Association between ultrasound-quantified cardiac mechanical dyssynchrony and left heart function and remodeling

Introduction

Cardiac synchronization is crucial for maintaining heart function. Under the 2021 European Society of Cardiology (ESC) guidelines (1), cardiac resynchronization therapy (CRT) is recommended according to the patient’s electrical activity (QRS width), the presence of left bundle branch block (LBBB), and a left ventricular ejection fraction (LVEF) ≤35%. However, QRS-based electrical activity cannot identify all suitable patients. Moreover, a significant limitation of CRT is that 30–40% of patients show no improvement (2).

Intra-left ventricular (intra-LV) and interventricular (inter-V) mechanical dyssynchrony, which represent cardiac mechanical activity, are common in heart failure (HF) patients (3,4). Intra-LV dyssynchrony is associated with cardiac dysfunction and left ventricular (LV) remodeling; research has indicated that the redistribution of myocardial mechanics following CRT is an important factor contributing to reverse remodeling (5,6). Other studies have confirmed that the standard deviation of the time to peak longitudinal strain according to speckle-tracking echocardiography (SD_STE) effectively predicts the response of patients with intra-LV mechanical dyssynchrony to CRT (7,8).

Most previous studies have analyzed the effect of intra-LV or inter-V mechanical dyssynchrony on the efficacy of CRT or cardiac function and remodeling separately (9-13). The present study was innovative in that the research simultaneously evaluated different combinations of intra-LV or inter-V mechanical synchrony or dyssynchrony in patients with chronic heart failure (CHF). On the basis of the 2011 expert consensus (14), this study evaluated intra-LV or inter-V mechanical synchrony or dyssynchrony using the standard deviation of the time to peak longitudinal strain in 12 LV segments according to speckle-tracking echocardiography (SD_12STE) and interventricular mechanical delay (IVMD) measured by tissue Doppler. The CHF patients were categorized into the following four groups: the intra-LV and interventricular synchrony (Intra_sInter_s) group; the intra-LV synchrony and interventricular dyssynchrony (Intra_sInter_ds) group; the intra-LV dyssynchrony and interventricular synchrony (Intra_dsInter_s) group; and the intra-LV and interventricular dyssynchrony (Intra_dsInter_ds). Speckle-tracking echocardiography (STE) was used to obtain the left atrial (LA) and LV functional parameters. Echocardiographic parameters, QRS width, N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels, and other parameters were analyzed to understand the differences in and characteristics of left heart function and remodeling in these patients. Cardiac events that occurred during patient follow up were also investigated to determine which combined synchrony state had the worse cardiac prognosis. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2024-2554/rc).

Methods

Study population

This was a single-center retrospective study of patients with CHF who visited the First Affiliated Hospital of Xinjiang Medical University from December 2019 to June 2023. A total of 208 patients who were diagnosed with CHF according to the 2021 ESC guidelines (15) and had a LVEF <50% were included in the study. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional ethics board of the First Affiliated Hospital of Xinjiang Medical University (No. K/2024/02-12). As the study was retrospective, the requirement for informed consent was waived by the institutional ethics board. Patients were excluded from the study if they met any of the following exclusion criteria: had congenital heart disease, moderate to severe organic valvular heart disease, moderate to severe pulmonary arterial hypertension, right ventricular myocardial disease, severe liver dysfunction, a pacemaker, and images of insufficient quality for analysis. Additionally, 52 volunteer subjects with no abnormal findings in their clinical history or on physical examination, electrocardiography, or echocardiography were included in the control group.

The clinical data and medical history of all the included subjects were retrieved from their electronic medical records, and the QRS width was recorded as the time from the first deviation of the QRS complex to the end of the equipotential component on electrocardiogram. The NT-proBNP level on the first day after admission was recorded, as was the occurrence of cardiac events (16). The primary event was the worsening of HF, which was characterized by pacemaker implantation due to HF, the need for radiofrequency ablation for arrhythmia, or rehospitalization due to clinical cardiac decompensation. These events were recorded from the date of inclusion to the final follow-up date (February 29, 2024).

Grouping criteria

Intra-LV mechanical dyssynchrony was defined as per the 2011 Echocardiographic Techniques for the Quantitative Evaluation of Cardiac Mechanics consensus (14) as a SD_12STE of >60 ms, and inter-V mechanical dyssynchrony was defined as an IVMD (the time difference between the mechanical activation of the basal segment of the right ventricular lateral wall and that of the last segment of the LV lateral wall) of >56 ms on tissue Doppler imaging (14,17). The patients were allocated to the following groups: the Intra_sInter_s group (n=58), the Intra_sInter_ds group (n=40), the Intra_dsInter_s group (n=51), and the Intra_dsInter_ds group (n=59) (Figure 1).

Figure 1 Research flowchart. CHF, chronic heart failure; ED, end-diastole; GLS, global longitudinal strain; IVMD, interventricular mechanical delay; Intra_sInter_s, intra-left ventricular and interventricular synchrony; Intra_sInter_ds, intra-left ventricular synchrony and interventricular dyssynchrony; Intra_dsInter_s, intra-left ventricular dyssynchrony and interventricular synchrony; Intra_dsInter_ds, intra-left ventricular and interventricular dyssynchrony; LAScd, left atrial conduit strain; LASct, left atrial contractile strain; LASr, left atrial reservoir strain; LA, left atrial; LV, left ventricular; LVEF, left-ventricular ejection fraction; NT-proBNP, N-terminal pro-B-type natriuretic peptide; SD_12STE, standard deviation of the time to peak longitudinal strain in 12 left-ventricular segments according to speckle-tracking echocardiography.

Transthoracic echocardiography

An EPIQ 7C ultrasound system (Philips Medical Systems, Andover, MA, USA) was used for the echocardiographic assessment. As per the guidelines of the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) (14,18), standard images were recorded, the electrocardiograms were synchronously connected, and two-dimensional images of the apical four-chamber, apical two-chamber, and apical long-axis views over five consecutive cardiac cycles were acquired and stored. The collected Digital Imaging and Communications in Medicine-format echocardiographic images were transferred to a QLAB Quantification Software (Philips Ultrasound, Inc., Washington, USA). The time from mitral valve opening to closure in the mitral flow spectrum in the apical four-chamber view was defined as the LV filling time (LV-FT). The cardiac cycle spanned one R-wave peak to the next on the electrocardiogram was defined as R-R interval. The LV-FT/R-R interval was calculated as a percentage of the cardiac cycle; a value <40% indicated atrioventricular dyssynchrony (19).

STE analysis

The echocardiographic images were analyzed offline using QLAB software (Philips Ultrasound, Inc.). Although we referenced the SD_12STE at the basal and mid-ventricular levels in the 2011 consensus (14), to obtain the overall myocardial strain value, the strain of 18 LV segments was comprehensively evaluated. As per the EACVI and ASE guidelines (17), LV strain was measured in the apical four-chamber, apical two-chamber, and apical long-axis views by manually tracing the endocardium and obtaining a bull’s eye plot of the 18 myocardial segments, and the GLS was recorded. LA strain was obtained from apical four-chamber and two-chamber views at a frame rate of 50–70 frames/second via two-dimensional AutoStrain mode as per the EACVI and ASE guidelines (20). LA reservoir strain (LASr) was calculated as the strain at mitral valve opening minus the strain at LV end-diastole (yielding a positive value). LA conduit strain (LAScd) was calculated as the strain at the onset of atrial contraction minus the strain at mitral valve opening (yielding a negative value). LA contractile strain (LASct) was calculated as the strain at LV end-diastole minus the strain at the onset of atrial contraction (yielding a negative value). To avoid ambiguity, all the strain parameters were converted to absolute values.

Interobserver and intraobserver reproducibility

Image analysis and reproducibility analysis were conducted by physicians with over 10 years of extensive experience. The same physician re-analyzed the images of 20 randomly selected subjects after a 2-week washout period to assess intraobserver variability. Another physician who was blinded to the first results of the first physician re-analyzed the images of the same subjects to evaluate interobserver variability. The Bland-Altman test was used to quantify interobserver and intraobserver variability.

Statistical analysis

The SPSS 27.0 software package (SPSS Inc., Chicago, IL, USA) was used for the statistical analysis of all the data. The normally distributed and homoscedastic data are presented as the mean ± standard deviation, and a one-way analysis of variance was used for multiple-group comparisons. The non-normally distributed or heteroscedastic data are presented as the median (interquartile range), and the Kruskal-Wallis test was used for multiple-group comparisons. Post-hoc analysis with Bonferroni correction was performed to identify between-group differences when significant differences were found in the multiple-group analyses. The categorical data are presented as the number (percentage), and their differences were analyzed with the Chi-squared test or Fisher’s exact test. A Spearman correlation analysis was conducted. The determinants of GLS, LASr, LAScd, and LASct were selected according to the results of the univariable linear regression analyses and physiological rationality. A multivariable linear regression analysis was subsequently employed to identify independent predictors for these parameters. The Kaplan-Meier method was used to analyze hospitalization due to the development of worsening cardiac events by drawing event-free survival curves for the four groups. Differences between the survival curves were evaluated using the log-rank test and Breslow test, with a particular focus on the early and late stages of the survival curves. All the statistical tests were two-tailed with α=0.05, and a P value <0.05 was considered statistically significant.

Results

Clinical characteristics

Of the 208 patients with CHF included in the study, 160 were male, 48 were female, and they had an average age of 59.9±12.6 years. The control group comprised 32 males and 20 females, and had an average age of 60.79±13.3 years. The clinical characteristics of the subjects in each group are summarized in Table 1, while the clinical characteristics and treatment distributions of the subjects in the CHF groups are summarized in Table 2. There were no significant differences among the CHF groups in terms of the history of atrial fibrillation, history of premature ventricular contraction, or presence of right bundle branch block (P>0.05). The QRS width, NT-proBNP level, and heart rate values were similar among the Intra_sInter_s, Intra_sInter_ds, and Intra_dsInter_s groups (P>0.05). Compared with the other CHF groups, the Intra_dsInter_ds group had a greater QRS width (Figure 2A) and was more likely to have LBBB (37.3%). Additionally, the natural logarithm [LN (NT-proBNP)] (Figure 2B) level was greater in the Intra_dsInter_ds group than the Intra_sInter_s and Intra_sInter_ds groups (P<0.05). The heart rate of the Intra_sInter_ds group was lower than that of the other CHF groups (P<0.05). The proportions of patients with New York Heart Association (NYHA) class III/IV heart function who received β-blockers and angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blocker (ARBs) were greater in the Intra_dsInter_s and Intra_dsInter_ds groups than the Intra_sInter_s group (P<0.05). The proportion of patients receiving loop diuretics/aldosterone blockers was greater in the Intra_dsInter_s and Intra_dsInter_ds groups than the Intra_sInter_s and Intra_sInter_ds groups (P<0.05).

Figure 2 QRS width, LN (NT-proBNP), and LVEDVI differences among groups. (A) Differences in the QRS width in the five groups. (B) Differences in LN (NT-proBNP) in the four CHF groups. (C) Differences in LVEDVI in the five groups. *, P<0.05 versus control; ^†, P<0.05 versus Intra_sInter_s; ^‡, P<0.05 versus Intra_sInter_ds; ^§, P<0.05 versus Intra_dsInter_s. Intra_sInter_s, intra-left ventricular and interventricular synchrony; Intra_sInter_ds, intra-left ventricular synchrony and interventricular dyssynchrony; Intra_dsInter_s, intra-left ventricular dyssynchrony and interventricular synchrony; Intra_dsInter_ds, intra-left ventricular and interventricular dyssynchrony; LN, natural logarithm; NT-proBNP, N-terminal pro-B-type natriuretic peptide; LVEDVI, left ventricular end-diastolic volume index.

Echocardiographic characteristics

Table 3 shows the echocardiographic parameters of each group. Both LV diastolic and LV systolic function were lower in all CHF groups than the control group (P<0.05). Similarly, the LA and LV volume parameters were greater in all CHF groups than the control group (P<0.05). There were no statistically significant differences among the CHF groups in terms of LV diastolic function, left-atrial volume (LAV), left-atrial volume index (LAVI), or the proportion of moderate/severe mitral regurgitation (P>0.05). The LV end-diastolic volume index (LVEDVI) and LV end-systolic volume index (LVESVI) were greater in the intra-LV dyssynchrony groups than the Intra_sInter_s group, while the Intra_dsInter_ds group had the highest LVEDVI among the CHF groups (P<0.05) (Figure 2C). Compared with the intra-LV synchrony groups (Intra_sInter_s and Intra_sInter_ds), the intra-LV dyssynchrony groups (Intra_dsInter_s and Intra_dsInter_ds) had a lower LVEF and greater proportions of patients with a LVEF ≤35% (Figure 3A). The LV-FT/R-R was lower in the CHF groups than the control group; the only exception was the Intra_sInter_ds group, which had a higher LV-FT/R-R than the other CHF groups, as well as the lowest proportion of patients with atrioventricular dyssynchrony (5.1%).

Figure 3 Differences between the LV function and LA function among the five groups. (A) Proportions of LVEF in the four groups. (B) Changes in GLS in the five groups. (C) Differences in the LASr in the five groups. (D) Differences in the LASct in the five groups. (E) Differences in LAScd in the five groups. *, P<0.05 versus control; ^†, P<0.05 versus Intra_sInter_s; ^‡, P<0.05 versus Intra_sInter_ds. Intra_sInter_s, intra-left ventricular and interventricular synchrony; Intra_sInter_ds, intra-left ventricular synchrony and interventricular dyssynchrony; Intra_dsInter_s, intra-left ventricular dyssynchrony and interventricular synchrony; Intra_dsInter_ds, intra-left ventricular and interventricular dyssynchrony; GLS, global longitudinal strain; LAScd, left atrial conduit strain; LASct, left atrial contractile strain; LASr, left atrial reservoir strain; LA, left atrial; LV, left ventricular; LVEF, left-ventricular ejection fraction.

LA and LV strain echocardiographic characteristics

The STE parameters are shown in Table 4. The GLS was lower in the CHF groups than the control group, but it did not differ between the two intra-LV synchrony groups, and the two intra-LV dyssynchrony groups (P>0.05). However, the GLS was lower in the intra-LV dyssynchrony groups than the intra-LV synchrony groups (P<0.001) (Figure 3B).

The LASr, LAScd, and LASct were lower in the CHF group than the control group, but all three were similar between the intra-LV synchrony groups (P>0.05) and between the intra-LV dyssynchrony groups (P>0.05). The LASr and LASct values were lower in the intra-LV dyssynchrony groups than the Intra_sInter_ds group (Figure 3C,3D) (P<0.001), and the LAScd values were lower in the intra-LV dyssynchrony groups than the intra-LV synchrony groups (P<0.001) (Figure 3E).

Relationship of LA function and LV function with the SD_12STE and IVMD

In the bivariate correlation analyses, the SD_12STE and IVMD were significantly correlated with the GLS (Figure 4A), LASr (Figure 4B), LVEDVI (Figure 4C), and QRS width (Figure 4D) (r=−0.79, −0.55, 0.61, and 0.53, respectively, and −0.36, −0.15, 0.44, 0.39, respectively; P<0.05); and the correlations were stronger for the SD_12STE than the IVMD. After adjusting for the LASr, LAVI, LVESVI, ratio of the early filling wave to the early diastolic mitral annular velocity (E/e'), QRS width, heart rate, and LV-FT/R-R, the multivariable linear regression analysis revealed that only the SD_12STE was independently associated with GLS (R²=0.834, β=−0.256, P<0.001), while the IVMD did not independently predict GLS (P>0.05) (Table 5). After adjusting for the LAVI, LVESVI, E/e', QRS width, heart rate, and LV-FT/R-R, only the GLS was independently associated with LASr (R²=0.794, β=0.644, P<0.001) (Table S1), while the SD_12STE and IVMD were not independent predictors of this parameter. The multivariable analysis results for LASct and LAScd showed that after adjusting for the LAVI, LVESVI, E/e', QRS width, heart rate, and LV-FT/R-R, only the GLS was independently associated with LASct and LAScd, respectively (P<0.001) (Tables S2,S3).

Figure 4 The relationship between the SD_12STE, IVMD, GLS, LVEDVI, and QRS. (A) The relationship between the SD_12STE, IVMD, and GLS. (B) The relationship between the SD_12STE, IVMD, and LASr. (C) The relationship between the SD_12STE, IVMD, and LVEDVI. (D) The relationship between the SD_12STE, IVMD, and QRS. GLS, global longitudinal strain; IVMD, interventricular mechanical delay; LASr, left atrial reservoir strain; LVEDVI, left-ventricular end-diastolic volume index; SD_12STE, standard deviation of the time to peak longitudinal strain in 12 left-ventricular segments according to speckle-tracking echocardiography.

Outcome analysis

The follow-up data regarding cardiac events are shown in Table 4. The follow-up period was 1.15 years (interquartile range, 0.92–2.16 years), during which no patient died. A total of 137 patients (65.8%) reached the composite endpoint of hospitalization due to HF [32 (55.1%) in the Intra_sInter_s group, 21 (52.5%) in the Intra_sInter_ds group, 35 (68.6%) in the Intra_dsInter_s group, and 49 (83.0%) in the Intra_dsInter_ds group]. A total of 107 patients (51.4%) were implanted with a pacemaker, 13 patients (6.2%) underwent radiofrequency ablation for arrhythmia, and 17 patients (8.2%) were re-hospitalized solely for medical treatment due to cardiac decompensation. The proportion of cardiac events was greater in the Intra_dsInter_ds group than the other CHF groups (P<0.001). There was no statistically significant difference in the proportions of patients who received dual-chamber pacing therapy or single-chamber pacing therapy among the CHF groups (P>0.05). Compared with those in the Intra_sInter_s and Intra_dsInter_s groups, a greater proportion of patients in the Intra_dsInter_ds group received CRT (P<0.05).

The Kaplan-Meier analysis revealed that the incidence of cardiac events was similar between the Intra_sInter_s, Intra_sInter_ds and Intra_dsInter_s groups (Figure 5) (P>0.05), while. the Intra_dsInter_ds group had a greater incidence of cardiac events than the Intra_sInter_s, Intra_sInter_ds groups (P<0.05) (Figure 5). The different CHF groups in this study all comprised patients with very poor heart function, which made them prone to early-onset heart events; thus, the survival curves of our HF group were relatively steep in the early stages.

Figure 5 Kaplan-Meier curves of event-free survival according to the type of CHF. *, P<0.05 versus Intra_dsInter_ds. CHF, chronic heart failure; Intra_sInter_s, intra-left ventricular and interventricular synchrony; Intra_sInter_ds, intra-left ventricular synchrony and interventricular dyssynchrony; Intra_dsInter_s, intra-left ventricular dyssynchrony and interventricular synchrony; Intra_dsInter_ds, intra-left ventricular and interventricular dyssynchrony.

Reproducibility

In terms of the intraobserver reproducibility of the strain observations, the 95% limits of agreement for the LASr and GLS biases were −0.26±3.52 and 0.45±1.81, respectively. In terms of the interobserver reproducibility of the strain observations, the 95% limits of agreement for the LASr and GLS biases were −0.16±2.66 and 0.15±1.82, respectively. The intraobserver and interobserver reproducibility of the LASr, LAScd, LASct, and GLS was acceptable. Bland-Altman plots for the intraobserver and interobserver reproducibility of all strains are shown in Figures S1,S2.

Discussion

Synchronized heart movement is crucial in maintaining normal cardiac function. In this study, CHF patients were categorized into four groups on the basis of the combination of intra-LV and inter-V mechanical synchrony or dyssynchrony. STE was employed to describe the trends and characteristics of LA and LV function in these four groups, and the relationship between cardiac mechanical dyssynchrony and left heart function was analyzed. The key findings were as follows: (I) intra-LV dyssynchrony is more strongly associated with LV dysfunction and remodeling than inter-V dyssynchrony is; (II) LA function is heavily dependent on LV function; and (III) the cooccurrence of intra-LV and inter-V dyssynchrony exacerbates LV remodeling, leading to a greater incidence of adverse cardiac events in these patients.

STE technology can be employed to accurately quantify myocardial function (21). Our findings indicated that the GLS and LVEF were more deteriorated in the intra-LV dyssynchrony groups than the intra-LV synchrony groups, which is consistent with the findings of Kumar and Goel (22), who reported that HF patients with higher rates of intra-LV dyssynchrony have poorer left heart function. Walters et al. (6) found that the extent of cardiomyopathy was associated with intra-LV dyssynchrony, which is consistent with our findings. The bivariable correlation analysis revealed a significant association between both the intra-LV mechanical index (SD_12STE) and the IVMD with LV function, with the former variable demonstrating a stronger correlation. The multivariable linear regression analysis further confirmed that the SD_12STE was more strongly associated with LV function than the IVMD. This may be a critical reason why the IVMD parameter has been reported to have limited predictive value for CRT success (10-12). The anomalously low GLS observed in the intra-LV dyssynchrony group (Table 4) is attributable to the method used to compute this parameter, whereby the absolute values of strain were averaged across all segments during systole. The occurrence of paradoxical motion in some segments within these two cohorts resulted in positive strain values during systole, resulting in an abnormally low overall average. The LA is crucial for maintaining effective LV filling and cardiac output, and LA function has emerged as a powerful predictor of cardiovascular events (23,24). The LA cycle consists of a reservoir phase, a conduit phase, and a contractile pump phase. When LV function is normal, the reservoir and conduit phases comprise 40% and 35% of the LA cycle, respectively, while the contractile pump phase comprises the remaining 25% (25). When the LV diastolic function is disrupted, the conduit function weakens, whereas the reservoir and contractile pump functions are strengthened. LA strain is largely influenced by the GLS (26), and as HF progresses, LA strain decreases (27,28). In progressive HF with restrictive filling patterns, the gradual loss of LA contractile pump function leads to the dominance of conduit function, which explains why the LAScd of the intra-LV dyssynchrony groups was lower than that of the intra-LV synchrony groups. Additionally, in the Intra_sInter_ds group, the reservoir and contractile pump function was better than that in the intra-LV dyssynchrony groups. After adjusting for heart rate (given that it was lower in the Intra_sInter_ds group than the other CHF groups) and factors affecting LA function (Tables S1-S3), the multivariable linear regression analysis revealed that LA function was closely related to GLS. Therefore, the results of this study suggest that LA function is associated primarily with LV function.

Outcomes of patients with different types of CHF

In late-stage congestive HF, intraventricular conduction block leads to QRS wave widening, which, in addition to LV volume enlargement, are characteristics of cardiac remodeling. These cardiac remodeling features, as well as LBBB, are closely associated with poor cardiac outcomes (29,30). NT-proBNP is a common biomarker for assessing HF severity (31). Among the two intra-LV dyssynchrony groups, patients with concomitant inter-V dyssynchrony presented wider QRS waves, greater LVEDVI values, a greater likelihood of LBBB, higher NT-proBNP levels, and a greater incidence of cardiac events despite similar levels of LV and LA function, and a greater proportion ultimately underwent CRT during follow up. Sami et al. (32) reported a higher incidence of intra-LV dyssynchrony in HF patients with LBBB. Fauchier et al. (33) found that a reduction in LV function was more common in patients with intra-LV dyssynchrony than in patients with inter-V dyssynchrony among patients with dilated cardiomyopathy, while Bader et al. (16) reported that in HF patients without myocardial infarction, intra-LV dyssynchrony independently predicted adverse cardiac events. Our study provides a new perspective on the combination of intra-LV and inter-V mechanical dyssynchrony or synchrony, addressing the shortcomings of previous reports. Intra-LV dyssynchrony was found to be more related to LV dysfunction and LV remodeling than inter-V dyssynchrony; however, the combination of the two was more significantly associated with the LV volume and cardiac electrical remodeling, leading to more severe cardiovascular events. However, the relationship between cardiac electromechanical factors appears to have both overlapping and independent components, as some patients had a normal QRS wave width and mechanical dyssynchrony. This aligns with the results of Ghio et al.’s study (4), which indicated that inter-V and intra-LV dyssynchrony are common in HF patients regardless of QRS duration.

Study limitations

This study had several limitations. As a single-center study, it had a small sample size; therefore, the results must be considered preliminary. Future studies should aim to include a larger sample size and data from multiple centers. The use of a more reliable prospective design to validate the results is also recommended. Further, this study did not include patients with heart failure with preserved ejection fraction (HFpEF). During patient screening, we observed that patients with HFpEF also exhibited either the Intra_sInter_s or Intra_sInter_ds synchronicity combinations, but not the Intra_dsInter_s or Intra_dsInter_ds combinations. Therefore, the conclusions drawn from this study cannot be extrapolated to all HFpEF patients, and further research needs to be conducted to examine LV and LA function in these individuals. According to the current guidelines (34), the echocardiographic measurement of cardiac dyssynchrony parameters is not recommended when evaluating CRT patients. The use of the SD_12STE in our study may seem somewhat outdated, but the preliminary results of this study appear to be clinically useful. Although the cardiac mechanical dyssynchrony evaluated in this study has potential value in screening CRT candidates, further research is needed to determine the prognostic value of CRT treatment for different combinations of cardiac mechanical dyssynchrony. In this study, the relationships between different combinations of intra-LV and inter-V synchrony or dyssynchrony and right heart function were not investigated, and thus represent a direction for further research. STE itself has several limitations, such as variability between device manufacturers, dependence on good image quality, operator experience, frame rate settings, load conditions, and external mechanical factors. In particular, a concave chest wall structure can pose challenges in imaging; individuals with a concave chest wall structure and/or even slight forms of pectus excavatum often present with intraventricular and/or inter-V dyssynchrony, even in the absence of any intrinsic myocardial functional impairment. Therefore, it is crucial to ensure strict quality control of STE studies (35-38).

Conclusions

Compared with inter-V mechanical delay, intra-LV dyssynchrony is more strongly associated with LV functional decline and structural remodeling, and LA dysfunction is largely dependent on LV dysfunction. Although the levels of LA and LV function were similar between patients with intra-LV dyssynchrony and inter-V synchrony, patients with concurrent intra-LV and inter-V dyssynchrony demonstrated the most pronounced LV volumetric increases and electrocardiographic remodeling. Over a follow-up period of 1.15 years (interquartile range, 0.92–2.16 years), the incidence of cardiac events in intra-LV and inter-V dyssynchrony group was higher than intra-LV synchrony groups, and they were more frequently candidates for CRT. Our findings suggest that the results of the echocardiographic assessment of cardiac mechanical dyssynchrony are intricately linked to LA and LV function and morphology. Various combinations of intra-LV and inter-V mechanical synchrony or dyssynchrony produce different levels of LA and LV functional and structural impairment, and knowledge of these differences is critical for clinical diagnostics, therapeutic strategy formulation, and patient management.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2024-2554/rc

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2024-2554/coif). The 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 and its subsequent amendments. The study was approved by the institutional ethics board of the First Affiliated Hospital of Xinjiang Medical University (No. K/2024/02-12). As the study was retrospective, the requirement for informed consent was waived by the institutional ethics board.

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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