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Estimation of Left Ventricular Filling Pressure Using Left Atrial Strain in Coarctation of Aorta
Abstract
Background. Left atrial (LA) reservoir strain <18% and booster strain <8% have been proposed as the optimal threshold to detect increased left ventricular (LV) filling pressure in patients with acquired heart disease. The purpose of this study was to determine whether these LA strain cut-off points can detect increased LV filling pressure in adults with coarctation of aorta (COA). Methods. This retrospective study included adults with COA (n = 126; age, 36 ± 16 years) who underwent non-simultaneous cardiac catheterization and echocardiography. Increased LV filling pressure was defined as pulmonary artery wedge pressure (PAWP) >12 mm Hg or LV end-diastolic pressure (LVEDP) >16 mm Hg. Results. The median PAWP was 13 mm Hg (interquartile range [IQR], 11-18) and PAWP had a good correlation with LA reservoir strain (r = -0.69; P<.001) and LA booster strain (r = -0.61; P<.001). LA reservoir strain <18% had superior diagnostic power to detect PAWP >12 mm Hg as compared with LA volume index >34 mL/m2, septal E/e' >15, lateral E/e' >13, and tricuspid regurgitation velocity >2.8 m/s (P<.05 for all). The median LVEDP was 17 mm Hg (IQR, 14-20) and LVEDP had a modest correlation with LA reservoir strain (r = -0.39; P<.001) and LA booster strain (r = -0.33; P<.01). LA reservoir strain <18% had superior diagnostic power to detect LVEDP >16 mm Hg as compared with LA volume index >34 mL/m2, septal E/e' >15, lateral E/e' >13, and tricuspid regurgitation velocity >2.8 m/s (P<.05 for all). Conclusions. These data suggest that LA strain could potentially be used to identify patients with increased LV filling pressure, thereby improving patient selection for cardiac catheterization and interventions.
J INVASIVE CARDIOL 2022;34(12):E858-E865. Epub 2022 November 4.
Key words: echocardiography, left atrium dysfunction, left ventricular diastolic dysfunction
Left ventricular (LV) diastolic dysfunction is common in adults with coarctation of aorta (COA) because of chronic LV pressure overload resulting from mechanical obstruction at the aortic isthmus, vascular and endothelial dysfunction, and LV outflow tract obstruction in the setting of associated left-sided lesions.1-7 Chronic LV pressure overload subsequently leads to cardiac myocyte hypertrophy, mismatch between myocardial oxygen demand and supply, apoptosis with replacement fibrosis, and impaired LV relaxation.8 Over time, these pathologic changes result in alteration in the viscoelastic properties and effective operative compliance of the LV, which in turn leads to increased LV filling pressure.8 Elevated LV filling pressure subsequently leads to left atrial (LA) remodeling, atrial fibrillation, heart failure, and cardiovascular death.8,9 Changes in LV filling pressure are, therefore, a critical link between LV adaptation to abnormal loading conditions and clinical outcomes, and hence the assessment of LV filling pressure is important for prognostication and optimization of therapy.
Although cardiac catheterization is the gold standard for the assessment of LV filling pressure, it is invasive and hence, not ideal for routine assessment and serial monitoring in ambulatory patients. Echocardiography provided a non-invasive alternative method for the estimation of LV filling pressure based on a multiparametric algorithm endorsed by the American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI).10 This approach has some limitations because the different echocardiographic indices may not be available in each patient or the values of the different indices may be discordant, leading to a diagnosis of indeterminate LV filling pressure.10
LA strain imaging provides a robust assessment of LA function, and emerging data suggest that LA strain imaging also provides an assessment of LV diastolic function and estimation of LV filling pressure.11-14 In a recent study, Inoue et al15 demonstrated that LA reservoir strain <18% and LA booster strain <8% had superior diagnostic power to identify patients with elevated LV filling pressure as compared with conventional echocardiographic indices of LV diastolic function. However, patients with congenital heart disease were excluded from the study, and hence the diagnostic role of LA strain imaging for estimating LV filling pressure is unknown in this population, including patients with COA known to have a high prevalence of LV diastolic dysfunction. The purpose of this study was to assess the correlation between LA strain and LV filling pressure in adults with COA and to determine whether the proposed LA strain cut-off points (LA reservoir strain <18% and LA booster strain <8%) can detect increased LV filling pressure in this population.
Methods
Study population. This is a retrospective study of adults (age >18 years) with COA who underwent right heart catheterization (RHC) and/or left heart catheterization (LHC) from January 1, 2003 and December 31, 2019. From this cohort, we selected consecutive patients with adequate echocardiographic images (obtained within 7 days prior to the time of cardiac catheterization) for offline assessment of LA strain. We excluded patients with concomitant LV inflow disease, defined as supravalvular/valvular/subvalvular mitral stenosis with mean gradient greater than or equal to 3 mm Hg, greater than or equal to moderate mitral regurgitation, or the presence of a mitral valve prosthesis. Figure 1 shows the flow chart for cohort selection.
Study objectives. The study objectives were: (1) to assess the correlation between LA reservoir strain and pulmonary artery wedge pressure (PAWP), and compare the diagnostic power of LA strain (LA reservoir strain <18% and LA booster strain <8%) to detect increased LV filling pressure, defined as PAWP >12 mm Hg, with that of conventional echocardiographic indices of LV diastolic function;15-17 and (2) to assess the correlation between LA reservoir strain and left ventricular end-diastolic pressure (LVEDP), and compare the diagnostic power of LA strain (LA reservoir strain <18% and LA booster strain <8%) to detect increased LV filling pressure, defined as LVEDP >16 mm Hg, with that of conventional echocardiographic indices of LV diastolic function.15-17 Sensitivity analysis was performed to assess the diagnostic power of LA strain in patients with preserved LV ejection fraction (defined as LV ejection fraction ≥50%) vs patients with reduced LV ejection fraction (defined as LV ejection fraction <50%).
Echocardiographic assessment of LA function. The procedural details for speckle tracking strain imaging in our laboratory have been described.18,19 In brief, LA strain was obtained using Vivid E9 and E95 (General Electric Co) with M5S and M5Sc-D transducers (1.5-4.6 MHz) at a frame rate of 40-80 Hz, and these images were exported (DICOM) and then analyzed offline using TomTec (TomTec Imaging Systems). Adequate tracking by the software was visually verified and retraced if necessary until adequate tracking was achieved. LA reservoir strain, LA conduit strain, and LA booster strain were assessed using the QRS as the fiduciary point, as shown in Figure 2.
Conventional echocardiographic indices of LV diastolic function. We defined increased LV filling pressure using the conventional echocardiographic indices of diastolic function as follows: (1) ratio of septal mitral inflow pulsed wave Doppler early velocity to tissue Doppler early velocity (E/e') >15 or lateral E/e' >13; (2) LA volume index >34 mL/m2; and (3) tricuspid regurgitation velocity >2.8 m/s.
Cardiac catheterization. All studies were performed on chronic medications in a fasting state and under mild sedation. Pressure measurements were recorded as an average of ≥5 cardiac cycles under spontaneous breathing. In patients who underwent RHC, venous access was obtained via right internal jugular vein or right femoral vein using 7-Fr balloon-tipped catheters. PAWP was measured after confirming proper wedge position using oximetry and pressure waveform. In patients who underwent LHC, arterial access was obtained via right radial or right femoral artery and arterial catheterization was performed using a 4-Fr or 5-Fr pigtail catheter. Oxygen saturation was measured using standard technique and cardiac output was calculated using the Fick method.
Statistical analysis. Data were presented as mean ± standard deviation, median (interquartile range [IQR]), or count (%). Normality was assessed using the Shapiro-Wilk test of normality. The relationship between continuous variables was assessed using Pearson’s correlation. The diagnostic power of the different indices to detect high LV filling pressure was assessed using the area under the curve (AUC) derived from logistic regression, and compared using AUC comparison.20 All statistical analyses were performed with BlueSky Statistics software, version 7.40 (BlueSky Statistics LLC) and SAS, version 9.4 (SAS Institute Inc). A P-value <.05 was considered statistically significant for all analyses.
Results
Baseline characteristics. The baseline characteristics of the study cohort are shown in Table 1. Among 126 patients who met the study inclusion criteria, the mean age at the time of cardiac catheterization was 36 ± 16 years and 79 (63%) were males. Of the 126 patients, 14 (11%) underwent RHC alone, 47 (37%) underwent LHC alone, and 65 (52%) underwent both RHC and LHC. The primary indication for cardiac catheterization was for the assessment of COA gradient /transcatheter COA intervention in 51 patients (40%), preoperative assessment in 39 patients (31%), and heart failure evaluation in 36 patients (29%).
Echocardiographic data. The echocardiographic and cardiac catheterization data of the study cohort are shown in Table 2. The median interval between echocardiogram and cardiac catheterization was 2 days (IQR, 1-4) and 74 patients (59%) underwent both echocardiogram and cardiac catheterization within 2 days.
LA reservoir strain was assessed in all patients (inclusion criterion) and the mean LA reservoir strain was 39 ± 12%. The mean LA booster strain was 15 ± 7% and the mean LA conduit strain was 23 ± 9%. Of the 126 patients, 7 (6%) did not have LA booster strain and conduit strain data because of atrial fibrillation at the time of echocardiogram. Of the conventional echocardiographic indices of diastolic function assessed in this study, the mean septal E/e’, lateral E/e’, and average E/e’ were 13.3 ± 6.1, 9.5 ± 5.8, and 11.8 ± 4.2, respectively. The median tricuspid regurgitation velocity and LA volume index were 2.6 m/s (IQR, 2.4-3.1) and 32 mL/m2 (IQR, 24-39), respectively.
Correlation between the LA strain and PAWP. PAWP was measured in 79 patients (63%); median PAWP was 13 mm Hg (IQR, 11-18) and 44 of 79 patients (56%) had a PAWP >12 mm Hg. There was a good correlation between LA reservoir strain and PAWP (r = -0.69; P<.001) and between LA booster strain and PAWP (r = -0.61; P<.001) (Figure 3). Of the 79 patients, 73 were in sinus rhythm while 4 patients were in atrial fibrillation and 2 patients had right ventricular pacing at the time of echocardiogram. There was a good correlation between LA reservoir strain and PAWP (r = -0.71; P<.001) and between LA booster strain and PAWP (r = -0.64; P<.001) among the patients in sinus rhythm. However, we could not assess the correlation between LA strain and PAWP in the patients with atrial fibrillation or right ventricular pacing because of small sample size.
Of the conventional echocardiographic indices of diastolic function assessed, only LA volume index had a correlation with PAWP (r = 0.32; P<.01) (Table 3). LA reservoir strain <18% identified patients with PAWP >12 mm Hg with sensitivity and specificity of 89% and 87%, respectively, while LA booster strain <8% identified patients with PAWP >12 mm Hg with sensitivity and specificity of 86% and 76%, respectively (Table 4). LA reservoir strain <18% had superior diagnostic power to detect PAWP >12 mm Hg as compared with LA booster strain <8% (AUC difference, 0.09; 95% confidence interval [CI], 0.02-0.14; P<.01). Similarly, LA reservoir strain <18% had superior diagnostic power to detect PAWP >12 mm Hg as compared with LA volume index >34 mL/m2 (AUC difference, 0.15; 95% CI, 0.09-0.21; P<.001), septal E/e' >15 (AUC difference, 0.13; 95% CI, 0.08-0.18; P<.01), lateral E/e' >13 (AUC difference, 0.14; 95% CI, 0.07-0.21; P<.01), and tricuspid regurgitation velocity >2.8 m/s (AUC difference, 0.23; 95% CI, 0.15-0.31; P<.001) (Table 4).
We performed a sensitivity analysis to assess the diagnostic power of LA reservoir strain and LA booster strain to detect PAWP >12 mm Hg in patients with preserved LV ejection fraction vs reduced LV ejection fraction. Of the 79 patients, 62 (79%) had preserved LV ejection fraction while 17 (21%) had reduced LV ejection fraction. LA reservoir strain had superior diagnostic power to detect increased PAWP among patients with reduced LV ejection fraction (AUC, 0.88; 95% CI, 0.81-0.95) as compared with patients with preserved LV ejection fraction (AUC, 0.79; 95% CI, 0.73-0.85; AUC difference, 0.09; 95% CI, 0.02-0.16; P<.01). Similarly, LA booster strain has superior diagnostic power to detect increased PAWP among patients with reduced LV ejection fraction (AUC, 0.81; 95% CI, 0.75-0.87) as compared with patients with preserved LV ejection fraction (AUC, 0.72; 95% CI, 0.68-0.76; AUC difference, 0.08; 95% CI, 0.03-0.13; P<.01).
Correlation between the LA strain and LVEDP. LVEDP was measured in 112 patients (89%); the median LVEDP was 17 mm Hg (IQR, 14-20) and 61 of 112 patients (55%) had elevated LVEDP (>16 mm Hg). There was a modest correlation between LA reservoir strain and LVEDP (r = -0.39; P<.001) and between LA booster strain and LVEDP (r = -0.33; P<.01) (Figure 2). Of the 112 patients, 103 were in sinus rhythm while 6 patients were in atrial fibrillation and 3 patients had right ventricular pacing at the time of echocardiogram. We observed a modest correlation between LA reservoir strain and LVEDP (r = -0.43; P<.001) and between LA booster strain and LVEDP (r = -0.36; P<.001) among the patients in sinus rhythm. Similar analyses were not performed in the patients with atrial fibrillation or right ventricular pacing because of small sample size.
Of the conventional echocardiographic indices of diastolic function assessed in this study, only septal E/e’ had a correlation with LVEDP (r = 0.27; P=.01) (Table 5). LA reservoir strain <18% identified patients with LVEDP >16 mm Hg with sensitivity and specificity of 78% and 79%, respectively, while LA booster strain <8% identified patients with LVEDP >16 mm Hg with sensitivity and specificity of 72% and 77%, respectively (Table 6). LA reservoir strain <18% had a superior diagnostic power to detect LVEDP >16 mm Hg as compared with LA booster strain <8% (AUC difference, 0.05; 95% CI, 0.01-0.09; P=.03). Similarly, LA reservoir strain <18% had a superior diagnostic power to detect LVEDP >16 mm Hg as compared with LA volume index >34 mL/m2 (AUC difference, 0.12; 95% CI, 0.08-0.16; P<.001), septal E/e' >15 (AUC difference, 0.08; 95% CI, 0.02-0.12; P=.03), lateral E/e' >13 (AUC difference, 0.09; 95% CI, 0.03-0.15; P=.02), and tricuspid regurgitation >2.8 m/s (AUC difference, 0.19; 95% CI, 0.14-0.24; P<.001) (Table 6).
Of the 112 patients, 91 (81%) had preserved LV ejection fraction while 21 (19%) had reduced LV ejection fraction. LA reservoir strain had superior diagnostic power to detect increased LVEDP among patients with reduced LV ejection fraction (AUC, 0.80; 95% CI, 0.86-0.84) as compared with patients with preserved LV ejection fraction (AUC, 0.73; 95% CI, 0.69-0.77; AUC difference, 0.07; 95% CI, 0.03-0.11; P<.01). Similarly, LA booster strain had superior diagnostic power to detect increased LVEDP among patients with reduced LV ejection fraction (AUC, 0.84; 95% CI, 0.79-0.89) as compared with patients with preserved LV ejection fraction (AUC, 0.78; 95% CI, 0.72-0.84; AUC difference, 0.06; 95% CI, 0.01-0.11; P<.01).
Discussion
In this study, we assessed the diagnostic power of LA strain to detect increased LV filling pressure in adults with COA. We observed that LA reservoir strain had superior diagnostic power to detect increased LV filling pressure (PAWP >12 mm Hg and LVEDP >16 mm Hg) as compared with LA booster strain, and other conventional echocardiographic indices of diastolic function (LA volume index, E/e', and tricuspid regurgitation velocity).
LA strain imaging provides a comprehensive assessment of LA and LV function at different phases of the cardiac cycle, with LA reservoir strain assessing LA compliance, LA conduit strain assessing LV relaxation and chamber stiffness, and LA booster strain assessing intrinsic LA contractility and LV end-diastolic compliance.11,14 Studies conducted in patients with acquired heart disease have demonstrated a correlation between LA strain and LV filling pressure.15-17 In a multicenter study of 322 adult patients with acquired heart disease who underwent same-day echocardiogram and cardiac catheterization (simultaneous studies in 90 patients), Inoue et al15 demonstrated that LA reservoir strain <18% and LA booster strain <8% provided the optimal cut-off point to identify patients with increased LV filling pressure, defined as PAWP >12 mm Hg or LVEDP >16 mm Hg. In a different study involving 76 patients with acquired heart disease who underwent same-day echocardiogram and left heart catheterization, Singh et al13 demonstrated that LA reservoir strain had a good correlation with pre-A wave LV diastolic pressure and that LA reservoir strain <20% had superior diagnostic power to detect increased LV filling pressure defined pre-A wave LV diastolic pressure >15 mm Hg (AUC, 0.76) as compared with the ASE/EACVI multiparametric algorithm for diastolic function assessment. Consistent with these prior studies from the acquired heart disease population, we observed that LA reservoir strain had good correlation with LV filling pressure and identified patients with increased LV filling pressure with superior diagnostic power as compared with other echocardiographic indices of LV diastolic function.
The prognostic role of LA reservoir strain is well described in patients with cardiovascular disease.9,11,13,21,22 In a previous study, we demonstrated that LA function (as measured by LA reservoir strain) was associated with transplant-free survival and had superior prognostic power as compared with LV diastolic function assessment based on the ASE/EACVI algorithm.23 The current study builds on this foundation and extends our knowledge about the role of LA straining imaging for estimating LV filling pressures in this population. We postulate that the diagnostic power of LA strain for detecting high LV filling pressure may be related to the central role of the LA in modulating LV filing.14,24
Clinical implications and future directions. An accurate assessment of LV filling pressure is important for risk stratification in patients with cardiovascular disease. This is because LV filling pressure is a critical link in the pathogenesis of atrial fibrillation and heart failure.14, 24 The results of the current study provide empirical validation of the cut-off points (LA reservoir strain <18% and LA pump strain <8%) proposed by Inoue et al15 for the detection of increased LV filling pressure in acquired heart disease. These estimates can potentially be used to guide medical therapy and to determine the timing of surgical and interventional therapies in the COA population. Cardiac catheterization is still the gold standard for the assessment of LV filling pressures, but LA strain could be used to improve patient selection for cardiac catheterization based on the results of the current study.
Study limitations. This is a retrospective, single-center study of patients with COA referred for cardiac catheterization and hence it is prone to selection and ascertainment bias. Since the patients referred for cardiac catheterization are typically “sicker,” the clinical characteristics of our cohort would therefore differ from those of other COA patients seen in the ambulatory clinic, which may limit the generalizability of the results. Finally, the loading conditions at the time of echocardiogram may be different from the loading conditions at the time of cardiac catheterization, since both tests were not performed simultaneously.
Conclusion
LA reservoir strain and LA booster strain have good correlation with LV filling pressure and can identify patients with increased LV filling pressure, with superior diagnostic power as compared with conventional echocardiographic indices of LV diastolic function in patients with COA. These data suggest that LA strain can potentially be used to identify patients likely to have increased LV filling pressures, thereby increasing the yield of cardiac catheterization in this population. Further studies are required to determine whether the use of these LA strain cut-off points in clinical decision making would improve clinical outcomes in this population.
Affiliations and Disclosures
From the Department of Cardiovascular Medicine, Mayo Clinic Rochester, Minnesota.
Funding: Dr Egbe is supported by National Heart, Lung, and Blood Institute (NHLBI) grants (R01 HL158517 and R01 HL160761). The MACHD Registry is supported by the Al-Bahar Research grant.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript accepted July 8, 2022.
Address for correspondence: Alexander Egbe, MD, MPH, FACC, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905. Email: egbe.alexander@mayo.edu
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