Identification of heart failure with preserved ejection fraction in patients with hypertension: a left atrial myocardial strain cardiac magnetic resonance study
Original Article

Identification of heart failure with preserved ejection fraction in patients with hypertension: a left atrial myocardial strain cardiac magnetic resonance study

Jinyang Wen1,2, Xin Zhang1, Shuhao Li1, Xinwei Tao3, Qimin Fang1, Shuli Zhou1, Liming Xia2#, Lianggeng Gong1#

1Department of Radiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China; 2Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 3Bayer Healthcare, Shanghai, China

Contributions: (I) Conception and design: X Zhang, L Gong; (II) Administrative support: L Xia; (III) Provision of study materials or patients: S Li, S Zhou; (IV) Collection and assembly of data: J Wen, Q Fang; (V) Data analysis and interpretation: J Wen, Q Fang, X Tao; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work for the senior authorship.

Correspondence to: Lianggeng Gong. Department of Radiology, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, Nanchang 330006, China. Email: gong111999@126.com; Liming Xia. Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China. Email: xialiming2017@outlook.com.

Background: The noninvasive diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. The role of left atrial (LA) functional changes in patients with HFpEF has attracted increased attention. This study aimed to evaluate LA deformation in patients with hypertension (HTN) using cardiac magnetic resonance tissue tracking and to investigate the diagnostic value of LA strain for HFpEF.

Methods: This retrospective study consecutively enrolled 24 HTN patients with HFpEF (HTN-HFpEF) and 30 patients with pure HTN based on clinical indications. Thirty age-matched healthy participants were also enrolled. All participants underwent a laboratory examination and 3.0 T cardiovascular magnetic resonance (CMR). The LA strain and strain rate, including total strain (εs), passive strain (εe), active strain (εa), peak positive strain rate (SRs), peak early negative strain rate (SRe), and peak late negative strain rate (SRa), were evaluated using CMR tissue tracking and compared among the 3 groups. Receiver operating characteristic (ROC) analysis was used to identify HFpEF. Spearman correlation was used to analyze the correlation between LA strain and brain natriuretic peptide (BNP) level.

Results: Patients with HTN-HFpEF had significantly lower εs (17.70%, IQR 14.65% to 19.70%, εe 7.83%±2.86%), εa (9.08%±3.19%), SRs (0.88±0.24 s−1), SRe (−0.60 s−1, IQR −0.90 to −0.50 s−1), and SRa (−1.10±0.47 s−1) than did patients with HTN and control participants (all P values <0.05). Compared to the control group, patients with HTN had lower εs (25.35%, IQR 21.80% to 27.25%), εe (11.49%±2.64%), SRs (1.10 s−1, IQR 1.00 to 1.48 s−1), and SRe (−1.11±0.37 s−1) (all P values <0.05). The values of εa and SRa were not significantly different between the HTN and control groups. LA total strain εs was independently associated with HFpEF (odds ratio 0.009; P<0.05) with a cutoff value of 19.55% (95% CI: 0.882–0.996), and the sensitivity and specificity were 75% and 97%, respectively. There was a good correlation between the LA strain parameters and BNP level (all P values <0.05).

Conclusions: LA function impairment exists in patients with HFpEF. The LA strain parameter has potential value in diagnosing HFpEF.

Keywords: Hypertension (HTN); heart failure with preserved ejection fraction (HFpEF); left atrial (LA); myocardial strain; cardiac magnetic resonance imaging (cardiac MRI)


Submitted Sep 23, 2022. Accepted for publication Mar 01, 2023. Published online Mar 16, 2023.

doi: 10.21037/qims-22-1012


Introduction

Heart failure with preserved ejection fraction (HFpEF) accounts for 50% of all cases of heart failure and has become a severe threat to public health problems in recent years (1,2). Several risk factors have been proven to be related to HFpEF, such as age (≥60 years old), obesity [body mass index (BMI) >30 kg/m2], hypertension (HTN), atrial fibrillation, and diabetes (3-6), among which HTN is dominant (7). Left ventricular (LV) diastolic dysfunction is known to be a main pathological change in patients with HFpEF (8-10). Left atrial (LA) function (including reservoir, conduit, and pump functions) is crucial for regulating LV filling in the LV diastole phase (10,11). Some studies have shown that the impairment of LA function exists in HTN patients with HFpEF (12,13), and LV diastolic dysfunction may lead to LA dysfunction. Others have demonstrated that LA strain has a strong correlation with LV filling pressure (14). Due to this close relationship between LA function and LV diastolic function, the impairment of LA function in patients with HFpEF has also attracted attention. Despite these valuable researches on HFpEF, a noninvasive and accurate diagnosis method for HFpEF is still a challenge in clinical practice. Whether the LA strain parameter can help to detect HFpEF needs to be determined with further exploration.

Cardiovascular magnetic resonance tissue tracking (CMR-TT) is a quantitative technique for tracking tissue voxel motion in a standard steady-free precession movie image, which can accurately track myocardial movements and quantify the degree of myocardial deformation (15,16). LV strain analysis is the most widely applied type of analysis performed using CMR-TT, but the quantification of LA deformation using CMR-TT has also been demonstrated to have excellent feasibility and reproducibility (17,18).

Our study aimed to explore the differences in LA myocardial dysfunction among HTN patients with HFpEF (HTN-HFpEF), patients with pure HTN, and healthy participants and to investigate the potential value of LA strain derived from CMR in diagnosing HFpEF. We hypothesized that LA strains are impaired in HTN-HFpEF patients, and LA strain parameters can be used to detect HFpEF. We present the following article in accordance with the STARD reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1012/rc).


Methods

Study population

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the ethics board of the Second Affiliated Hospital of Nanchang University. All participants signed informed consent and accepted CMR and echocardiography examinations within 5 days. Eligible participants were included in the HTN-HFpEF group if they met the following criteria: (I) they were diagnosed with HTN clinically; (II) they presented with typical HF symptoms (e.g., palpitation, nervousness, chest congestion, and exercise intolerance) of New York Heart Association (NYHA) functional classes II or III; (III) the preserved LV ejection fraction (LVEF) >50% on echocardiography was present; and (IV) they had a score ≥5 according to the HFA-PEFF algorithm [echocardiographic and brain natriuretic peptide (BNP) score, functional testing in case of uncertainty, final etiology] (3). HTN was defined as office systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg (19). The exclusion criteria were as follows: (I) secondary HTN; (II) any underlying cardiomyopathy (hypertrophic, dilated, restrictive, amyloidosis, diabetic, etc.) or ischemic heart disease; (III) severe arrhythmia; (IV) primary moderate or severe valvular heart disease; (V) anemia or hyperthyroidism; and (VI) a previous history of myocardial infarction or heart surgery. All patients were enrolled consecutively between August 2018 and September 2021. HTN patients but without HFpEF were only clinically diagnosed with pure HTN, with the exclusion criteria similar to those of the first group. In addition, age-matched healthy controls whose relevant examination (clinical presentation, laboratory examination, imaging examination) proved to be normal were matched to the age of the patients with HTN. We calculated that the required sample size to be 75 according to the results of the pre-experiment on a small sample size of admitted patients under a significance level of 5% (2-sided). Therefore, the final sample size was sufficient.

Echocardiography protocol and analysis

A comprehensive 2-dimensional echocardiography study with conventional Doppler and tissue Doppler was performed using a commercially available system (Vivid E95 GE Healthcare, Boston, MA, USA). Mitral inflow and mitral annulus parameters were measured at rest from the apical 4-chamber view using conventional Doppler and tissue Doppler imaging. Echocardiographic parameters, including e' velocity and average septal-lateral E/e' ratio (AS-L E/e' ratio), were documented.

CMR protocol and analysis

All participants underwent a magnetic resonance imaging (MRI) protocol on a 3.0 T MRI scanner (Discovery 750W, GE Healthcare) with an 8-channel phase-array cardiac coil. Cardiac short-axis, 2-chamber, and 4-chamber view images were acquired using a standard breath-hold steady-state free precession cine sequence. The scan range contained the entire left atrium and left ventricle short-axis slices from the apex to the base. The scan parameters were as follows: 2-chamber and 4-chamber slice thicknesses, 5 mm and 3 slices; short-axis slice thickness, 6 mm and 8–12 slices; gap, 4 mm; repetition time (TR), 3.9 ms; echo time (TE), 1.6 ms; matrix size, 256×256; field of view (FOV), 360×360 mm; flip angle, 55°; and slice spacing, 0.

Cardiac VX software (Advance Workstation 4.6, GE Healthcare) was used to analyze cardiac function. The LV endocardial and epicardial were contoured in end-systolic and end-diastolic at the short-axis cine manually, and the software automatically tracked the above contours in other phases. Manual correction was made as needed. LV function parameters, including LV end-diastolic volume (LVEDV), LV end-systolic volumes (LVESV), LVEF, stroke volume (SV), and cardiac output (CO), were recorded.

LA volume analysis was performed using the cardiovascular image analysis software CVI42 (v.5.12; Circle Cardiovascular Imaging Inc., Calgary, Canada). The endocardial contours were detected manually at the end-diastolic phases in the 2-chamber and 4-chamber views, and excluded pulmonary veins and LA appendages. The contour could be adapted to other phases automatically. Manual correction was performed if necessary. The LA volume parameters were assessed, including the maximum LA volume (LAVmax), minimum LA volume (LAVmin), and volume before LA contraction (LAVpre). The left atrial volume index (LAVI) refers to the ratio of LA volume at the end of LV contraction to body surface area. The final value of the above parameter was obtained by averaging the values of the 2- and 4-chamber views. The LA ejection fraction was calculated from the LA volumes, including LA total ejection fraction (LATEF), LA passive ejection fraction (LAPEF), and LA active ejection fraction (LAAEF), using the following formula (20):

LATEF=LAVmaxLAVminLAVmax×100%

LAPEF=LAVmaxLAVpreLAVmax×100%

LAAEF=LAVpreLAVminLAVpre×100%

LA strain and strain rate analyses were performed using Tissue-Tracking in CVI42 software. The endocardial and epicardial contours were manually delineated in end-systolic and end-diastolic phases in the 2-chamber and 4-chamber views. Longitudinal time-strain curves and time-strain rate curves were obtained automatically. The following myocardial strain parameters were derived: total strain (εs), passive strain (εe), active strain (εa), peak positive strain rate (SRs), peak early negative strain rate (SRe), and peak late negative strain rate (SRa). These parameters were also the average values obtained on 2-chamber and 4-chamber views. The positive and negative values of strain represent the lengthening and shortening of the myocardium, respectively. εs and SRs reflect LA reservoir function, εe and SRe reflect LA conduit function, and εa and SRa reflect LA pump function (Figure 1) (18,21).

Figure 1 An example case of LA strain and strain rate parameters from a healthy participant, which was obtained by delineating the LA endocardial and epicardial contours. (A) End-diastolic phase in the 2-chamber view. (B) End-systolic phase in the 4-chamber view. (C) The LA strain curve. (D) End-systolic phase in the 2-chamber view. (E) End-diastolic phase in the 4-chamber view. (F) The LA strain rate curve. The red line represents the LA endocardial contour. The green line represents the LA epicardial contour. The purple line represents the atrioventricular junction line and the line between the posterior wall of the LA and the midpoint of the mitral valve. The yellow line is all LA global segment curves. εs and SRs reflect LA reservoir function, εe and SRe reflect LA conduit function, and εa and SRa reflect LA pump function. LA, left atrial; εs, total strain; εa, active strain; εe, passive strain; SRs, peak positive strain rate; SRa, peak late negative strain rate; SRe, peak early negative strain rate.

Data reproducibility

Radiologists XZ and JW (5 years of experience) analyzed LA strain in 54 patients with HTN. Two weeks later, radiologist JW with 5 years of experience repeated the same procedure. Two radiologists were blind to the clinical information of the patients with HTN. The intraobserver and interobserver variability of LA strain parameters was assessed using the intraclass correlation coefficient (ICC).

Statistical analysis

SPSS v. 23.0 (IBM Corp., Armonk, NY, USA) and R version 4.1.2 (The R Foundation for Statistical Computing, Vienna, Austria) were used to analyze all data. Normal distributions were assessed using the Kolmogorov-Smirnov test. Normally distributed variables are expressed as the mean ± standard deviation (SD), whereas nonnormally distributed variables are reported as medians with interquartile ranges (IQRs). Categorical data are expressed as a percentage. For comparisons between 2 groups, the Mann-Whitney test was used for continuous data comparisons, and Fisher exact test was used for categorical data comparisons as appropriate. One-way analysis of variance or Kruskal-Wallis test and chi-squared test were used to compare data between 3 groups, with the Bonferroni test being used for post hoc correction. Logistic regression was used to explore the association between the LA strain parameters and HFpEF-HTN. Receiver operating characteristic (ROC) curve analysis was performed to find the best cutoff value in distinguishing patients with HFpEF from patients with HTN with the detection of sensitivity and specificity at this cutoff value. The Spearman correlation coefficient was calculated and interpreted as follows: <0.5, weak; 0.5 to 0.8, moderate; and ≥0.8, strong. A P value <0.05 was considered statistically significant.


Results

Clinical characteristics

The enrollment flowchart is shown in Figure 2. Our study consecutively enrolled 24 patients with HTN-HFpEF, 30 patients with pure HTN only, and 30 healthy volunteers. Of these, 57/84 (67.9%) were male, and the mean age of the patients was 57.35±11.40 years. The mean BMI value was 24.81±3.13 kg/m2. The mean log-transformed BNP value was 3.88±2.47 pg/L. Of the 84 patents, 57 were male (19, 25, and 13 in the HTN-HFpEF, HTN, and control groups, respectively) with a median age of 65.5, 56, and 56 years in the HTN-HFpEF, HTN, and control groups, respectively. Other clinical characteristics details are displayed in Table 1.

Figure 2 Flowchart of the study population enrollment. MRI, magnetic resonance imaging; HFpEF, heart failure with preserved ejection fraction; HTN, hypertension.

Table 1

Clinical characteristics

Characteristics HTN-HFpEF (n=24) HTN (n=30) Control (n=30) P value
Male, n (%) 19 (79.17)b 25 (83.33)b 13 (43.33) 0.002
Age, years 65.50 [52.75, 69.50] 56 [44.75, 65.00] 56 [53, 57] 0.064
Body mass index, kg/m2 24.23±2.99b 25.99±3.89b 23.09±2.44 0.003
Body surface area, m2 1.71±0.19b 1.82±0.20b 1.66±0.15 0.004
Systolic blood pressure, mmHg 159.54±21.34b 145.8±20.73b 120.63±7.71 <0.001
Diastolic blood pressure, mmHg 89 [71.50, 99.25]b 85 [80.50, 94.50]b 73 [66.25, 78.00] <0.001
Heart rate, bpm 66.50 [62, 74] 71 [65, 78] 74 [69.25, 77.50] 0.055
History of hypertension, years 6 [2, 10] 3 [2, 7] 0.241
Hypertension classification, n (%) 0.422
   III/IV 14 (25.90) 15 (27.80)
   I/II 10 (16.70) 15 (18.50)
NYHA functional class, n (%) <0.001
   IV 0 (0) 0 (0)
   III 3 (12.50) 1 (3.33)
   II 21 (87.50) 13 (43.33)
   I 0 (0) 16 (53.33)
Log-transformed BNP, pg/L 6.80±1.30a 4.02±1.27b 1.42±1.10 <0.001

The data are presented as n (%), the mean ± standard deviation or median with interquartile range. a, P<0.05 vs. controls and HTN group; b, P<0.05 vs. controls. HTN-HFpEF, hypertension with heart failure with preserved ejection fraction; HTN, hypertension; NYHA, New York Heart Association; BNP, brain natriuretic peptide.

LV functional parameters from echocardiography and CMR

The e' velocity was the lowest in the HTN-HFpEF group, followed by the HTN and healthy control groups. The E/e' was also significantly different among the 3 groups. There were no significant differences in CMR parameters. The details are displayed in Table 2.

Table 2

LV parameters from CMR and echocardiography

Characteristics HTN-HFpEF (n=24) HTN (n=30) Control (n=30) P value
CMR parameters
   LVEF, % 64.33±6.68 64.37±7.53 63.70±3.71 0.862
   CO, L/min 4.20 (3.01, 4.94) 4.54 (3.66, 5.61) 4.09 (3.77, 4.56) 0.540
   LVESV, mL 38.35 (24.73, 48.12) 31.85 (25.05, 46.60) 33.45 (28.95, 36.72) 0.686
   LVEDV, mL 102 (80.28, 116.62) 100.25 (78.88, 125.25) 92.6 (82.55, 99.50) 0.260
   SV, mL 63.75 (51.85, 80.45) 64.30 (50.60, 77.12) 58.1 (51.73, 62.70) 0.277
Echocardiography parameters
    e' velocity, cm/s 4.94±0.98a 5.78±1.82b 11.76±2.18 <0.001
    E/e' 13.41 (10.86, 16.40)a 10.2 (8.78, 12.69)b 5.57 (5.02, 5.76) <0.001

The data are presented as the mean ± standard deviation or median with interquartile range. a, P<0.05 vs. controls and HTN group; b, P<0.05 vs. controls. CMR, cardiac magnetic resonance; HTN-HFpEF, hypertension with heart failure with preserved ejection fraction; HTN, hypertension; LVEF, left ventricular ejection fraction; CO, cardiac output; LVESV, left ventricular end-systolic volume; LVEDV, left ventricular end-diastolic volume; SV, stroke volume; e' velocity, early diastolic mitral annulus velocity; E/e', early diastolic mitral inflow velocity/early diastolic mitral annulus velocity.

LA volume parameters from CMR

The LA volume parameters in the 3 groups are listed in Table 3. The differences in LATEF and LAPEF among the HTN-HFpEF, HTN, and healthy participants were statistically significant (all P values <0.05), showing an increasing trend.

Table 3

LA volume parameters from CMR

Characteristics HTN-HFpEF (n=24) HTN (n=30) Control (n=30) P value
LATEF, % 47.59±8.91a 57.88±6.03b 67.46±4.59 <0.001
LAPEF, % 20.65±7.29a 29.03±5.36b 41.47±5.64 <0.001
LAAEF, % 26.99 (21.54, 32.68) 28.71 (24.28, 33.88) 24.81 (22.26, 29.75) 0.113
LAVmax, mL 72.11 (63.89, 90.93)b 61.24 (52.02, 80.94)b 48.62 (42.99, 55.51) <0.001
LAVmin, mL 36.67 (30.73, 48.83)a 26.91 (20.69, 30.98)b 15.62 (13.22, 17.56) <0.001
LAVI, mL/m2 41.73 (35.88, 53.67)a 35.45 (29.42, 41.84) 29.43 (26.13, 35.15) <0.001

The data are presented as the mean ± standard deviation or median with interquartile range. a, P<0.05 vs. controls and HTN group; b, P<0.05 vs. controls. LA, left atrial; CMR, cardiac magnetic resonance; HTN-HFpEF, hypertension with heart failure with preserved ejection fraction; HTN; hypertension; LATEF, left atrial total ejection fraction; LAPEF, left atrial passive ejection fraction; LAAEF, left atrial active ejection fraction; LAVmax, maximum of left atrial volume; LAVmin, minimum of left atrial volume; LAVI, left atrial volume index.

No significant difference in LAAEF was found among the 3 groups. The LAVmax values in patients with HTN-HFpEF and HTN were significantly higher than those in controls, but no difference was found between patients with HTN-HFpEF and those with HTN. The LAVmin was the highest in the HTN-HFpEF group, followed by the HTN and healthy groups [all P values <0.05; LAVmin (mL): 36.67 (30.73, 48.83) vs. 26.91 (20.69, 30.98) vs. 15.62 (13.22, 17.56)]. LAVI was higher in patients with HTN-HFpEF than in those with HTN and control participants (both P values <0.05).

LA strain parameters derived from CMR-TT and identification of HTN-HFpEF

The LA strain and strain rate parameters in the 3 groups are listed in Table 4. Patients with HTN-HFpEF had the lowest all LA strain parameters among the 3 groups. Patients with HTN had significantly lower εs, εe, SRs, and SRe than did controls (Figure 3).

Table 4

LA strain and strain rate parameters from CMR

Parameters HTN-HFpEF (n=24) HTN (n=30) Controls (n=30) P value
εs, % 17.70 (14.65, 19.70)a 25.35 (21.80, 27.25)b 39.28±7.57 <0.001
εa, % 9.08±3.19a 13.49±4.30 14.99±3.90 <0.001
εe, % 7.83±2.86a 11.49±2.64b 24.29±6.26 <0.001
SRs, s−1 0.88±0.24a 1.10 (1.00, 1.48)b 1.83±0.43 <0.001
SRa, s−1 −1.10±0.47a −1.67±0.56 −1.95 (−2.23, −1.48) <0.001
SRe, s−1 −0.60 (−0.90, −0.50)a −1.11±0.37b −2.20 (−2.48, −1.90) <0.001

The data are presented as the mean ± standard deviation or median with interquartile range. a, P<0.05 vs. controls and HTN group; b, P<0.05 vs. controls. LA, left atrial; CMR, cardiac magnetic resonance; HTN-HFpEF, hypertension with heart failure with preserved ejection fraction; HTN, hypertension; εs, total strain; εe passive strain; εa, active strain; SRs, peak positive strain rate; SRa, peak late negative strain rate; SRe, peak early negative strain rate.

Figure 3 Comparisons of LA strain and strain rate among the HTN-HFpEF, HTN, and control groups. (A) LA strain εs in the 3 groups. (B) LA strain εa in the 3 groups. (C) LA strain εe in the 3 groups. (D) LA strain rate SRs in 3 groups. (E) LA strain rate SRa in the 3 groups. (F) LA strain rate SRe in the 3 groups. n=24 HTN-HFpEF; n=30 HTN; n=30 control. *, P<0.05; **, P<0.01; ***, P<0.001. εs, total strain; εa, active strain; εe, passive strain; SRs, peak positive strain rate; SRa, peak late negative strain rate; SRe, peak early negative strain rate; HTN-HFpEF, hypertension with heart failure with preserved ejection fraction; HTN, hypertension; ns, not significant; LA, left atrial.

The logistic regression analysis was conducted only for hypertensive patients (patients with HTN-HFpEF and HTN). The εs, εa, εe, SRs SRa, and SRe were significantly correlated with the diagnosis of HFpEF. Nevertheless, in multivariable logistic regression analysis with the aforementioned variables, only εs remained independently associated with the diagnosis of HFpEF [odds ratio: 0.009 per SD increase; 95% CI: 0.000–0.433; P<0.05; Table 5]. In the ROC curve analysis, εs yielded an area under the curve (AUC) of 0.939. With a cutoff value of 19.55% (95% CI: 0.882–0.996), the sensitivity was 75%, and the specificity was 97%. We compared the results of ROC analysis for several LA volume and echocardiographic parameters (Figure 4 and Table 6). The results of the comparison of clinical and εs diagnoses are shown in Table 7.

Table 5

Logistic regression analysis with LA strain variables

Parameters Univariate Multivariate
OR value 95% CI P value OR value 95% CI P value
εs, per SD increase 0.018 0.002–0.196 0.001 0.009 0.000–0.433 0.017
εa, per SD increase 0.225 0.091–0.557 0.001 0.624 0.024–15.999 0.776
εe, per SD increase 0.227 0.094–0.547 0.001
SRs, per SD increase 0.175 0.060–0.512 0.001 2.432 0.423–13.899 0.321
SRa, per SD increase 3.584 1.625–7.745 0.001 0.836 0.101–6.938 0.868
SRe, per SD increase 4.718 1.898–11.727 0.001 4.816 0.843–27.521 0.077

The logistic regression analysis was conducted only for patients with hypertension (with and without HFpEF). LA, left atrial; OR, odds ratio; εs, total strain; εa, active strain; εe passive strain; SRs, peak positive strain rate; SRa, peak late negative strain rate; SRe, peak early negative strain rate; SD, standard deviation; HFpEF, heart failure with preserved ejection fraction.

Figure 4 ROC curves 6 parameters in the differentiation of patients with HTN-HFpEF from patients with HTN. (A) The ROC curve of εs. (B) The ROC curve of E/e'. (C) The ROC curve of e'. (D) The ROC curve of LAVI. (E) The ROC curve of LATEF. (F) The ROC curve of LAPEF. TPR, true positive rate; FPR, false positive rate; AUC, area under the curve; εs, total strain; E/e', early diastolic mitral inflow velocity/early diastolic mitral annulus velocity; e', early diastolic mitral annulus velocity; LAVI, left atrial volume index; LATEF, left atrial total ejection fraction; LAPEF, left atrial passive ejection fraction; ROC, receiver operating characteristic; HTN-HFpEF, hypertension with heart failure with preserved ejection fraction; HTN, hypertension.

Table 6

The comparison of the ROC analysis

Variables AUC 95% CI Sensitivity (%) Specificity (%) Cutoff value
εs, % 0.939 0.882–0.996 75 97 19.550
e' velocity, cm/s 0.641 0.493–0.789 100 30 6.350
E/e' 0.715 0.578–0.852 83 57 10.370
LAVI, mL/m2 0.738 0.606–0.869 96 40 32.363
LATEF, % 0.832 0.722–0.942 75 83 52.486
LAPEF, % 0.831 0.714–0.947 79 83 25.519

ROC, receiver operating characteristic; AUC, area under the curve; εs, total strain; e' velocity, early diastolic mitral annulus velocity; E/e', early diastolic mitral inflow velocity/early diastolic mitral annulus velocity; LAVI, left atrial volume index; LATEF, left atrial total ejection fraction; LAPEF, left atrial passive ejection fraction.

Table 7

The results of the comparison of clinical and εs diagnosis

Category εs (clinical diagnosis) Total Fisher P value
≤19.55% >19.55%
With HFpEF 18 6 24 <0.0001
Without HFpEF 1 29 30
Total 19 35 54

εs, total strain; HFpEF, heart failure with preserved ejection fraction.

Correlation of LA strain parameters with BNP

Among the 3 groups, there were moderate or strong correlations between strain parameters and BNP (εs, r=−0.844; εa, r=−0.539; εe, r=−0.752; SRs, r=−0.652; SRa, r=0.545; SRe, r=0.756; Figure 5).

Figure 5 Correlations between LA strain parameters and BNP parameters. (A) The correlation between εs and BNP, (B) εa and BNP, (C) εe and BNP, (D) SRs and BNP, (E) SRa and BNP, and (F) SRe and BNP. BNP, brain natriuretic peptide; εs, total strain; εa, active strain; εe, passive strain; SRs, peak positive strain rate; SRa, peak late negative strain rate; r, correlation coefficient; HTN-HFpEF, hypertension with heart failure with preserved ejection fraction; HTN, hypertension; LA, left atrial.

Reproducibility assessment

All strain and strain rate parameters exhibited excellent intraobserver and interobserver consistency (ICC >0.85). The ICCs with 95% CIs for the LV strain parameters are summarized in Table 8.

Table 8

Intraobserver and interobserver LA strain parameters

Parameters Intraobserver Interobserver
ICC 95% CI ICC 95% CI
εs, % 0.980 0.971–0.989 0.982 0.972–0.989
εa, % 0.968 0.950–0.979 0.959 0.938–0.973
εe, % 0.968 0.950–0.979 0.947 0.909–0.968
SRs, s−1 0.935 0.869–0.964 0.960 0.934–0.975
SRa, s−1 0.968 0.950–0.980 0.982 0.969–0.989
SRe, s−1 0.952 0.924–0.970 0.956 0.932–0.971

LA, left atrial; ICC, intraclass correlation coefficient; εs, total strain; εa, active strain; εe, passive strain; SRs, peak positive strain rate; SRa, peak late negative strain rate; SRe, peak early negative strain rate.


Discussion

Our study provides a novel approach for identifying HFpEF in HTN patients based on reproducible CMR-TT-derived LA functional quantitative parameters. The correlation between LA myocardial strain parameters and BNP was confirmed.

In the current HFpEF diagnostic criteria, the E/e' ratio and LA size, which reflect LV diastolic function, have traditionally been assessed via echocardiography. However, the diagnostic accuracy decreases substantially when the E/e' ratio value is between 8 and 14 (22), meaning that the assessment of LV diastolic dysfunction only via E/e' ratio is limited and not entirely reliable. LAVI has been established as the only recommended parameter for evaluating LA morphological changes in clinical practice (3). LA strain, as an emerging parameter of LA function, was proven to be strongly correlated with LV end-diastolic filling pressure (23-25). It is a more sensitive marker than is LAVI for reflecting early impaired LA function (26,27). Studies have shown that echocardiographic LV global longitudinal strain and CMR-derived LV global peak systolic longitudinal rates could differentiate between patients with hypertensive heart disease and HFpEF. However, only a few publications have investigated subtle LA functional differences among HFpEF-HTN and HTN and control participants using CMR-TT strain analysis (28,29). The strengths of the current study are that we demonstrated that the subtle LA functional dynamic change with the progression of the LV diastolic dysfunction and CMR-derived LA reservoir strain could provide diagnostic value in HFpEF.

In our study, patients with HFpEF presented worse LA εs/SRs, εe/SRe, and εa/SRa than did controls, which was in accordance with the results of previous studies (13,30-32). Furthermore, εs, εe, SRs, and SRe among HFpEF-HTN, HTN, and the control participants showed significant differences with an increasing trend, but εa/SRa showed no statistical difference between the HTN and control participants. These findings indicated that LA reservoir and conduit function gradually decrease with the progression of LV diastolic dysfunction, while pump function impairment might occur later than the impairment of the reservoir and conduit function. According to the Frank-Starling mechanism, the reasonable explanation for this finding is that adaptive redistribution occurs along with hemodynamic changes to ensure LV filling and maintain cardiac function in the progression of LV diastolic dysfunction. Nevertheless, the compensatory effect is not unlimited, and eventually, the decompensation effect can cause a decrease in LA function (33). Of note, εs remained a significant predictor of HFpEF in the multivariable analysis, in line with previous studies using echography (12,34). Inoue et al. (35) found that the LA reservoir was determined predominantly by LV filling pressure. However, this cannot entirely explain why only εs is an imaging diagnostic marker of HFpEF in our study, as the LA reservoir phase occurs before LV diastole phase whereas conduit and pump phases occur during the LV diastole phase (36). We speculated that the LA reservoir was first impaired when LV diastolic dysfunction occurred. Therefore, εs may be the earliest detectable LA functional change in patients with HFpEF, but further studies are warranted to investigate the order in which LA change progresses after the occurrence of LV diastolic dysfunction. Beyond this, CMR-TT has high accuracy and repeatability and has been widely used to evaluate LA myocardial function in different cardiac diseases (37,38). All measurements in our study were also highly reproducible (ICC >0.9).

Our study found that LA strain parameters may be more sensitive than is LA ejection fraction in reflecting LA function impairment. LATEF, LAPEF, and LAAEF corresponded to LA reservoir, conduit, and pump functions, respectively. LA ejection fraction is an indicator of atrial systolic function and a useful parameter for ventricular diastolic function (39). Patients with HTN-HFpEF had the lowest LATEF and LAPEF, while there was no statistical significance in LAAEF among the 3 study groups. This result was consistent with that reflected by the LA strain parameters. It is worth noting that LA active strain was significantly different among the 3 groups, whereas LAAEF was not. Thus, the LA strain parameter may be more sensitive than the LA ejection fraction, which means the strain impairment precedes morphological LA changes in patients with HTN (26).

BNP is one of the functional biomarkers of HFpEF and is also known as a predictor of prognosis in patients with HFpEF; that is, it is highly correlated with hospitalization and mortality (40,41). Similar to the results of Abid et al.’s study (42), we also found that LA strain parameters were moderately or excellently correlated with BNP. Our study further demonstrates that CMR-derived LA strain parameters may provide useful functional information in evaluating LV diastolic dysfunction. Further studies are warranted to investigate the potential value of LA strain parameters in the prognosis of patients with HTN-HFpEF.

We acknowledge several limitations of our study. First, it is a preliminary study with a small sample size, especially of patients with HTN-HFpEF. Additionally, the study only involved a single center, and selection bias may exist. A large multicenter study is required to verify the reliability of the LA strain parameters. The BMI and sex of those with HTN and healthy participants were not matched, but there was no significant difference between patients with HTN-HFpEF and HTN. Finally, LAVI was replaced with CMR measurements as an inclusion standard, which is recommended in the European Society of Cardiology guidelines.


Conclusions

CMR-TT strain parameters are a promising method for evaluating LA deformation in patients with HTN and demonstrated correlations with functional parameters. LA total strain (εs) has potential value in discriminating patients with HFpEF from hypertensive patients.


Acknowledgments

The authors would like to thank Dr. Junhao Tu, from the First Affiliated Hospital of Nanchang University, for his insightful advice on data analysis.

Funding: This work was supported by the National Natural Science Foundation of China (Nos. 81873889 and 81860316).


Footnote

Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-22-1012/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1012/coif). XT is a current employee of Bayer Healthcare. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the ethics board of the Second Affiliated Hospital of Nanchang University, and individual consent for this retrospective analysis was obtained.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.


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Cite this article as: Wen J, Zhang X, Li S, Tao X, Fang Q, Zhou S, Xia L, Gong L. Identification of heart failure with preserved ejection fraction in patients with hypertension: a left atrial myocardial strain cardiac magnetic resonance study. Quant Imaging Med Surg 2023;13(5):2881-2894. doi: 10.21037/qims-22-1012

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