Role of myocardial strain parameters in assessing indications for pulmonary valve replacement in children after tetralogy of Fallot repair: a cross-sectional study

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BACKGROUND

Tetralogy of Fallot is the most common cyanotic congenital heart defect and is characterized by four primary features: a ventricular septal defect, obstruction of the right ventricular (RV) outflow tract, RV myocardial hypertrophy, and dextroposition of the aorta [1].

In the mid-20th century, only 20% of children with congenital heart defects survived to adulthood. Currently, because of advances in pediatric cardiac surgery, mortality has significantly decreased, and most patients with tetralogy of Fallot now survive to 60 years of age [2, 3]. However, in growing children who have undergone radical repair of the defect, the risk of late complications persists, including the development of heart failure, pulmonary artery stenosis, infective endocarditis, impaired growth and development, the need for repeated interventions, and the occurrence of arrhythmias [4]. Surgical treatment of tetralogy of Fallot is aimed at eliminating RV outflow tract stenosis and closing the ventricular septal defect. If there is marked hypoplasia of the pulmonary valve annulus, extensive infundibulectomy and transannular patching are required, leading to the development of severe pulmonary regurgitation [5]. This results in chronic RV volume overload, causing progressive RV dilation and dysfunction. Subsequently, this is accompanied by the development of atrial and ventricular arrhythmias and also increases the risk of sudden cardiac death [5–11].

An effective method for treating pulmonary insufficiency in patients after radical repair of tetralogy of Fallot is timely pulmonary valve replacement using a bioprosthesis or conduit, which promotes remodeling and improvement of RV function [12, 13]. Established indications for pulmonary valve replacement include the presence of arrhythmias, decreased exercise tolerance, worsening New York Heart Association (NYHA) functional class, severe pulmonary artery stenosis, and progressive tricuspid regurgitation in combination with moderate to severe pulmonary regurgitation [14]. However, the optimal timing of valve replacement in asymptomatic patients remains a subject of debate [15–18].

Cardiac magnetic resonance imaging (MRI) is considered the gold standard for visualization and assessment of RV volume and function in patients with repaired tetralogy of Fallot [19–21]. Threshold values for RV end-diastolic volume (EDV) ranging from 150–170 mL/m² are considered a criterion for pulmonary valve replacement in asymptomatic patients [12, 17, 22] and are believed to be the most reliable single predictor of the need for surgery.

Nevertheless, unresolved questions remain regarding determination of the optimal timing for pulmonary valve replacement in patients after radical repair of tetralogy of Fallot in the absence of clinical symptoms. In addition, there are no studies evaluating myocardial contractile and relaxation function of both ventricles in younger children after surgical repair of tetralogy of Fallot using MRI as a tool to predict the need for pulmonary valve replacement.

AIM

To assess myocardial strain parameters as a criterion supporting the need for pulmonary valve replacement.

METHODS

Study Design

This was a single-center, retrospective (medical record review–based), cross-sectional study.

Study Setting

The study included data from patients treated in the Departments of Cardiothoracic Surgery and Cardiology of the National Research Cardiac Surgery Center in Astana, Kazakhstan. Cardiac MRI was performed after surgical repair of tetralogy of Fallot between December 2011 and June 2020.

Eligibility Criteria

Inclusion criteria:

• Children aged 3–18 years after radical repair of tetralogy of Fallot; and
• Availability of cardiac MRI results, laboratory blood test results [measurement of the cardiac biomarker N-terminal pro–B-type natriuretic peptide (NT-proBNP)], and echocardiography (Echo) results (pressure gradient between the RV and the pulmonary artery).

Exclusion criteria:

• Elevated serum creatinine concentration; and
• Patients older than 18 years with unrepaired tetralogy of Fallot.

Study Duration

Data analysis was performed from October 2011 to December 2020.

Cardiac Magnetic Resonance Imaging

Cardiac MRI was performed using a Magnetom Avanto® 1.5T superconducting magnetic resonance scanner (Siemens Healthcare, Germany) in a basic configuration. Scanning was performed with mandatory prospective electrocardiographic and respiratory synchronization, using a Spin Echo pulse sequence for anatomical assessment. In infants and children younger than 3 years, examinations were performed on an empty stomach under intravenous anesthesia according to the standard protocol adopted at the National Research Cardiac Surgery Center, under anesthesiologist supervision. Images were acquired in 3 standard planes (transverse axial, sagittal, and frontal), in planes analogous to 4- and 2-chamber projections on Echo, and in oblique planes according to zones of interest when required by study objectives.

Assessment of Heart Failure Severity

Blood NT-proBNP concentration was measured using enzyme immunoassay or chemiluminescent immunoassay methods. NT-proBNP is a biomarker used to diagnose and assess the severity of heart failure. Echo was performed to determine the pressure gradient between the RV and the pulmonary artery.

Main Study Outcome

To determine the prognostic significance of myocardial strain indices when making decisions regarding the timing of pulmonary valve replacement.

Outcomes Registration

Feature tracking (strain)¹ was performed using Segment CMR® software (Lund, Sweden). Basal, midventricular, and apical short-axis slices of the left ventricle (LV) and RV, as well as the 4-chamber slice, were selected for analysis. Using the rewind tool, the moments of end-diastole and end-systole were identified, after which the endocardial and epicardial contours were manually traced. Peak global circumferential strain of the LV and RV was calculated as a weighted average (by number of segments) of the peak circumferential strain values of the basal, midventricular, and apical levels. To assess longitudinal strain of the LV, endocardial and epicardial contours were additionally drawn on the 2- and 4-chamber projections. Peak global longitudinal strain of the LV and RV was determined from the 4-chamber projection. The results were exported into a Word document, where the peak values of global circumferential and longitudinal strain were recorded.

Group Analysis

Because RV EDV values of 150 to 170 mL/m² are considered an indication for pulmonary valve replacement in asymptomatic patients [12, 17, 22], the study sample was divided into 2 groups according to EDV value:

• Group 1: patients with RV EDV < 150 mL/m²; or
• Group 2: patients with RV EDV ≥ 150 mL/m².

Ethics Approval

The study was approved by the Ethics Committee of the National Research Cardiac Surgery Center (approval No. 01-92/2021, dated April 22, 2021). All participants provided written informed consent to participate in the study.

Statistical Analysis

The samples size was not calculated previously.

Statistical analysis was performed using STATA® version 16.2 (StataCorp LLC, USA). Descriptive statistics were used to characterize study participants. Most variables were continuous and therefore are presented as M ± SD, where M is the mean value and SD is the standard deviation. Categorical variables are presented as absolute numbers and percentages. To compare continuous variables between groups, the Student t-test or Mann–Whitney U test was used, depending on whether assumptions for the parametric test were met. For the categorical variable sex, the Fisher exact test was applied because the assumptions for using the χ² test were not satisfied in the 2 × 2 contingency table for groups stratified by RV EDV. The critical significance level was set at p = 0.05.

RESULTS

Sample Characteristics

A total of 69 patients aged 3 to 18 years (11 ± 4 years) who previously underwent radical repair of tetralogy of Fallot were enrolled. Of these, 24 (35%) were girls and 45 (65%) were boys (see Table 1). In the study sample, 52 patients (75%) had an RV EDV <  150 mL/m² and comprised group 1, whereas 17 patients (25%) with an RV EDV ≥ 150 mL/m² comprised group 2. The mean RV EDV differed significantly by sex: 116.8 ± 26.9 and 137.2 ± 20.9 mL/m² in girls and boys, respectively (p = 0.001).

 

Table 1. Sample characteristics (n = 69)
Characteristics	Value
Age, years	11 ± 4
Pressure gradient between the right ventricle and pulmonary artery, mm Hg	19.7 ± 13.7
N-terminal pro–B-type natriuretic peptide concentration, pg/mL	186 ± 196.2
Right ventricular end-diastolic volume, mL/m2	130.1 ± 24.9
Right ventricular end-diastolic volume <  150 mL/m2, n (%)	52 (75)
Right ventricular end-diastolic volume ≥ 150 mL/m2, n (%)	17 (25)
Right ventricular end-systolic volume, mL/m2	68.5 ± 60.3
Right ventricular ejection fraction, %	52.5 ± 7.4
Left ventricular end-diastolic volume, mL/m2	72.9 ± 14.5
Left ventricular end-systolic volume, mL/m2	28 ± 8.3
Left ventricular ejection fraction, %	62.2 ± 5.7
Note. Quantitative data are presented as M ± SD, where M is the mean value and SD is the standard deviation.

 

A comparison of the main patient characteristics based on RV EDV is presented in Table 2. Although there were no statistically significant differences in sex distribution, group 2 included a smaller proportion of females (18%) compared with males (82%). The RV end-systolic volume (ESV) in group 1 was approximately two-fold lower than in group 2, p <  0.001 (see Table 2).

 

Table 2. Comparative analysis of the main patient characteristics by group according to right ventricular end-diastolic volume
Characteristics	Group 1, n = 52	Group 2, n = 17	p
Age, years	11 ± 3	10 ± 4	0.518
Sex (female/male), n (%)	21 (40)/31 (50)	3 (18)/14 (82)	0.075
Pressure gradient between the right ventricle and pulmonary artery, mm Hg	18.5 ± 12.5	23.5 ± 16.6	0.379
N-terminal pro–B-type natriuretic peptide concentration, pg/mL	174.1 ± 195.2	222.7 ± 200.7	0.201
Right ventricular end-systolic volume, mL/m2	56.9 ± 19.1	103.9 ± 111.9	< 0.001
Right ventricular ejection fraction, %	52.5 ± 7.5	52.2 ± 7.4	0.839
Left ventricular end-diastolic volume, mL/m2	72.1 ± 16.1	75.3 ± 7.7	0.129
Left ventricular end-systolic volume, mL/m2	27.9 ± 8.9	28.1 ± 5.9	0.626
Left ventricular ejection fraction, %	62.1 ± 5.5	62.5 ± 6.2	0.829
Note. Quantitative data are presented as M ± SD, where M is the mean value and SD is the standard deviation.

 

NT-proBNP concentrations were slightly higher in group 2; however, no statistically significant differences were observed between the groups (Tables 2 and 3). This may suggest that RV dilation in these patients is not accompanied by a marked increase in cardiac load, or that biomarker concentrations vary depending on individual patient characteristics. Sex and the pressure gradient between the RV and the pulmonary artery did not differ significantly. The RV and LV ejection fractions remained preserved and demonstrated no significant differences between groups (Table 2).

 

Table 3. Comparison of right ventricular strain parameters between groups according to right ventricular end-diastolic volume
Right ventricular region	Group 1, n = 52	Group 2, n = 17	p
Global circumferential strain, %	−17.1 ± 3.8	−16.9 ± 3.9	0.728
Global longitudinal strain, %	−17.5 ± 3.2	−17.9 ± 3.9	0.268
Circumferential strain, %
Free wall	−18.2 ± 3.9	−18.1 ± 4.1	0.722
Septum	−17.7 ± 4.1	−17.2 ± 3.7	0.813
Longitudinal strain, %
Free wall	−20.4 ± 3.5	−20.5 ± 4.1	0.728
Septum	−15.4 ± 3.2	−16.1 ± 4.3	0.573
Note. Quantitative data are presented as M ± SD, where M is the mean value and SD is the standard deviation.

 

Primary Results

A comparative analysis of LV strain parameters between groups based on RV EDV is presented in Table 4. Circumferential strain in the basal anteroseptal segment of the LV demonstrated statistically significant differences between groups (p = 0.003). Significant differences were also observed in the basal inferior LV segment (p = 0.014).

 

Table 4. Comparison of left ventricular strain parameters between groups according to right ventricular end-diastolic volume
Left ventricular region	Group 1, n = 52	Group 2, n = 17	p
Peak global circumferential strain, %	−21.2 ± 3.5	−20.6 ± 1.5	0.326
Global longitudinal strain, %	−14.1 ± 3.5	−14.9 ± 3.7	0.531
Circumferential strain, %
Basal segments
Anterior	−24.2 ± 7.7	−25.1 ± 4.8	0.411
Anteroseptal	−23.2 ± 5.8	−16.7 ± 8.4	0.003
Inferoseptal	−22.1 ± 6.8	−24.8 ± 6.3	0.101
Inferior	−10.8 ± 5.2	−7.8 ± 6.8	0.014
Inferolateral	−20.4 ± 4.7	−21.2 ± 4.2	0.384
Anterolateral	−23.6 ± 5.8	−23.8 ± 2.9	0.733
All basal segments	−20.7 ± 2.9	−9.8 ± 1.6	0.159
Midventricular segments
Anterior	−20.6 ± 7.2	−20.1 ± 5.9	0.950
Anteroseptal	−26.6 ± 5.4	−23.5 ± 6.2	0.144
Inferoseptal	−24.6 ± 5.4	−23.5 ± 5.1	0.671
Inferior	−8.7 ± 5.4	−6.6 ± 4.3	0.139
Inferolateral	−22.1 ± 5.3	−22.3 ± 3.9	0.734
Anterolateral	−20.3 ± 5.4	−20.3 ± 5.4	0.906
All midventricular segments	−20.5 ± 3.5	−19.4 ± 1.8	0.101
Apical segments
Anterior	−19.3 ± 7.1	−18.7 ± 5.1	0.686
Septal	−30.4 ± 6.7	−30.9 ± 5.3	0.797
Inferior	−15.5 ± 7.2	−14.8 ± 5.5	0.587
Lateral	−24.6 ± 6.6	−26.1 ± 5.8	0.256
All apical segments	−22.4 ± 5.5	−22.6 ± 3.5	0.967
Longitudinal strain, %
Basal segments
Inferoseptal	−17.7 ± 8.1	−20.4 ± 9.8	0.407
Anterolateral	−21.2 ± 8.3	−20.7 ± 7.2	0.972
Midventricular segments
Inferoseptal	−13.7 ± 8.1	−16.6 ± 9.2	0.268
Anterolateral	−16.9 ± 7.9	−16.1 ± 6.1	0.901
Apical segments
Septal	−17.4 ± 8.1	−17.6 ± 4.8	0.873
Lateral	−12.7 ± 5.5	−14.8 ± 6.2	0.228
Apex	−2.79 ± 7.8	−3.31 ± 7.1	0.895
Note. Quantitative data are presented as M ± SD, where M is the mean value and SD is the standard deviation.

 

There was a general trend indicating that the absolute values of segmental circumferential strain in group 2 were higher than in group 1 (Fig. 1). However, circumferential myocardial strain in the basal inferolateral LV segment demonstrated an opposite pattern. With respect to segmental longitudinal strain, no consistent intergroup pattern was observed (Fig. 2).

 

Fig. 1. Circumferential strain of the left and right ventricles.

 

Fig. 2. Longitudinal strain of the left and right ventricles.

 

DISCUSSION

Summary of Primary Results

Patients with RV EDV ≥ 150 mL/m² exhibited higher RV ESV and more pronounced alterations in LV circumferential strain, which may be considered an additional criterion when making decisions regarding pulmonary valve replacement. These findings emphasize the clinical relevance of a comprehensive assessment of both volumetric and deformation cardiac parameters for diagnostic purposes and optimal treatment selection.

Discussion of Primary Results

Kempny et al. [23] used MRI with myocardial strain analysis to assess biventricular function in 28 patients after surgical repair of tetralogy of Fallot (mean age, 40.4 ± 13.3 years) compared with 25 healthy controls. The obtained strain values were compared with results from speckle-tracking echocardiography and simple endocardial border delineation. The authors demonstrated a statistically significant direct relationship between global strain parameters of the RV and LV.

Contemporary studies confirm that strain analysis enables detection of early myocardial injury before a reduction in ejection fraction becomes apparent [24, 25]. Furthermore, the clinical applicability of MRI-based feature-tracking (strain)¹ has been demonstrated in various cardiovascular diseases [26–28]. LV myocardial strain assessment using this method has been shown to be a sensitive predictor of subclinical dysfunction [29, 30].

Myocardial strain parameters are influenced by both sex and age; however, circumferential and longitudinal strain values from −17% to −20% and radial strain values greater than 25%–30% are generally considered to be within the normal range [31]. In patients with repaired tetralogy of Fallot, improvements in global LV circumferential and longitudinal strain were reported 6 months after transcatheter pulmonary valve implantation [32]. Moreover, global RV longitudinal strain has demonstrated associations with clinically relevant parameters, including exercise tolerance and oxygen consumption [23]. These findings were further supported in a large prospective study including 372 patients with repaired tetralogy of Fallot, in which LV global circumferential strain and RV global longitudinal strain independently predicted death, sudden cardiac death, or documented ventricular tachycardia [33, 34]. Furthermore, Moon et al. [35], in a case–control study (n = 16), demonstrated that longitudinal strain of both the RV and LV, as well as circumferential strain, were predictors of ventricular tachycardia and sudden cardiac death. Similar results were obtained in 15 patients after palliative Fontan procedures: global circumferential and longitudinal strain parameters of the single ventricle correlated with NYHA functional class and peak oxygen consumption during cardiopulmonary exercise testing [36]. Pulmonary valve replacement contributes to improvement of myocardial function in patients with tetralogy of Fallot, particularly through a reduction in RV volumes [15]. However, there are data indicating that, despite functional improvement, RV strain parameters continue to deteriorate over time compared with patients who did not undergo pulmonary valve replacement [37].

In patients with tetralogy of Fallot who experienced adverse outcomes, values of all myocardial strain parameters were significantly lower than in patients without such outcomes, with impairment of longitudinal strain of both ventricles demonstrating the strongest association with adverse clinical events [35].

Myocardial strain parameters reflect the degree of deformation of the cardiac muscle during contraction and relaxation. They represent an important tool for detailed assessment of cardiac function, allowing detection of subclinical myocardial abnormalities that may remain undetected with standard evaluation of ejection fraction.

Two types of myocardial deformation are distinguished. Longitudinal strain (LS) reflects shortening of myocardial fibers along the long axis of the heart, from the base to the apex. In healthy myocardium, global longitudinal strain has negative values, which are associated with physiological contraction and longitudinal shortening. Progressive longitudinal strain is an early marker of myocardial dysfunction and may be observed in cardiomyopathies and heart failure. Positive values are considered a sign of pathological changes (e.g., dilation). In patients with tetralogy of Fallot, increased RV load often leads to impairment of longitudinal RV function; therefore, longitudinal strain parameters may reflect the degree of adaptive myocardial remodeling. Circumferential strain (CS) characterizes myocardial shortening along the circumference of the heart. This parameter is key for assessing LV contractile function in the short-axis plane and is informative in the presence of hypertrophy, fibrosis, or other structural changes. Changes in circumferential strain may indicate compensatory hypertrophy under increased load. In patients with tetralogy of Fallot, this parameter serves as an indicator of RV remodeling due to afterload following surgical repair [24].

Myocardial strain parameters allow assessment of the functional state of not only the LV but also the RV, which is particularly important in patients with tetralogy of Fallot, who often require ongoing monitoring of RV function after defect repair [35].

The use of myocardial strain assessment enables identification of subclinical signs of dysfunction that may precede a decline in ejection fraction and other standard parameters. This makes the method particularly valuable for early diagnosis and timely planning of interventions [24]. For example, deterioration of RV longitudinal strain may be considered an early marker of developing right ventricular failure even before the onset of clinical symptoms [35].

In addition, assessment of strain parameters has practical value for determining indications for repeat surgical interventions, such as pulmonary valve replacement. Progressive worsening of strain parameters may be regarded as a predictor of the need for corrective intervention aimed at preventing further progression of heart failure [35].

Feature-tracking (strain) assessment ¹ has the potential to improve the accuracy of risk stratification and prediction of cardiovascular events in patients with systemic diseases, even before the development of clinically relevant cardiac dysfunction. This method is particularly valuable in cases in which myocardial dysfunction is subclinical and remains undetectable by conventional imaging techniques. It should be noted that patients with systemic diseases, unlike those with established cardiovascular disease, undergo regular cardiac imaging less frequently, whereas cardiac involvement in this population may lead to severe adverse outcomes. For this reason, the role of modern cardiac imaging techniques may be underestimated in this group of patients [38].

Study Limitations

When planning and conducting the study, the sample size required to achieve adequate statistical power was not calculated. Therefore, the obtained study sample cannot be considered sufficiently representative, which limits extrapolation of the results and their interpretation to the general population of similar patients outside the study.

The absence of a correlation between RV EDV values and RV strain parameters may be attributable to the limited number of observations analyzed. Further studies with larger patient cohorts are required.

CONCLUSION

Analysis of cardiac MRI data from 69 patients demonstrated statistically significant sex-related differences in RV EDV, as well as differences between patient groups with RV EDV values below and above 150 mL/m². In addition, patients with lower RV EDV had lower RV ESV, which may have clinical relevance for the assessment of RV function.

In the present study, statistically significant changes in myocardial strain parameters were identified in children after repair of tetralogy of Fallot depending on RV EDV value. In particular, statistically significant differences in circumferential strain of the basal LV segments indicate the effect of RV dilation on LV contractile function. The obtained results emphasize the diagnostic value of strain parameters and their potential role as an additional criterion when assessing indications for pulmonary valve replacement. Thus, incorporation of MRI-based myocardial strain analysis into clinical practice may improve decision-making accuracy and optimize management strategies in patients after radical repair of tetralogy of Fallot.

ADDITIONAL INFORMATION

Author contributions: A.M. Kabdullina, R.I. Rakhimzhanova, T.B. Dautov, Zh.S. Abdrakhmanova: conceptualization, methodology; A.M. Kabdullina: formal analysis, data curation, visualization, writing—original draft; A.B. Saduakassova: investigation, formal analysis; V.E. Sinitsyn: writing—review & editing. All the authors approved the final version of the manuscript for publication and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Acknowledgments: The authors express their gratitude to Professor Yuriy V. Pya, Dr. Sci. (Medicine), Head of the National Research Cardiac Surgery Center, for providing the opportunity to carry out this work.

Ethics approval: The study was approved by the Ethics Committee of the National Research Cardiac Surgery Center (approval No. 01-92/2021 dated April 22, 2021). All patients and their legal representatives provided written informed consent prior to participation in the study.

Funding sources: No funding.

Disclosure of interests: The authors have no relationships, activities, or interests for the last three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: No previously published material was used in this study or article.

Data availability statement: The editorial policy regarding data sharing does not apply to this work.

Generative AI: No generative artificial intelligence technologies were used to prepare this article.

Provenance and peer-review: This article was submitted unsolicited and reviewed following the standard procedure. The peer review process involved one external reviewer, two members of the Editorial Board, and the in-house science editor.

 

¹ Feature-tracking (strain) is a method for myocardial deformation analysis using standard cardiac magnetic resonance imaging data.

About the authors

Azhar M. Kabdullina

Astana Medical University

Author for correspondence.
Email: azharazh@mail.ru
ORCID iD: 0000-0003-0521-5484
SPIN-code: 4169-1761

MD

Kazakhstan, Astana

Valentin E. Sinitsyn

Lomonosov Moscow State University

Email: vsini@mail.ru
ORCID iD: 0000-0002-5649-2193
SPIN-code: 8449-6590

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

Raushan I. Rakhimzhanova

Astana Medical University

Email: rakhimzhanova01@rambler.ru
ORCID iD: 0000-0002-3490-6324

MD, Dr. Sci. (Med.), Professor

Kazakhstan, Astana

Tairkhan B. Dautov

University Medical Center

Email: tairkhan.dautov@mail.ru
ORCID iD: 0000-0002-5267-0108
SPIN-code: 8632-6605

MD, Dr. Sci. (Medicine), Professor

Kazakhstan, Astana

Zhanar S. Abdrakhmanova

Astana Medical University

Email: zhanna-ayan74@mail.ru
ORCID iD: 0000-0002-1890-0862

MD, Dr. Sci. (Medicine), Professor

Kazakhstan, Astana

Aigul B. Saduakassova

Medical Center Hospital of the President’s Affairs Administration of the Republic of Kazakhstan

Email: sadik.a@mail.ru
ORCID iD: 0000-0001-7089-5696

MD, Dr. Sci. (Medicine)

Kazakhstan, Astana

References

Supplementary files