognostic implications.


The widespread clinical adoption of this approach will require the definition of normal reference ranges; to date, two review articles have recommended reference ranges on the basis of three studies. However, reported normal ranges of LA strain components have some degree of methodologic variations, for example, timing of initial onset (onset of the P wave or the QRS complex), inclusion or exclusion of the roof of the left atrium, and which apical views were used (four-chamber view only or four- and two-chamber views or all three views), resulting in a wide range of normal values of LA reservoir strain, from 27.6% to 59.8%.


Speckle-tracking values for mean LV strain and right ventricular strain (in children) have displayed a high level of heterogeneity ( I 2 = 99% and I 2 = 94.6%, respectively), and meta-analyses for both have resulted in a demonstration of normal values and encouraged further research. Given the variability of reported normal atrial strain values, the more recent publication of LA strain values in larger patient cohorts has presented an opportunity to establish a consensus by meta-analysis of a large number of healthy control subjects to establish a normal reference range. Thus, the aims of this study were (1) to demonstrate normal ranges of LA strain components via systematic review of the literature and meta-analysis, (2) to identify sources of variation affecting these strains by meta-regression, and (3) to explore methodologic differences via subgroup analysis.


Methods


Search Profile


We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines when performing our systematic review and meta-analysis. Under the guidance of a librarian trained in systematic review, we searched the PubMed, Embase, and Scopus databases for the key terms “left atrial/atrial/atrium” and “strain/function/deformation/stiffness” and “speckle-tracking/Velocity Vector Imaging/edge tracking.” Additional strategies involved reference searches to identify further relevant studies. The search was limited to adult human studies published in English. Abstracts without complete published articles, review articles, editorials, and letters were excluded on secondary review. The search was completed on July 25, 2016. The study was prospectively registered with the Prospero database on September 1, 2015 (CRD42015026143).


Study Selection


Studies were included if articles included LA strain as measured by two-dimensional speckle-tracking, including Velocity Vector Imaging and edge tracking among healthy control subjects. We excluded studies of control subjects with cardiovascular risk factors and studies that did not provide adequate descriptions of baseline characteristics of their control populations, thereby making assessment of the normality or health of participants impossible. We also excluded studies in which LA strain was calculated using Doppler tissue imaging, as this technique is angle dependent and has been made obsolete as a result of the more robust speckle-tracking techniques. Studies were assessed for internal consistencies and whether their reported echocardiographic parameters were consistent with known normal reference ranges. Abstract posters were excluded because of inadequate baseline characteristics or methodology. Finally, we excluded studies with sample sizes < 30 healthy or normal control subjects.


Data Collection


Two investigators (F.P. and N.D.) collected study characteristics, clinical characteristics, and echocardiographic and strain data from individual studies. Disagreements were resolved by consensus or in combination with a third investigator (K.N.).


Strain values corresponding to reservoir, conduit, and contractile function were recorded. Two protocols for LA strain measurement have been described, depending on the use of the P wave (P-P gating) or the QRS complex (R-R gating) as the initiation of the strain calculation ( Figure 1 ). When the R wave is used, all strain values are positive, and there are two peaks that correspond to reservoir function (first peak between R wave and T wave) and atrial contractile function (starting on the P wave); the difference between reservoir strain and atrial contractile strain values reflects conduit function.




Figure 1


Two types of zero reference points.


When the P wave is used, the cycle is defined by an asymmetric sinusoidal curve, an initial negative deflection that represents atrial contractile function and a positive peak that represents conduit function; the sum of these equals reservoir strain. With these methods, LA reservoir strain (εR), conduit strain (εCD), and contractile strain (εCT) should be interchangeable when viewed as scalar quantities. Because the nomenclature for these values is predicated on the type of gating, the zero reference point (R-R or P-P) was recorded, inferred from the images available or in one case established by correspondence with the author. In situations in which multiple articles were published using the same data set, the largest study was included in our analysis.


Statistical Analysis


The means and 95% CIs for reservoir, conduit, and contractile function were computed using a random-effects model. Heterogeneity among studies was assessed using Cochrane’s Q test, with a significant P value of <.10, and the I 2 statistic. Because a number of variables affect atrial strain values, we performed a meta–regression analysis to assess their influence on the normal strain values. Univariate regression was performed if ≥10 studies reported the corresponding variable. Subgroup analysis was performed to evaluate the effect of distinct groups on strain values. A sensitivity analysis was performed by comparing the random-effects model with a fixed-effects model and by removing non-GE studies and demonstrating stability of the estimates.


Publication bias was assessed using a funnel plot and the Egger test, with a P value < .10 considered to indicate statistical significance. Statistical analysis was performed using Comprehensive Meta-Analysis version 2.2.064 (Biostat, Englewood, NJ) and R version 3.2.2 (The R Foundation for Statistical Computing, Vienna, Austria), with two-tailed P values < .05 considered to indicate statistical significance.


Quality of the studies was assessed using the quality assessment tool of Downs and Black, which covers the quality of reporting and external and internal validity. As implemented in a recent meta-analysis of right ventricular strain, we identified documentation of inter- and intraobserver variability, documentation of blood pressure and heart rate, blinding of those acquiring and generating data, and a defined strain computation protocol as important quality metrics.




Results


Study Selection


Figure 2 shows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of our study. Our initial search strategy revealed 2,321 results, with 20 additional articles identified through other sources. After removing duplicates (865 studies), studies were excluded following review of titles (659 studies) and abstracts (726 studies) for the following reasons: no two-dimensional global atrial strain data; no normal or healthy patients or control subjects with cardiovascular risk factors; sample size < 30; abstracts presented at meetings or conferences with incomplete patient or test characteristics without corresponding articles; and miscellaneous exclusions, including editorials, letters, and review articles. Ninety-one full-text studies were assessed for eligibility. An additional 51 studies were excluded for reasons such as those cited above and studies with repeat data sets ( Supplemental Table S1 ). Finally, we included 40 valid studies (2,542 patients) providing information on reservoir function for our final analysis. Fourteen studies (805 patients) reported conduit function, and 18 studies (1,005 patients) were suitable for meta-analysis of contractile function ( Figure 2 ).




Figure 2


Study design. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart demonstrating study selection process. Reasons for full-text exclusion are reported in Supplemental Table S1 .


The baseline study characteristics recorded are shown in Table 1 . Most studies ( n = 34) used GE echocardiographic platforms and GE’s proprietary software. Six studies were performed on non-GE platforms. Similarly, all but three studies used R-R gating as the zero reference point. There was considerable variation with respect to age (mean age range, 25–68 years), gender composition (0%–100% female subjects). Baseline clinical (heart rate, body surface area (BSA), body mass index) and echocardiographic characteristics were within the normal ranges, as would be expected in healthy control cohorts. Feasibility of measurement was reported in 10 studies, ranging from 83.3% to 96.7% on a per-patient basis and from 93.8% to 98.1% on a per-segment basis.



Table 1

Study characteristics

































































































































































































































































































































































































































































































































































































































































































































































































































































































Study Year n Trackability (%) Gating Views Model Age (y) Female (%) HR (beats/min) BMI (kg/m 2 ) SBP (mm Hg) LAVI (mL/m 2 ) LVMI (g/m 2 ) LVEF (%) Average E/e′ FR (Hz) Platform Software Strain
Cameli et al. 2009 60 96.9 (83.3 pts) R-R 4,2 12 33 ± 14 48 73 ± 10 23 ± 2 120 ± 11 NR NR 60 ± 4 NR 60–80 Vivid 7 EchoPAC R
Kim et al. 2009 54 94 R-R 4,2 12 44 ± 10 69 76 ± 11 24 ± 3 119 ± 12 24 ± 4 71 ± 17 63 ± 5 NR 40–80 Vivid 7 EchoPAC R, CD, CT
Rosca et al. 2010 37 NR R-R 4 6 48 ± 12 57 NR 25 ± 3 NR 33 ± 8 87 ± 13 62 ± 3 6.3 ± 1.5 60–100 Vivid 7 EchoPAC R
Saraiva et al. 2010 64 93.8 P-P 4,2,3 15 40 ± 14 69 69 ± 10 26 ± 4 118 ± 12 22 ± 5 NR 74 ± 7 6.4 ± 1.6 64 ± 7 Vivid 7 EchoPAC R, CD, CT
Cameli et al. 2011 52 95.9 R-R 4,2 12 64 ± 16 48 77 ± 12 24 ± 2 122 ± 9 25 ± 5 84 ± 26 59 ± 7 NR 60–80 Vivid 7 EchoPAC R, CD
Miyoshi et al. 2011 30 NR R-R 4 6 58 ± 7 NR 70 ± 9 24 ± 3 132 ± 11 25 ± 10 110 ± 21 74 ± 8 NR 60–100 Vivid 7 EchoPAC R, CD, CT
Mondillo et al. 2011 36 95.1 R-R 4,2 12 62 ± 13 53 76 ± 14 24 ± 2 127 ± 11 22 ± 4 82 ± 29 59 ± 7 6.9 ± 4.3 60–80 Vivid 7 EchoPAC R, CD, CT
Kadappu et al. 2012 73 NR R-R 4 6 43 ± 10 NR NR NR 126 + 11 21 ± 5 81 ± 27 61 ± 4 8.1 ± 2.1 70 Vivid 7 EchoPAC R
Yoon et al. 2012 36 NR R-R 4 NR 53 ± 14 39 63 ± 9 NR NR 27 ± 9 86 ± 18 62 ± 4 NR 50–80 Vivid 7 EchoPAC R
Altekin et al. 2013 60 NR R-R 4,2 12 39 ± 10 48 75 ± 10 26 ± 4 119 ± 11 24 ± 6 NR NR 7.3 ± 1.7 60–80 Vivid 7 EchoPAC R, CD, CT
Ancona et al. 2013 70 NR R-R 4,2 12 51 ± 12 84 76 ± 16 NR 114 ± 9 22 ± 6 NR 58 ± 5 NR 50–90 Vivid 7 EchoPAC R
Hong et al. 2013 30 96.8 P-P 4,2 12 49 ± 8 40 64 ± 8 24 ± 3 114 ± 11 28 ± 5 NR 65 ± 6 7.0 ± 2.4 >40 Vivid 7 EchoPAC R, CD, CT
Liu et al. 2013 30 NR R-R 4 6 40 ± 11 30 70 ± 11 NR 102 ± 20 24 ± 5 NR 63 ± 4 NR 57–72 Vivid 7 EchoPAC R
Mochizuki et al. 2013 77 99 R-R 4,2 12 32 ± 14 38 68 ± 12 22 ± 3 113 ± 10 23 ± 7 69 ± 18 69 ± 5 NR >40 Artida Artida R
Oishi et al. 2013 56 NR R-R 4 6 66 ± 14 NR NR 21 ± 3 124 ± 14 28 ± 9 101 ± 26 73 ± 7 8.7 ± 2.4 60–100 Vivid 7 EchoPAC R, CD, CT
Sun et al. 2013 121 98.1 (96.7 pts) R-R 4,2,3 12 45 ± 17 46 72 ± 10 NR 118 ± 13 32 ± 8 (NI) NR 63 ± 6 NR 60–90 Vivid 7 EchoPAC R, CT
Deschle et al. 2014 32 NR R-R 4,2 12 44 ± 5 38 NR NR NR NR 84 ± 18 NR 9 ± 2 >40 Vivid 7 EchoPAC R
Degirmenci et al. 2014 80 NR R-R 4,2 15 55 ± 8 17 NR NR 121 ± 3 41 ± 10 (NI) NR 60 ± 5 NR 60–90 Vivid 7 EchoPAC R
Santos et al. 2014 40 NR R-R 4,2 12 68 ± 6 68 71 ± 14 25 ± 4 127 ± 15 21 ± 5 78 ± 17 60 ± 3 NR 50–80 NR TomTec R
Tadic et al. 2014 64 NR R-R 4,2 12 46 ± 9 42 70 ± 7 24 ± 3 118 ± 6 29 ± 6 38 ± 5 65 ± 5 5.7 ± 1.9 NR Vivid 7 EchoPAC R
Tadic et al. 2014 38 NR R-R 4,2 12 41 ± 8 100 72 ± 9 25 ± 5 120 ± 9 26 ± 5 38.8 64 ± 4 5.0 ± 1.4 NR Vivid 7 EchoPAC R
Tigen et al. 2014 40 NR R-R 4 6 47 ± 11 45 NR NR NR 39 ± 12 89 ± 20 71 ± 6 NR >40 Vivid 7 EchoPAC R
Yang et al. 2014 152 NR R-R 4 6 48 ± 8 46 NR 23 ± 3 115 ± 11 NR 70 ± 17 65 ± 5 NR 60–80 Vivid E9 EchoPAC R
D’Ascenzi et al. 2015 90 NR R-R 4,2 12 25 ± 4 39 72 ± 17 NR 120 ± 8 18 ± 8 71 ± 15 62 ± 4 6.1 ± 1.4 NR Vivid 7 EchoPAC R, CT
Kocabay et al. 2015 30 97 R-R 4 6 35 ± 6 0 NR 26 ± 3 119 ± 8 20 ± 2 68 ± 12 63 ± 5 6.1 ± 1.5 60–90 Vivid 7 EchoPAC R, CT
Miyoshi et al. 2015 50 NR R-R 4 6 60 ± 10 NR 63 ± 12 21 ± 2 115 ± 11 23 ± 4 75 ± 17 73 ± 7 8.2 ± 1.9 60–100 Vivid 7 EchoPAC R, CD, CT
Montserrat et al. 2015 33 NR R-R 4 6 50 ± 12 21 NR 25 ± 3 NR 23 ± 7 NR 62 ± 4 NR >50 iE33 QLAB R
Morris et al. 2015 329 95.1 pts R-R 4,2 12 36 ± 13 47 NR 22 ± 3 119 ± 10 18 ± 6 75 ± 15 64 ± 6 NR NR Vivid 7/E9 EchoPAC R
Song et al. 2015 50 NR R-R 4 6 28 ± 3 100 76 ± 5 NR 117 ± 7 19 ± 3 NR 66 ± 4 NR 60–91 Vivid 7 EchoPAC R, CD
Xu et al. 2015 124 NR R-R 4,2,3 18 51 ± 12 39 70 ± 10 22 ± 2 119 ± 9 33 ± 8 94 ± 20 63 ± 5 NR 60–90 Vivid 9 EchoPAC R
Badran et al. 2015 33 NR R-R 4 6 43 ± 12 46 72 ± 15 NR 117 ± 10 12 ± 5 112 ± 31 62 ± 6 NR 57–72 Esaote MyLab Gold 30 Xstrain (Esaote) R
Liu et al. 2015 39 NR R-R 4 6 46 ± 18 38 75 ± 11 NR 119 ± 15 24 ± 5 NR 63 ± 5 NR 40–81 Vivid 7 EchoPAC R
Atas et al. 2016 38 NR R-R 4 6 49 ± 11 92 NR 25.3 ± 5.7 NR NR 84 ± 17 69 ± 6 6.2 ± 1.4 >40 iE33 QLAB R, CT
Guo et al. 2016 50 NR R-R 4,2 12 50 ± 7 46 NR 26 ± 2 128 ± 6 26 ± 5 NR 65 ± 5 7.4 ± 1.6 40–80 Vivid E9 EchoPAC R, CD, CT
Kadappu et al. 2016 76 NR R-R 4,2 12 62 ± 7 66 NR 26 ± 5 123 ± 12 22.3 ± 4.5 85 ± 28 60 ± 5 8.9 ± 2.5 >70 Vivid E9 EchoPAC R
Karakoyun et al. 2016 30 NR R-R 4 6 32 ± 7 47 73 ± 12 27 ± 5 118 ± 11 NR NR 62 ± 3 NR 50–90 Vivid 7 EchoPAC R, CT
Kim et al. 2016 79 NR R-R 4 NR 54 ± 11 24 65 ± 11 NR NR 30 ± 9 NR NR 8.6 ± 2.7 50–80 Vivid 7 EchoPAC R
Tadic et al. 2016 45 NR P-P 4,2 12 43 ± 12 100 70 ± 7 23 ± 4 122 ± 8 23.5 ± 7 NR 65 ± 3 5.7 ± 1.3 NR Vivid 7 EchoPAC R, CD, CT
Mochizuki et al. 2016 69 NR R-R 4,2 12 52 ± 16 62 65 ± 10 21 ± 3 120 ± 15 26 ± 8 72 ± 17 66 ± 5 NR 60–80 Vivid E9 EchoPAC R
Wang et al. 2016 45 NR R-R 4,2 NR 49 ± 8 51 72 ± 10 23 ± 3 116 ± 12 26 ± 6 NR 62 ± 5 NR >60 ProSound F75 Hitachi DAS-RS1 R, CD, CT

BMI , Body mass index; FR , frame rate; HR , heart rate; LAVI , LA volume index; LVEF , LV ejection fraction; LVMI , LV mass index; NR , not reported; pt , patient; SBP , systolic blood pressure.

Trackability reported as percentage of segments tracked or percentage of patients with appropriate images.


Aorta and atrioventricular curtain excluded in three-chamber view.


Roof excluded in four-, two-, and three-chamber views.



Normal Strain Values


The pooled normal values for εR, εCD, and εCT were 39.4% (95% CI, 38.0%–40.8%), 23.0% (95% CI, 20.7%–25.2%), and 17.4% (95% CI, 16.0%–19.0%), respectively ( Table 2 ).



Table 2

Summary of normal ranges of LA strain components




































LA strain component Number of studies Mean 95% CI Cochrane Q I 2 τ 2
Reservoir 40 39.4 38.0–40.8 1,653 ( P < .001) 97.6 20.0
Conduit 14 23.0 20.7–25.2 420 ( P < .001) 96.9 17.9
Contractile 18 17.4 16.0–19.0 631 ( P < .001) 97.3 9.7


Reservoir Function


All 40 studies reported reservoir strain. Normal reservoir strain ranged from 27.6% to 59.8%. The mean εR was 39.4% (95% CI, 38.0%–40.8%) ( Figure 3 A). There was significant heterogeneity ( Q = 1,653, P < .0001, I 2 = 97.6%) ( Table 2 ).








Figure 3


Normal ranges of LA strain components: (A) εR, (B) εCD, and (C) εCT.


Sensitivity Analysis


We performed analysis using a fixed-effects model and demonstrated a mean εR of 38.4% (95% CI, 38.2%–38.6%). Removing six non-GE studies, we demonstrated that the mean strain value for GE-based systems was 39.3% (95% CI, 37.5%–41.1%) on the basis of a random-effects model. The forest plot for GE-only studies is provided in Supplemental Figure S1 .


Conduit Function


Normal conduit strain ranged from 15.7% to 33.4%, with a mean εCD of 23.0% (95% CI, 20.7%–25.2%). This was also heterogeneous ( Q = 420, P < .001, I 2 = 96.9%) ( Figure 3 B). Only one study was performed on a non-GE platform.


Contractile Function


Reports of normal atrial contractile strain also varied, with values ranging from 14.0% to 25.0%. The mean εCT was 17.4% (95% CI, 16.0%–19.0%). The heterogeneity was evidenced by a Q statistic of 631 ( P < .001) and an I 2 value of 97.3%.


Meta-Regression


The sources of heterogeneity were examined by meta-regression ( Table 3 ). Heart rate (β = 0.48, P = .02) and BSA (β = −25.2, P = .003) were significantly associated with εR.



Table 3

Meta–regression analysis for εR










































































εR Number of studies β (95% CI) P
Age, per 1 y 40 −0.10 (−0.26 to 0.06) .21
SBP, per 1 mm Hg 33 −0.03 (−0.35 to 0.28) .85
LVEF, per 1% 38 0.09 (−0.26 to 0.43) .62
E/e′, per 1unit 18 −1.74 (−4.53 to 1.04) .22
LA volume, per 1 mL/m 2 32 0.01 (−0.35 to 0.36) .96
LV mass, per 1 g/m 2 22 −0.01 (−0.15 to 0.13) .87
Publication year, per 1 y 40 0.40 (−0.31 to 1.13) .26
Sample size, per one patient 40 0.02 (−0.01 to 0.05) .22
% female, per 1% 36 0.04 (−0.04 to 0.11) .32
Heart rate, per 1 beat/min 27 0.48 (0.10 to 0.87) .02
BMI, per 1 kg/m 2 27 0.74 (−0.31 to 1.79) .16
BSA, per 1 m 2 24 −25.2 (−43.6 to −8.7) .003
EchoPAC version 14 0.49 (−0.53 to 1.52) .35

BMI , Body mass index; LVEF , LV ejection fraction; SBP , systolic blood pressure.

Boldface P values are < 0.05.


Corresponding regression analysis for εCD and εCT is provided in the Supplemental Appendix .


Meta-regression analysis for conduit function revealed that increasing body mass index was associated with increasing εCD (β = 1.5, P = .02) ( Supplemental Table S2 ). For contractile function, meta–regression analysis revealed that LA volume index (β = 0.46, P = .02) and BSA (β = −16.9, P = .04) had a significant influence on εCT, with sample size trending toward significance ( P = .06) ( Supplemental Table S3 ).


Subgroup Analysis


The results of subgroup analyses are summarized in Figure 4 . With regard to the different zero reference points, 37 studies used R-R gating and three used P-P gating. Reservoir function was 40% (95% CI, 38%–41%) when R-R gating was used and 37% (95% CI, 34%–41%) when P-P gating was used ( P = .24).




Figure 4


Subgroup analysis of εR.


Vendor difference was also examined, but there was no significant difference between GE ( n = 34) and non-GE ( n = 6) systems: 39% (95% CI, 38%–41%) versus 40% (95% CI, 35%–45%) ( P = .76).


Methodologic differences in the model used to evaluate strain were assessed by comparing studies that incorporated one, two, or three apical views (i.e., four-chamber view only; four- and two-chamber views; and four-, two-, and three-chamber views). The mean εR values for studies using four-chamber view only (17 studies), four- and two-chamber views (19 studies), and four-, two-, and three-chamber views (four studies) were 38% (95% CI, 35%–41%), 41% (95% CI, 39%–43%), and 39% (95% CI, 31%–47%), respectively ( P = .33).


Because only one study specifically stipulated the racial distribution of the population, we compared studies performed in Asian countries ( n = 17) with those performed in non-Asian countries ( n = 22) to examine the possibility of a racial influence. One multicenter study performed in Germany and Asia was excluded from this analysis. There was no significant difference in the mean εR values between studies performed in Asia, 38% (95% CI, 35%–41%), and those outside of Asia, 40% (95% CI, 38%–42%) ( P = .21).


We also compared the mean εR between large ( n ≥ 100, four studies) and small ( n < 100, 36 studies) studies, demonstrating that large studies yielded larger values of εR than small studies (44% [95% CI, 40%–48%] vs 38% [95% CI, 37%–40%], P = .02).


Publication Bias


Publication bias was explored using a funnel plot for all studies and those reporting conduit and contractile function. There was no significant publication bias for reservoir, conduit, or contractile function, as evidenced by the respective Egger test P values of .39, .41, and .56. These and the funnel plots are included in Supplemental Figure S2 . The Egger test P value for εR using GE-only studies was .06, suggesting significant publication bias.


Quality of Studies


All studies defined study objective, described the outcomes, and outlined the main findings. As specified, descriptions of heart rate and blood pressure were essential in the characterization of control subjects, and these data points were absent from 15 studies. All studies described echocardiographic confounders with variations consistent with echocardiographic parameters reported. All but one study defined the strain computation protocol. Thirteen studies specifically stipulated blinding individuals generating outcome data, and four studies blinded sonographers to patient characteristics. Last, reproducibility analysis was performed in 28 studies. The summary of quality analysis can be seen in Supplemental Table S4 .




Results


Study Selection


Figure 2 shows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of our study. Our initial search strategy revealed 2,321 results, with 20 additional articles identified through other sources. After removing duplicates (865 studies), studies were excluded following review of titles (659 studies) and abstracts (726 studies) for the following reasons: no two-dimensional global atrial strain data; no normal or healthy patients or control subjects with cardiovascular risk factors; sample size < 30; abstracts presented at meetings or conferences with incomplete patient or test characteristics without corresponding articles; and miscellaneous exclusions, including editorials, letters, and review articles. Ninety-one full-text studies were assessed for eligibility. An additional 51 studies were excluded for reasons such as those cited above and studies with repeat data sets ( Supplemental Table S1 ). Finally, we included 40 valid studies (2,542 patients) providing information on reservoir function for our final analysis. Fourteen studies (805 patients) reported conduit function, and 18 studies (1,005 patients) were suitable for meta-analysis of contractile function ( Figure 2 ).




Figure 2


Study design. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart demonstrating study selection process. Reasons for full-text exclusion are reported in Supplemental Table S1 .


The baseline study characteristics recorded are shown in Table 1 . Most studies ( n = 34) used GE echocardiographic platforms and GE’s proprietary software. Six studies were performed on non-GE platforms. Similarly, all but three studies used R-R gating as the zero reference point. There was considerable variation with respect to age (mean age range, 25–68 years), gender composition (0%–100% female subjects). Baseline clinical (heart rate, body surface area (BSA), body mass index) and echocardiographic characteristics were within the normal ranges, as would be expected in healthy control cohorts. Feasibility of measurement was reported in 10 studies, ranging from 83.3% to 96.7% on a per-patient basis and from 93.8% to 98.1% on a per-segment basis.



Table 1

Study characteristics

































































































































































































































































































































































































































































































































































































































































































































































































































































































Study Year n Trackability (%) Gating Views Model Age (y) Female (%) HR (beats/min) BMI (kg/m 2 ) SBP (mm Hg) LAVI (mL/m 2 ) LVMI (g/m 2 ) LVEF (%) Average E/e′ FR (Hz) Platform Software Strain
Cameli et al. 2009 60 96.9 (83.3 pts) R-R 4,2 12 33 ± 14 48 73 ± 10 23 ± 2 120 ± 11 NR NR 60 ± 4 NR 60–80 Vivid 7 EchoPAC R
Kim et al. 2009 54 94 R-R 4,2 12 44 ± 10 69 76 ± 11 24 ± 3 119 ± 12 24 ± 4 71 ± 17 63 ± 5 NR 40–80 Vivid 7 EchoPAC R, CD, CT
Rosca et al. 2010 37 NR R-R 4 6 48 ± 12 57 NR 25 ± 3 NR 33 ± 8 87 ± 13 62 ± 3 6.3 ± 1.5 60–100 Vivid 7 EchoPAC R
Saraiva et al. 2010 64 93.8 P-P 4,2,3 15 40 ± 14 69 69 ± 10 26 ± 4 118 ± 12 22 ± 5 NR 74 ± 7 6.4 ± 1.6 64 ± 7 Vivid 7 EchoPAC R, CD, CT
Cameli et al. 2011 52 95.9 R-R 4,2 12 64 ± 16 48 77 ± 12 24 ± 2 122 ± 9 25 ± 5 84 ± 26 59 ± 7 NR 60–80 Vivid 7 EchoPAC R, CD
Miyoshi et al. 2011 30 NR R-R 4 6 58 ± 7 NR 70 ± 9 24 ± 3 132 ± 11 25 ± 10 110 ± 21 74 ± 8 NR 60–100 Vivid 7 EchoPAC R, CD, CT
Mondillo et al. 2011 36 95.1 R-R 4,2 12 62 ± 13 53 76 ± 14 24 ± 2 127 ± 11 22 ± 4 82 ± 29 59 ± 7 6.9 ± 4.3 60–80 Vivid 7 EchoPAC R, CD, CT
Kadappu et al. 2012 73 NR R-R 4 6 43 ± 10 NR NR NR 126 + 11 21 ± 5 81 ± 27 61 ± 4 8.1 ± 2.1 70 Vivid 7 EchoPAC R
Yoon et al. 2012 36 NR R-R 4 NR 53 ± 14 39 63 ± 9 NR NR 27 ± 9 86 ± 18 62 ± 4 NR 50–80 Vivid 7 EchoPAC R
Altekin et al. 2013 60 NR R-R 4,2 12 39 ± 10 48 75 ± 10 26 ± 4 119 ± 11 24 ± 6 NR NR 7.3 ± 1.7 60–80 Vivid 7 EchoPAC R, CD, CT
Ancona et al. 2013 70 NR R-R 4,2 12 51 ± 12 84 76 ± 16 NR 114 ± 9 22 ± 6 NR 58 ± 5 NR 50–90 Vivid 7 EchoPAC R
Hong et al. 2013 30 96.8 P-P 4,2 12 49 ± 8 40 64 ± 8 24 ± 3 114 ± 11 28 ± 5 NR 65 ± 6 7.0 ± 2.4 >40 Vivid 7 EchoPAC R, CD, CT
Liu et al. 2013 30 NR R-R 4 6 40 ± 11 30 70 ± 11 NR 102 ± 20 24 ± 5 NR 63 ± 4 NR 57–72 Vivid 7 EchoPAC R
Mochizuki et al. 2013 77 99 R-R 4,2 12 32 ± 14 38 68 ± 12 22 ± 3 113 ± 10 23 ± 7 69 ± 18 69 ± 5 NR >40 Artida Artida R
Oishi et al. 2013 56 NR R-R 4 6 66 ± 14 NR NR 21 ± 3 124 ± 14 28 ± 9 101 ± 26 73 ± 7 8.7 ± 2.4 60–100 Vivid 7 EchoPAC R, CD, CT
Sun et al. 2013 121 98.1 (96.7 pts) R-R 4,2,3 12 45 ± 17 46 72 ± 10 NR 118 ± 13 32 ± 8 (NI) NR 63 ± 6 NR 60–90 Vivid 7 EchoPAC R, CT
Deschle et al. 2014 32 NR R-R 4,2 12 44 ± 5 38 NR NR NR NR 84 ± 18 NR 9 ± 2 >40 Vivid 7 EchoPAC R
Degirmenci et al. 2014 80 NR R-R 4,2 15 55 ± 8 17 NR NR 121 ± 3 41 ± 10 (NI) NR 60 ± 5 NR 60–90 Vivid 7 EchoPAC R
Santos et al. 2014 40 NR R-R 4,2 12 68 ± 6 68 71 ± 14 25 ± 4 127 ± 15 21 ± 5 78 ± 17 60 ± 3 NR 50–80 NR TomTec R
Tadic et al. 2014 64 NR R-R 4,2 12 46 ± 9 42 70 ± 7 24 ± 3 118 ± 6 29 ± 6 38 ± 5 65 ± 5 5.7 ± 1.9 NR Vivid 7 EchoPAC R
Tadic et al. 2014 38 NR R-R 4,2 12 41 ± 8 100 72 ± 9 25 ± 5 120 ± 9 26 ± 5 38.8 64 ± 4 5.0 ± 1.4 NR Vivid 7 EchoPAC R
Tigen et al. 2014 40 NR R-R 4 6 47 ± 11 45 NR NR NR 39 ± 12 89 ± 20 71 ± 6 NR >40 Vivid 7 EchoPAC R
Yang et al. 2014 152 NR R-R 4 6 48 ± 8 46 NR 23 ± 3 115 ± 11 NR 70 ± 17 65 ± 5 NR 60–80 Vivid E9 EchoPAC R
D’Ascenzi et al. 2015 90 NR R-R 4,2 12 25 ± 4 39 72 ± 17 NR 120 ± 8 18 ± 8 71 ± 15 62 ± 4 6.1 ± 1.4 NR Vivid 7 EchoPAC R, CT
Kocabay et al. 2015 30 97 R-R 4 6 35 ± 6 0 NR 26 ± 3 119 ± 8 20 ± 2 68 ± 12 63 ± 5 6.1 ± 1.5 60–90 Vivid 7 EchoPAC R, CT
Miyoshi et al. 2015 50 NR R-R 4 6 60 ± 10 NR 63 ± 12 21 ± 2 115 ± 11 23 ± 4 75 ± 17 73 ± 7 8.2 ± 1.9 60–100 Vivid 7 EchoPAC R, CD, CT
Montserrat et al. 2015 33 NR R-R 4 6 50 ± 12 21 NR 25 ± 3 NR 23 ± 7 NR 62 ± 4 NR >50 iE33 QLAB R
Morris et al. 2015 329 95.1 pts R-R 4,2 12 36 ± 13 47 NR 22 ± 3 119 ± 10 18 ± 6 75 ± 15 64 ± 6 NR NR Vivid 7/E9 EchoPAC R
Song et al. 2015 50 NR R-R 4 6 28 ± 3 100 76 ± 5 NR 117 ± 7 19 ± 3 NR 66 ± 4 NR 60–91 Vivid 7 EchoPAC R, CD
Xu et al. 2015 124 NR R-R 4,2,3 18 51 ± 12 39 70 ± 10 22 ± 2 119 ± 9 33 ± 8 94 ± 20 63 ± 5 NR 60–90 Vivid 9 EchoPAC R
Badran et al. 2015 33 NR R-R 4 6 43 ± 12 46 72 ± 15 NR 117 ± 10 12 ± 5 112 ± 31 62 ± 6 NR 57–72 Esaote MyLab Gold 30 Xstrain (Esaote) R
Liu et al. 2015 39 NR R-R 4 6 46 ± 18 38 75 ± 11 NR 119 ± 15 24 ± 5 NR 63 ± 5 NR 40–81 Vivid 7 EchoPAC R
Atas et al. 2016 38 NR R-R 4 6 49 ± 11 92 NR 25.3 ± 5.7 NR NR 84 ± 17 69 ± 6 6.2 ± 1.4 >40 iE33 QLAB R, CT
Guo et al. 2016 50 NR R-R 4,2 12 50 ± 7 46 NR 26 ± 2 128 ± 6 26 ± 5 NR 65 ± 5 7.4 ± 1.6 40–80 Vivid E9 EchoPAC R, CD, CT
Kadappu et al. 2016 76 NR R-R 4,2 12 62 ± 7 66 NR 26 ± 5 123 ± 12 22.3 ± 4.5 85 ± 28 60 ± 5 8.9 ± 2.5 >70 Vivid E9 EchoPAC R
Karakoyun et al. 2016 30 NR R-R 4 6 32 ± 7 47 73 ± 12 27 ± 5 118 ± 11 NR NR 62 ± 3 NR 50–90 Vivid 7 EchoPAC R, CT
Kim et al. 2016 79 NR R-R 4 NR 54 ± 11 24 65 ± 11 NR NR 30 ± 9 NR NR 8.6 ± 2.7 50–80 Vivid 7 EchoPAC R
Tadic et al. 2016 45 NR P-P 4,2 12 43 ± 12 100 70 ± 7 23 ± 4 122 ± 8 23.5 ± 7 NR 65 ± 3 5.7 ± 1.3 NR Vivid 7 EchoPAC R, CD, CT
Mochizuki et al. 2016 69 NR R-R 4,2 12 52 ± 16 62 65 ± 10 21 ± 3 120 ± 15 26 ± 8 72 ± 17 66 ± 5 NR 60–80 Vivid E9 EchoPAC R
Wang et al. 2016 45 NR R-R 4,2 NR 49 ± 8 51 72 ± 10 23 ± 3 116 ± 12 26 ± 6 NR 62 ± 5 NR >60 ProSound F75 Hitachi DAS-RS1 R, CD, CT

Only gold members can continue reading. Log In or Register to continue

Apr 15, 2018 | Posted by in CARDIOLOGY | Comments Off on Normal Ranges of Left Atrial Strain by Speckle-Tracking Echocardiography: A Systematic Review and Meta-Analysis
Premium Wordpress Themes by UFO Themes