Reverse remodeling of left atrium assessed by cardiovascular magnetic resonance feature tracking in hypertrophic obstructive cardiomyopathy after septal myectomy

The medical records of 211 consecutive patients with HOCM, who received CMR before and after surgical myectomy at Fuwai Hospital between January 2011 and June 2021, were retrospectively identified. All patients met diagnostic criteria and surgical indications for HOCM according to the guidelines [3]. The indications for surgical myectomy were mainly (1) severe symptoms, syncope or near-syncope despite optimal medical therapy, and (2) resting or provoked LVOT pressure gradient ≥ 50 mmHg. The detailed recruitment is shown in Fig. 1. The major exclusions were: (1) interval of preoperative CMR before surgery greater than 6 months and interval of postoperative CMR after surgery less than 3 months, (2) patients with uninterpretable image quality caused by the onset of arrhythmia including AF during CMR examination, (3) relevant comorbidities (e.g. congenital heart disease, valvular disease, coronary artery disease [coronary artery stenosis ≥ 30% at invasive coronary angiography or coronary computed tomography angiography], hypertension, infiltrative cardiomyopathy), (4) patients who underwent Maze surgery, septal ablation before myectomy, and redo myectomy. Finally, a total of 88 patients formed the study cohort. LVOT pressure gradient, mitral regurgitation (MR), and transmitral E/A ratio were assessed by echocardiography within 2 weeks before or after the pre- and postoperative CMR. According to Doppler echocardiographic criteria [14], including color flow MR jet, continuous wave signal of MR jet, vena contracta width, effective regurgitant orifice area, etc., MR was graded as 0 (none), 1 (mild), 2 (moderate), or 3 (severe). In addition, 86 healthy controls of similar age and sex without known cardiovascular or systemic disease were selected from our database for comparison [15]. The study conformed to the principles of the Helsinki Declaration, and the hospital institutional review board approved this study. Due to the retrospective design of this study, written informed consent was waived for patients with HOCM, and this study was granted permission by Fuwai Hospital to use clinical and imaging data of study population.

Images were acquired using 3 T CMR scanners (Ingenia, Philips Healthcare, Best, the Netherlands) with retrospective electrocardiographic (ECG) gating and 32-channel cardiac coil before and after myectomy. All patients (including 10 patients with a history of AF) were in sinus rhythm during pre- and postoperative image acquisition. Standard transverse and sagittal dark blood images were obtained using a semi-Fourier single-shot sequence with the following parameters: section thickness = 8 mm, section gap = 4 mm, matrix size = 224 × 192, field of view = 340 × 280 mm, repetition time = 2 heartbeats, echo time = 40 ms. Cine images (LV two- and four-chamber view and sequential short-axis planes covering the entire ventricles) were acquired using a balanced steady-state free precession sequence with typical parameters as follows: section thickness = 8 mm, section gap = 2 mm, matrix size = 224 × 256, field of view = 380 × 380 mm, repetition time = 2.8 ms, echo time = 1.4 ms, temporal resolution = 30–55 ms (depends on heart rate). The late gadolinium enhancement (LGE) images were obtained 10–15 min after intravenous administration of gadolinium-DTPA at a dose of 0.2 mmol/kg by using a segmented phase-sensitive inversion recovery Turbo FLASH sequence at the same position as cine images in end-diastole with the following parameters: matrix size = 256 × 162, field of view = 380 × 320 mm, slice thickness = 8 mm, slice gap = 2 mm, repetition time = 6.1 ms, echo time = 3 ms, flip angle = 25°, nominal inversion time = 300 ms.

All measurements were performed blind to the clinical and investigative data. To avoid measurement bias, the reader made postprocessing analysis in a random order rather than continuously processing pre- and postoperative study of the same patient. Quantitative LV measurements were obtained as described previously [16]. Briefly, using a postprocessing workstation (Intellispace portal, Philips), LV ejection fraction (LVEF), LV end-diastolic volume index, LV end-systolic volume index, stroke volume, cardiac index, and LV mass index were measured by drawing LV endocardial and epicardial contours (excluding papillary muscles) on a stack of LV short-axis cines. Maximum wall thickness and LGE percentage were measured offline with CVI42 (v. 5.1, Circle Cardiovascular Imaging, Calgary, Canada) (Additional file 1).

LA parameters were determined as previously described [17, 18]. LA anteroposterior and left–right diameters were measured on transverse dark blood images. Phasic volume, strain, and strain rate measurements of LA were obtained from FT (QStrain, Medis Suite 3.2, Leiden, the Netherlands). After determining the identical line connecting the mitral annulus and the most distal wall of the LA at its maximum and minimum volume on two- and four-chamber cines, LA endocardial borders were automatically delineated at LV end-systole and end-diastole (Fig. 2A). If necessary, manual adjustments were performed to exclude pulmonary veins and LA appendage and to attain optimal tracking. After being processed using the tracking algorithm, the contours were automatically propagated in all frames. Typical LA deformation parameter curves in a healthy subject are depicted in Fig. 2B. Three aspects of LA global strain were calculated: εs (total strain reflects LA reservoir function during LV systole), εe (passive strain reflects LA conduit function during early LV diastole), and εa (active strain reflects LA booster function during late LV diastole). Corresponding phasic strain rates were SRs (peak positive strain rate), SRe (peak early negative strain rate), and SRa (late peak negative strain rate), respectively.

Volumetric indices of phasic LA function were also obtained at LV end-systole (maximum LA volume [LAV_max]), at LV diastole before LA contraction (passive LA volume [LAV_pac]), and at the late LV end-diastole after LA contraction (minimum LA volume [LAV_min]) [17, 18]. LA phasic emptying fractions (EF) were calculated as follows:

All patients underwent an extended Morrow procedure performed by the same cardiac surgeon with 22 years of experience in cardiac surgery. As previously described [19, 20], a standard median sternotomy was performed following the cardiopulmonary bypass with ascending aortic cannulation and bicaval cannulation; Abnormal anatomic structures leading to LVOT obstruction, including hypertrophic septum myocardium and anomalous chordal attachments, were corrected. Elongated leaflets were not routinely folded unless severe MR or systolic anterior motion remained after resection. Mitral valve repair or replacement was performed if necessary. Fourteen patients received mitral valve repair (see Additional file 2: Table S1 for more detailed data on mitral valve repair), and no other concomitant surgeries were performed. The goal was to reduce the LVOT pressure gradient to less than 30 mmHg and to lower MR degree to none or mild, as confirmed by intraoperative transesophageal echocardiography.

Statistical analyses were performed in SPSS (version 25.0, Statistical Package for the Social Sciences, International Business Machines, Inc., Armonk, New York, USA). Data were tested for normal distribution using the Shapiro–Wilk test, histograms, and Q–Q plots. Continuous data are expressed as mean ± standard deviations (SD) or as the median [interquartile range (IQR)] for variables with normal or non-normal distributions, respectively. Categorical data are presented as numbers and percentages. Parameters at baseline and follow-up CMR were compared using paired T-test or paired Wilcoxon signed-ranks test. Comparisons between different groups were performed using the independent samples t-test or Mann–Whitney U test for continuous variables, Chi‐square test or Fisher’s exact test for categorical variables. Associations of different continuous variables were examined by Pearson correlation coefficient or Spearman’s rank correlation coefficient (r). The delta value (Δ) equals the preoperative value minus the postoperative value. The rate of change is defined as the ratio of the delta value (Δ) to the preoperative value. Univariate and multivariate linear regression analyses (enter models) were used to find the potential variables associated with the rate of change of εa. Only those with a probability value < 0.05 by univariate analysis were entered in the multivariate model as covariates. Twenty subjects (including six healthy controls, seven premyectomy, and seven postmyectomy patients) were randomly selected from the entire cohort for the intra- and interobserver reproducibility assessment of LA parameters by the intra-class correlation coefficient (ICC) and Bland–Altman analyses. The intraobserver measurements were re-analyzed after 2 weeks. A two-sided P value < 0.05 was considered to indicate statistical significance.

The baseline characteristics of 88 patients with HOCM are summarized in Table 1. The mean age at surgery was 44 ± 13 years old and about half were men (52%). The prominent symptom was chest tightness (71%). 86 healthy controls with similar demographic features were included for comparison (Table 1). Preoperative CMR was performed at a median of 14 days (IQR, 6 to 33 days) before myectomy. The interval between the pre- and postmyectomy CMR was at a median of 1.14 years (IQR, 1.01 to 1.56 years).

The correlations between LA deformation parameters and LA conventional parameters are demonstrated in Fig. 6. Except for the correlation between preoperative εa and preoperative LA passive EF (r = 0.14, P = 0.46), almost all preoperative LA strains and strain rates were significantly correlated with preoperative LA conventional structural and functional parameters to various degrees (Fig. 6A). Nevertheless, postoperative correlations appeared to weaken, as most correlation coefficients were reduced after myectomy (Fig. 6B). Notably, the correlation between LA phasic deformation parameter and the corresponding LA phasic empty fraction was strongest both before and after myectomy.

Linear regression results are displayed in Table 4. Considering the collinearities among LA structural variables, we only included LAV_min index in linear regression analysis because of its highest correlation coefficient (r) with εa (from Fig. 6). In univariate analysis, systolic blood pressure, LAV_min index, ΔMR degree, and ΔLVOT pressure gradient were significantly associated with the rate of change of εa (all P < 0.05). In multivariate analysis, LAV_min index (adjusted β = − 0.39, P < 0.001) and ΔLVOT pressure gradient (adjusted β = − 0.29, P = 0.003) were significantly and independently related to the rate of change of εa.

A detailed overview of the intra- and interobserver reproducibility of LA parameters derived from CMR-FT is displayed in Table 5 and Fig. 7. FT yielded excellent reliability (intraobserver ICC: 0.90 to 0.99; interobserver ICC: 0.88 to 0.99). Overall, Bland–Altman analyses showed better reproducibility for FT on the intraobserver level than the interobserver level, as evidenced by 95% limits of agreement. LAV_min index had the best reproducibility with the narrowest limits of agreement among LA volumetric parameters, and so did LA booster EF among LA emptying fractions.

Several limitations of this study must be recognized. First, there might be a selection bias as we excluded patients who hadn’t received either preoperative or postoperative CMR, primarily due to the long waiting time (average of 4 weeks) for CMR examination in our tertiary referral center. Second, our study population was limited, but to our knowledge, it was the largest cohort focusing on the changes in LA examined by CMR. Third, we did not make a prognosis analysis because of the small number of hard clinical events. Our patient inclusion time range was broad (approximately 10 years), and 47% of patients underwent myectomy after 2018, so their short-term outcomes were generally favorable. Forth, given the reported good–excellent inter-scan reproducibility of LA FT using long-axis cines [36‐39], the inter-scan reproducibility was not tested in this study. Based on the relatively inferior scan-rescan reproducibility of LA phasic strain rates observed in previous study, our results on LA phasic strain rates should be interpreted with caution. Fifth, LA size was measured by bi-plane method, which is suboptimal to three-dimensional assessment from a short-axis stack covering LA. However, LA biplane assessment provides a reliable and applicable alternative to the time-consuming reference standard, and LA biplane parameters strongly correlate to those derived from Simpson’s methods [40]. Last, owing to the inherent drawbacks of retrospective study design, only transmitral E/A < 1 was available in this study among parameters of diastolic dysfunction assessed by echocardiography or cardiac catheterization. Prospective studies are needed to explore the correlation between diastolic function and LA deformation parameter.