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.

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.

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 ).

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.

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 ).

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 ).

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.

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).

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 .

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 ).

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

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

1. Left Atrial Dysfunction in the Pathogenesis of Cryptogenic Stroke: Novel Insights from Speckle-Tracking Echocardiography
2. Three-dimensional Echocardiography in Congenital Heart Disease: An Expert Consensus Document from the European Association of Cardiovascular Imaging and the American Society of Echocardiography
3. Building A Perioperative Echocardiography Team: Critical and Necessary
4. PQRS Meets MACRA: Help is On the Way!!

Stay updated, free articles. Join our Telegram channel

Join