Pectus excavatum (PE) is the most common congenital chest wall deformity with an estimated prevalence of 1 in 300–1000 live births. It is characterized by variable depression of the sternum and lower costal cartilages.
Several investigations support a cardiopulmonary impairment resulting from the anterior chest wall deformity in both adults and children. Great majority of studies reported a reduction in pulmonary functional indices, incomplete diastolic filling and decreased ejection fraction, stroke volume (SV), and cardiac output (CO).
However, the effects of PE on ventricular-arterial coupling (VAC), that is defined as the ratio of arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), and that represents the interplay between cardiac function and arterial system, have been poorly investigated in infants. To date, only two studies examined the interactions between the heart and the arterial system in infants and children with PE. These studies reported that myocardial contractility and afterload were impaired in children with PE and that both Ea and Ees were affected by body surface area (BSA) and not by pectus deformity.
We have recently demonstrated that chest shape, as noninvasively assessed by the modified Haller index (MHI), may affect VAC parameters in healthy pregnant women in the absence of reduced left ventricular contractility.
No previous study evaluated the correlation of MHI with Ea, Ees, and VAC in infants with PE. We hypothesized that, in infants with concave-shaped chest wall and/or PE, both Ea and Ees could be primarily altered by a narrow antero-posterior (A-P) thoracic diameter, rather than BSA, in the absence of any impairment in myocardial contractility. This hypothesis is derived from the assumption that all PE infants have a reduced A-P chest diameter, but not all PE infants should necessarily have a reduced BSA.
Accordingly, the present study was designed to investigate the influence of severity of chest shape alterations, as assessed by MHI, on VAC parameters in a consecutive group of PE infants at term.
Sixteen consecutive PE infants and 44 healthy infants with normal thoracic shape (controls) were analyzed between October 2018 and July 2021. The two groups of infants were selected from the Department of Neonatology of our institution through the MHI method, by using a cutoff value of 2.5, according to the PE definition based on a Haller index value >2.5. Notably, all consecutive infants with concave-shaped chest wall and/or PE (MHI >2.5) and those with normal chest shape conformation (MHI ≤2.5) were entered into this study.
Exclusion criteria were the following: prematurity, patent ductus arteriosus and other congenital heart diseases, respiratory distress syndrome, infections, perinatal asphyxia, hemodynamic instability, poor or inadequate acoustic windows, and parental refusal to provide informed consent.
Following infants’ data were collected: birth length and weight, BSA, body mass index (BMI), heart rate, and blood pressure values at birth.
Each infant underwent a general examination with weight and nutritional status assessment, an instantaneous blood pressure measurement, a 12-lead electrocardiogram, a two-dimensional (2D) transthoracic echocardiography (TTE), and finally MHI assessment. All infants were examined within the 3rd day of life.
All procedures were in accordance with the ethical standards of our Institutional Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from parents of each infant included in the study, and the protocol was approved by the Local Ethics Committee (Committee's reference number CE-78.2021).
Conventional echo-Doppler examination
All echocardiograms were performed by the same cardiologist using a commercially available Philips Sparq ultrasound machine (Philips, Andover, Massachusetts, USA) with a 7.5 MHz transducer. All parameters were measured according to the recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
The following conventional echo-Doppler parameters were recorded: interventricular septum thickness, posterior wall (PW) thickness, and left ventricular end-diastolic diameter (LVEDD) from the parasternal long-axis view; relative wall thickness (RWT) assessed by the formula RWT = 2PW/LVEDD; left ventricular mass index calculated by the Devereux's formula; left atrial diameters and left atrial end-systolic volume index; left ventricular end-diastolic volume index, left ventricular end-systolic volume index (LVESVi), and left ventricular ejection fraction estimated with the biplane modified Simpson's method; mitral annular plane systolic excursion; E/A ratio and average E/e’ ratio, as indices of left ventricular diastolic function; right ventricular inflow tract, tricuspid annular plane systolic excursion, and finally systolic pulmonary artery pressure (SPAP) derived by the modified Bernoulli formula; and finally, aortic root, ascending aorta, and aortic arch diameters measured by the “leading edge-to-leading edge” convention.
Ventricular-arterial coupling parameters
End-systolic pressure (ESP) was estimated as 0.9 × brachial systolic blood pressure. SV was obtained from the equation SV = LVOT area × LVOT-VTI, where LVOT represents the left ventricular outflow tract and VTI is the velocity time integral; CO was calculated by the formula CO = heart rate × SV.
Concerning VAC components, the effective Ea index (EaI) was calculated as the ratio of ESP to stroke volume index (SVi), whereas the Ees index (EesI) was measured as the ratio of ESP to LVESVi. The noninvasive assessment of VAC was derived from the Ea/Ees ratio.
Modified Haller index assessment
The MHI was obtained from the ratio of chest transverse diameter (assessed by a rigid ruler coupled to a level) over the distance between sternum and spine (assessed by 2D-TTE) [Figure 1].
The primary endpoint of the study was to investigate the influence of severity of chest shape alterations, as assessed by MHI, on VAC parameters (EaI, EesI, and Ea/Ees ratio) in term infants with PE (MHI >2.5) versus controls (MHI ≤2.5). The secondary endpoint of the study was to evaluate the influence of BSA on the same parameters in the two groups of infants.
For the two groups of infants, continuous data are expressed as mean ± standard deviation (SD), while categorical data are presented as number (percentage).
Student's t-test and Chi-square test were used to compare continuous and categorical variables, respectively, between PE infants and controls.
The correlation of MHI with VAC parameters and subsequently of BSA with the same parameters, performed for PE infants and controls separately, was evaluated by using the Pearson's correlation coefficient. Linear regression analysis was performed to estimate the effect of the main anthropometrics (MHI and BSA, respectively) on VAC parameters, in each group of infants.
Statistical power analysis was performed for this study. A sample size of 16 PE infants and 16 infants with normal chest shape reached 80% of statistical power to detect a 2.5 points difference in the investigated VAC parameters between the two groups with a SD of 2.5 for each parameter, using a two-sided equal-variance t-test with a significance level (alpha) of 5%.
Statistical analysis was carried out using the software SPSS, version 26 (SPSS Inc., Chicago, Illinois, USA), with P values below 0.05 deemed statistically significant.
The main demographic, anthropometric, and obstetric parameters detected in PE infants and controls in perinatal period are listed in Table 1.
Approximately two-third of PE infants (68.7%) were males. Compared to controls, PE infants were found with significantly lower length and weight percentiles (both P < 0.001), significantly smaller BSA (0.19 ± 0.02 m2 vs. 0.22 ± 0.02 m2, P < 0.001), and BMI (13.2 ± 1.1 kg/m2 vs. 14.1 ± 1.2 kg/m2, P = 0.01). However, not all PE infants had smaller BSA than controls; indeed, 10 (62.5%) of them had smaller BSA than controls, while the remaining 6 (37.5%) had a similar BSA to that of controls.
The average value of MHI in PE infants was 2.76 ± 0.2. Concerning MHI components, the A-P internal thoracic diameter was significantly shorter in PE infants than controls (3.6 ± 0.3 vs. 5.0 ± 0.4 cm, P < 0.001), whereas no statistically significant differences were found in the latero-lateral external thoracic diameter between the two groups of infants (9.9 ± 0.7 cm vs. 10.0 ± 1.2 cm, P = 0.75). All PE infants had a narrower A-P internal thoracic diameter than controls. No infant was found with severe PE (MHI >3.2).
Analysis of the remaining clinical parameters (Appearance, Pulse, Grimace, Activity, and Respiration score, heart rate, and blood pressure values) did not show any statistically significant difference between the two groups of infants.
On 2D-TTE, PE infants had a significantly smaller size of all cardiac chambers than controls. Analysis of left ventricular systolic and diastolic function, right ventricular longitudinal function, and pulmonary hemodynamics did not reveal any statistically significant difference between the two groups of infants. Finally, the aortic diameters were similar in the two groups of infants [Table 2].
Assessment of VAC parameters [Table 3] revealed that PE infants were diagnosed with significantly lower SVi (14.3 ± 2.5 ml/m2 vs. 18.1 ± 3.3 ml/m2, P < 0.001) and cardiac output index (2.1 ± 0.4 l/min/m2 vs. 2.8 ± 0.5 l/min/m2) and significantly smaller LVESVi (4.2 ± 0.9 ml/m2 vs. 5.4 ± 1.0 ml/m2, P < 0.001) than controls, with no difference in ESP between the two study groups (61.0 ± 3.0 mmHg vs. 59.2 ± 4.5 mmHg, P = 0.14). Concerning SV components, LVOT diameter was significantly shorter in PE infants than controls (3.1 ± 0.5 mm vs. 4.0 ± 0.6 mm, P < 0.001), whereas LVOT-VTI was similar in both the groups of infants (0.35 ± 0.08 cm vs. 0.34 ± 0.07 cm, P = 0.64).
Both EaI (4.4 ± 1.0 mmHg/ml/m2 vs. 3.4 ± 0.6 mmHg/ml/m2, P < 0.001) and EesI (15.1 ± 3.0 mmHg/ml/m2 vs. 12.7 ± 2.5 mmHg/ml/m2, P = 0.003) were significantly increased in PE infants than controls. The resultant VAC (0.30 ± 0.10 vs. 0.30 ± 0.08, P > 0.99) was similar in both the groups of infants.
Linear regression analysis showed that, in infants without anterior chest wall deformity (MHI ≤2.5), all VAC parameters were independent of MHI; conversely, in infants with PE (MHI >2.5), both EaI (r = 0.93) and EesI (r = 0.87) were linearly correlated with MHI (both P < 0.001), indicating that the worse was the anatomical deformity of the chest, the greater were EaI and EesI. On the other hand, no correlation was found between MHI and VAC in PE infants (r = 0.02) [Figure 2].
Finally, in infants with MHI ≤2.5, all VAC parameters were independent of BSA, whereas in PE infants (MHI >2.5), a moderate inverse correlation between BSA and both EaI (r = −0.50) and EesI (r = −0.55) was detected. However, no correlation was observed between BSA and VAC in PE infants (r = 0.05) [Figure 3].
This prospective case–control study described the main anthropometric, echocardiographic, and hemodynamic characteristics of a consecutive population of PE infants compared to a control group of infants without anterior chest wall deformity. PE infants (MHI >2.5) were predominantly males, with a narrow A-P chest diameter, small size of all cardiac chambers, normal systo-diastolic function, and normal pulmonary hemodynamics. Due to a concomitant reduction in SV index and left ventricular end-systolic dimensions, in the presence of similar ESP, both EaI and EesI were significantly increased in PE infants than controls. The resultant VAC (Ea/Ees ratio) did not differ between the two study groups.
A strong linear correlation between MHI and both arterial EaI and EesI was demonstrated in PE infants, but not in controls. This correlation was stronger than that observed between BSA and the same parameters in PE infants. Finally, nor MHI neither BSA showed any correlation with VAC in both the groups of infants.
As far as we know, this is the first study that evaluated the influence of chest shape on VAC parameters in PE infants at term during perinatal period.
Originally, PE infants were selected by employing the MHI, a noninvasive index of chest wall conformation, that yields the values of chest shape comparable to those obtainable through chest X-rays, without exposing the subject to radiations.
MHI has been developed in our echo laboratory and has been validated in 2018 through a comparative study of transthoracic ultrasound and chest X-ray. However, no infant was included in the validation study. The MHI method allows to differentiate those individuals with concave-shaped chest wall (due to a narrow A-P chest diameter) from those without anterior chest wall deformity. This noninvasive method is particularly useful for assessing the possible influence of chest shape on cardiac kinetics and systodiastolic function in various clinical contexts.
To date, there are a few number of studies that examined the influence of anthropometrics on VAC parameters in normal children.
Khosroshahi et al. reported that both EaI and EesI were inversely correlated with BSA, where the higher values of EaI and EesI were detected in children with BSA of <0.4 m2, whereas the VAC remained unchanged in normal children with different age groups and different BSA. Consistent with the assumption of Khosroshahi et al., our results confirmed a moderate inverse correlation between the BSA and VAC parameters in PE infants. However, the MHI method highlighted a stronger correlation of degree of infant's chest deformity with EaI and EesI. The greater was the MHI, the greater were both the EaI and the EesI obtained in PE infants. The main explanation for our findings is related to the leading role exerted by a narrow A-P internal thoracic diameter in decreasing cardiac chamber size in PE infants. The short A-P chest diameter was responsible for reduction of both LVOT diameter (and consequently SV) and LVESV which are the main components of Ea and Ees calculation, respectively. On the other hand, not all PE infants were found with a smaller BSA than controls; for this reason, the correlation between BSA and VAC parameters was weaker than that observed between MHI and both EaI and EesI.
Our results are in disagreement with Akyüz Özkan et al. which did not find any differences between children with PE and controls with regard to EaI and EesI, and stated that a possible reason for this was that both EaI and EesI were affected by BSA and not by pectus deformity; moreover, the author reported that the myocardial contractility and afterload were impaired in children with PE. Differently from the authors, our results revealed that biventricular systolic function, left ventricular filling pressures, and other hemodynamic indices, such as LVOT-VTI, SPAP, and VAC, were similar in both the groups of infants. The concomitant increase in EaI and EesI detected in PE infants contributed to maintain a VAC (Ea/Ees ratio) similar to that of infants without anterior chest wall deformity. Therefore, our findings excluded any intrinsic cardiovascular dysfunction in PE infants. Finally, the strong inverse correlation we found between MHI and both EaI and EesI in PE infants, confirmed the importance of chest wall conformation in influencing VAC parameters.
The main clinical implication of our findings is that impaired EaI and EesI may not always be related to myocardial dysfunction and that other factors unrelated to myocardial contractility, especially anatomical and/or extrinsic mechanical factors, may influence VAC parameters. A concave-shaped chest wall conformation (defined by an MHI >2.5), primarily related to a narrow A-P chest diameter, should be considered a relevant factor that could affect VAC parameters. This assumption is appropriate both for infants and adults.
We suggest to correlate hemodynamical and functional cardiac variables not only to BSA but also to chest shape, as noninvasively assessed by MHI, in term infants.
MHI assessment might reveal and explain physiologically different changes in VAC variables, primarily depending on the infant's chest shape conformation.
A number of limitations of the present study should be acknowledged. First, the sample size of PE infants enrolled was relatively small, due to the low number of infants with MHI >2.5 eligible for enrolment over a medium-term period. Second, infants with more advanced chest deformity (MHI >3.2) were not included in the study. Finally, the single-beat method was not employed for calculating EesI in the present study. However, the approximation proposed by Chantler et al. we used has been extensively applied for the examination of VAC parameters in different age groups.
PE strongly influences both Ea and Ees in term infants with PE, due to extrinsic thoracic compression on cardiac chambers, in the absence of any intrinsic cardiovascular dysfunction.
Biventricular systolic function, diastolic filling, and the resultant VAC (Ea/Ees ratio) are not impaired by the deformity of the anterior chest wall.
Noninvasive chest shape assessment should be implemented in the clinical practice, when evaluating VAC parameters in infants, especially in those with PE.
The study was approved by the institutional Ethics Committee (“Comitato Etico Indipendente IRCCS MultiMedica”). Committee's reference number: CE-78.2021.
This work has been supported by the Italian Ministry of Health Ricerca Corrente - IRCCS MultiMedica.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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