A CHD is the most common anomaly given by birth Reference Dolk, Loane and Garne1 with a prevalence of 7.32 per 1000 births in Europe. Infants are more likely to grow up and reach adolescence and adulthood. Reference Avila, Mercier and Dore2 Medical care, especially in a specialised tertiary care centre becomes more important. However, “late” on-set comorbidities such as liver diseases in Fontan patients, cancer, or a decrease in exercise capacity occur more often than in the normal population. Reference Hock, Schwall and Pujol3–Reference Tutarel, Kempny and Alonso-Gonzalez5 Already in childhood, low exercise capacity, Reference Hock, Häcker and Reiner6–Reference Müller, Christov, Schreiber, Hess and Hager9 a higher risk of impaired functional outcomes such as motor competence – not only fine and gross motoric but also strength, Reference Holm, Fredriksen, Fosdahl, Olstad and Vøllestad10,Reference Bolduc, Dionne, Gagnon, Rennick, Majnemer and Brossard-Racine11 – or subsequent medical issues are frequent. Reference Massin, Astadicko and Dessy12,Reference Neidenbach, Lummert and Vigl13
The heart can particularly affect lung volumes and their function due to the common limited space in the thoracic cage. Second, lung development may already be affected by abnormal blood flow during embryonic development, Reference Guo, Liu, Gu, Zhang, Sun and He14,Reference Hislop15 especially if the pulmonary blood flow is affected (for example, in the absence of a pulmonary valve or severe stenosis, or on the other side severe recirculation in a large septum defect). Third, consecutive palliative surgeries (like staged palliation of univentricular hearts) can influence thoracic compliance and growth, cause pleural adhesions, and alter lung function. Reference Kanakis, Martens, Kostolny, Petsios, Giannopoulos and Muthialu16,Reference Ohuchi, Ohashi, Takasugi, Yamada, Yagihara and Echigo17 Müller et al. have shown that lung volumes correlate with the number of thoracotomies. Reference Müller, Ewert and Hager18 However, comprehensive knowledge of lung function in CHD is still lacking. Former studies concentrated on the late effects of surgery. Reference Müller, Ewert and Hager18,Reference Healy, Hanna and Zinman19 Therefore, the present systematic review aims to investigate (me) the state of the literature in the context of lung function testing in CHD within the last decade as well as (II) its quality and methodology and consequences for future studies.
Material and Method
Objective
This study investigates lung function parameters in patients with a congenital heart defect to figure out whether abnormalities are more likely, common, or rare. Furthermore, highlighting patients under risk is elaborated and examination strategies are provided.
Searching strategy
The review was performed systematically. Relevant databases were chosen: PubMed, Cochrane, and Scopus. We only included studies published in English with full-text available. Final data research update was performed in July 2021. A standardised protocol was used for population, intervention, comparison, outcome, method (PICO-C), Reference Uman20 and applied as follows:
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“Congenital heart defect” OR “Congenital heart disease” OR “Congenital heart defects” OR “Congenital heart diseases” OR “Fallot” OR “Ebstein” OR “Eisenmenger” OR “Transposition of the great arteries” OR “Fontan” OR “Cavopulmonary” OR “Cavo-Pulmonary” OR “septal defect”AND
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“lung function” OR “lung volume” OR “Spirometry” OR “Bodyplethysmography” OR “lung capacity” OR “body box” OR “pulmonary function” OR “Body plethysmography”.
Furthermore, only studies from January 2010 to December 2020 (the last decade) were analysed.
Data collection
Data from children, adolescents, and adults with CHD were included in the review. All relevant studies were screened for eligibility with title and abstract. Inclusion criteria consisted of CHD patients as subjects and lung volumes (e.g. forced vital capacity). Lung volumes must have been measured standardised and this also had to be noted in the manuscript. Furthermore, literature for the reference values had to be reported. Both % of predicted values and z-score were considered.
Two reviewers conducted a full-text analysis. If at least one of them considered the published study as eligible, the study was included in the review.
Rating of the studies
Studies, which were included in the review, were rated by The National Heart, Lung, and Blood Institute “Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies”. The rating consists of “yes”, “no”, and “other” (e.g. cannot determine). Following their guidelines, the rating of the studies depends on their individual “risk of bias”. Therefore, if the two reviewers concluded that a study has a (high) risk of bias, it was rated lower than studies with no or low risk of bias. There is no strict guideline for the number of “yes” leading to a better conclusion. Studies with another design than cohort or cross-sectional (e.g. Fritz et al. Reference Fritz, Müller, Oberhoffer, Ewert and Hager21 ) were excluded due to their character of inclusion and exclusion criteria leading to a risk of bias in subjects’ lung function. Only one intervention study Reference Hedlund, Ljungberg, Söderström, Lundell and Sjöberg22 was included since no exclusion criteria that may influence the outcome (lung function) were reported.
Results
Selected studies
Figure 1 shows the inclusion and exclusion process of the review. After full-text analyses (n = 52), 32 studies were excluded because no established reference was provided (e.g. only “[…] with <80% predicted […]”) or their origin for reference values was missed. Two studies were excluded since the sub-groups were not eligible (e.g. reduced lung volumes in CHD patients vs. normal results in CHD patients) and one further study due to its randomised controlled trial nature which has a risk of bias due to in- and exclusion criteria. Reference Fritz, Müller, Oberhoffer, Ewert and Hager21 However, the intervention study from Hedlund et al. Reference Hedlund, Ljungberg, Söderström, Lundell and Sjöberg22 was included since the inclusion criteria consisted of parameters that will not affect lung function in CHD patients (e.g. myocarditis or moved to another geographical region). Only baseline characteristics were used for analyses.
Fig. 1 Study concept and exclusion criteria.
Study quality
All studies stated that they performed a standardised lung function test, which guarantees comparability between results. Classification of CHD was well described and results were given precisely in almost all studies. Only Abassi et al. Reference Abassi, Gavotto and Picot23 used an uncommon classification of CHD. All studies investigated at least spirometry parameters (forced vital capacity and forced expiratory volume in 1 s, FEV1). Only six studies investigated total lung capacity or residual volume by body plethysmography and diffusion capacity measurement. Reference Hedlund, Ljungberg, Söderström, Lundell and Sjöberg22,Reference Fabi, Balducci and Cazzato24–Reference Turquetto, Canêo and Agostinho28 The number of individuals studied ranged from 17 Reference Guenette, Ramsook and Dhillon25 to 168 Reference Fabi, Balducci and Cazzato24 and includes 380 body plethysmography tests as well as 4131 spirometry tests.
Study quality ratings
The quality of studies in this NHLBI tool does not depend on the total score as it is in others. Reference Pieper, Waltering, Holstiege and Büchter29 Each study is rated individually. If in one study the independent reviewers were not in agreement with the quality range, they discussed the risk of bias due to missing or insufficient provided information in the study. The lower the risk, the higher the rating.
Table 1 shows the result of the NHLBI study rating. All studies provided a research question and defined a study population (Q1 and Q2). The study population (Q3 and Q4) is often sufficiently described, but more often it was not determined. A selection bias in subjects must be assumed in these studies. No study included a justification of sample size which may be the nature of limited subjects due to this special cohort and second due to the character of cross-over studies (Q5). However, also in these cohorts, a power-analyses should be done in advance. Some questions can only be answered with “not applicable” (e.g. Q 10) due to the nature of the CHD: patients are born with this condition and therefore the exposure measurement cannot be “repeated”. Another risk is the lack of blinding of studies, which no study fulfilled (Q12). However, in each patient group, it was already clear that all of them suffer from a CHD since they visit a specialised clinic (Q8–Q10).
Table 1. Quality assessment according to the NHLBI quality assessment tool for observational cohort and cross-sectional studies.
** study double since both, Fontan and TOF patients were investigated; ¥ for this study no mean ± SD was given.
Abbreviations: NHLBI: The National Heart, Lung, and Blood Institute, Q: question, CSS: cross-sectional study, CS: cohort study, IS: Intervention Study.
Question 1. Research question, Questions 2 and 3. Study population, Question 4. Groups recruited from the same population and uniform eligibility criteria, Question 5. Sample size justification, Question 6. Exposure assessed prior to outcome measurement, Question 7. Sufficient timeframe to see an effect, Question 8. Different levels of the exposure of interest, Question 9. Exposure measures and assessment, Question 10. Repeated exposure assessment, Question 11. Outcome measures, Question 12. Blinding of outcome assessors, Question 13. Follow-up rate, Question 14. Statistical analyses.
“√” fulfilled, “–“ not fulfilled, CD: cannot determine, NA: not applicable.
Four studies were rated as good Reference Hedlund, Ljungberg, Söderström, Lundell and Sjöberg22,Reference Abassi, Gavotto and Picot23,Reference Opotowsky, Landzberg and Earing30,Reference Cohen, Buelow and Dixon31 indicating a low risk of bias. Nine studies Reference Fabi, Balducci and Cazzato24,Reference Turquetto, Canêo and Agostinho28,Reference Shafer, Opotowsky and Rhodes32–Reference Morales Mestre, Reychler, Goubau and Moniotte38 were considered “fair” with a lower internal validity in the view of the reviewers. The other studies Reference Guenette, Ramsook and Dhillon25–Reference Liptzin, Di Maria and Younoszai27,Reference Ginde, Bartz and Hill39 showed a higher risk of bias (e.g. missing a control group from a similar population) and further weaknesses also compared to the other studies.
Study characteristics
Seven studies Reference Hedlund, Ljungberg, Söderström, Lundell and Sjöberg22,Reference Guenette, Ramsook and Dhillon25–Reference Turquetto, Canêo and Agostinho28,Reference Opotowsky, Landzberg and Earing30,Reference Shafer, Opotowsky and Rhodes32,Reference Callegari, Neidenbach and Milanesi33 investigated patients with Fontan palliation (or children after total cavopulmonary connection, TCPC) including 704 patients (306 female). Four studies Reference Cohen, Buelow and Dixon31,Reference Shafer, Opotowsky and Rhodes32,Reference Demirpençe, Güven and Yılmazer34,Reference Powell, Mays, Knecht and Chin35 included patients after repaired tetralogy of Fallot. These studies examined 219 patients (103 female). Further six studies Reference Abassi, Gavotto and Picot23,Reference Fabi, Balducci and Cazzato24,Reference Alonso-Gonzalez, Borgia and Diller36–Reference Ginde, Bartz and Hill39 included 3,208 children and adults with various CHDs (1324 female).
Overall, 14 studies Reference Abassi, Gavotto and Picot23–Reference Turquetto, Canêo and Agostinho28,Reference Opotowsky, Landzberg and Earing30,Reference Cohen, Buelow and Dixon31,Reference Callegari, Neidenbach and Milanesi33–Reference Powell, Mays, Knecht and Chin35,Reference Hawkins, Taylor, Sillau, Mitchell and Rausch37–Reference Ginde, Bartz and Hill39 were cross-sectional studies, two cohort studies Reference Shafer, Opotowsky and Rhodes32,Reference Alonso-Gonzalez, Borgia and Diller36 and one intervention study. Reference Hedlund, Ljungberg, Söderström, Lundell and Sjöberg22 All studies refer to a local/national or worldwide reference, 7 of the 14 cross-sectional studies compared results with age and gender-matched healthy reference cohorts. Reference Abassi, Gavotto and Picot23–Reference Guenette, Ramsook and Dhillon25,Reference Turquetto, Canêo and Agostinho28,Reference Demirpençe, Güven and Yılmazer34,Reference Powell, Mays, Knecht and Chin35,Reference Hawkins, Taylor, Sillau, Mitchell and Rausch37 The other studies used healthy reference cohorts only. The two cohort studies used either norm references Reference Alonso-Gonzalez, Borgia and Diller36 or an age-matched reference cohort with CHD. Reference Shafer, Opotowsky and Rhodes32 Hedlund et al. Reference Hedlund, Ljungberg, Söderström, Lundell and Sjöberg22 included a matched cohort in their 12-week intervention study. Table 2 provides more detailed information on all studies.
Table 2. Study characteristics and outcomes.
** study double since both, Fontan and TOF patients were investigated; ¥ for this study no mean ± SD was given
Abbreviations : ANOVA: analyses of variance, AS: aortic stenosis, ASD: atrial septal defect, AV: volume of the alveolar, ccTGA: congenital corrected transposition of the great arteries, CHD: congenital heart disease, CG: control group, CoA: coarctation of the aorta, DLCO: transfer factor of the lung for carbon monoxide (diffusion capacity), ERV: expiratory reserve volume, FEF: forced expiratory flow, FEV1: forced expiratory volume in 1 s, FRC: functional residual capacity, FVC: forced vital capacity, IC: inspiratory capacity, IQR: interquartile range, LLN: lower limit if normal, n: number of subjects, MIP: maximum inspiratory pressure, N/A: not applicable (data not given in results), NHANES: National Health and Nutrition Examination Survey, (p)AVSD: (partial) atrioventricular septal defect, PA-iVS: pulmonary atresia with intact ventricular septum, PEF: peak expiratory flow, PS: pulmonary stenosis, RV: residual volume, SD: standard deviation, SNIP: sniff nasal inspiratory pressure, TCPC: total cavopulmonary connection, TGA: transposition of the great arteries, TLC: total lung capacity, TOF: tetralogy of Fallot, UVH: univentricular heart, VC: vital capacity, VSD: ventricular septal defect.
Lung function tests and reference norms
All selected studies refer to cohort studies investigating healthy subjects. It is striking that there is hardly any agreement between the studies concerning the norm values: Abassi et al., Reference Abassi, Gavotto and Picot23 as well as Morales Mestre et al., Reference Morales Mestre, Reychler, Goubau and Moniotte38 used the current 2012 GLI references from the Global Lung Initiative published by Quanjer et al. Reference Quanjer, Stanojevic and Cole40 Two studies referred to Brusasco et al., Reference Brusasco41 and a further five to Pellegrino et al. Reference Pellegrino42 The other studies used local or national studies as references, Reference Demirpençe, Güven and Yılmazer34,Reference Tan, Bourbeau and Hernandez43–Reference Hedenstrom, Malmberg and Fridriksson45 comparatively old references, Reference Quanjer, Borsboom and Brunekreef46–Reference Goldman and Becklake50 or other references. Reference Stanojevic, Wade and Stocks51 Therefore, statistical analysis with an, e.g., meta-analysis is not practicable. Furthermore, since the results are mainly in common (Fig 2) between the studies, there was no benefit in calculating effect size.
Fig. 2 Forrest plots in FVC, FEV1, and its ratio.
* no SD given, ° no data available, ** study double since both, Fontan and TOF patients were investigated. Abbreviations: FVC: forced vital capacity, FEV1: forced expiratory volume in 1 seconds, TOF: Tetralogy of Fallot, CHD: congenital heart disease, ASD: atrial septal defect, VSD: ventricular septal defect, (p)AVSD: (partial) atrioventricular septal defect, CoA: coarctation of the Aorta, AS: aortic stenosis, TGA: transposition of the great arteries, ccTGA: congenitally corrected transposition of the great arteries.
Discussion
Despite the heterogeneous quality of the studies and the use of different reference values in the studies, Fontan and tetralogy of Fallot patients, as well as cohorts of mixed CHDs, showed mainly a reduced forced vital capacity with about 50% of patients in the striking result range.
Lung volumes in CHD patients
Studies on Fontan patients
Seven studies investigated patients with Fontan palliation or total cavopulmonary connection, the “modern“ palliation. Reference Hedlund, Ljungberg, Söderström, Lundell and Sjöberg22,Reference Guenette, Ramsook and Dhillon25–Reference Turquetto, Canêo and Agostinho28,Reference Opotowsky, Landzberg and Earing30,Reference Shafer, Opotowsky and Rhodes32,Reference Callegari, Neidenbach and Milanesi33 Hedlund et al. performed an intervention study, Shafer et al. a cohort studies, and the remaining a cross-sectional studies. All studies showed mild to significant limitations in terms of lung volumes in children and adolescents with CHD. Opotowsky et al. Reference Opotowsky, Landzberg and Earing30 highlight that almost half of 260 included patients were below the lower limit of normal in forced vital capacity (represented in 80% of predicted with their reference).
Remarkable is that studies that included children Reference Hedlund, Ljungberg, Söderström, Lundell and Sjöberg22,Reference Idorn, Hanel and Jensen26,Reference Turquetto, Canêo and Agostinho28 show much higher and more likely normal volumes in forced vital capacity and FEV1 (≥80% of predicted). These studies on children include patients with the nowadays common surgical repair which probably leads to better functional outcomes. Reference Hock, Reiner and Neidenbach8 However, results are significantly lower compared to healthy peers.
Studies investigating adults Reference Guenette, Ramsook and Dhillon25,Reference Shafer, Opotowsky and Rhodes32,Reference Callegari, Neidenbach and Milanesi33 show significantly lower results in lung volumes (∼60–75% of predicted). It may be concluded that the current surgical procedure “protects” children’s lung function – or that nowadays patients are more likely to perform sports and exercise, and therefore, their lung volumes may be less affected and more likely in a normal range. Daily exercise and sports lead to better exercise capacity Reference Gomes-Neto, Saquetto and da Silva e Silva52,Reference Hansen and Tierney53 which vice versa correlates with lung volumes and function. Reference Hedlund, Ljungberg, Söderström, Lundell and Sjöberg22,Reference Abassi, Gavotto and Picot23,Reference Turquetto, Canêo and Agostinho28,Reference Gomes-Neto, Saquetto and da Silva e Silva52,Reference Hock, Remmele, Oberhoffer, Ewert and Hager54
Moreover, Guenette et al. Reference Guenette, Ramsook and Dhillon25 showed that total lung capacity and diffusion capacity is lower in their Fontan cohort. Low total lung capacity represents a small lung. Additionally, lungs may be affected in diffusion by the passive circulation after the Fontan procedure, presented in diffusion capacity. Unfortunately, in this study, no data on diffusion capacity/VA were reported. Further studies are needed with much larger sample sizes (in this study only 17 patients were included) to re-evaluate these findings.
All included studies demonstrate lower values than the reference (<80% of predicted or < −1.645 in z-score) or even impairments in FVC and FEV1. Almost no patient showed obstructive patterns [27]. Strikingly, some studies show that body plethysmography (TLC and RV) is normal, with only 165 Fontan patients underwent this test. Reference Idorn, Hanel and Jensen26–Reference Turquetto, Canêo and Agostinho28
Studies on TOF patients
Four studies Reference Cohen, Buelow and Dixon31,Reference Shafer, Opotowsky and Rhodes32,Reference Demirpençe, Güven and Yılmazer34,Reference Powell, Mays, Knecht and Chin35 examined a total of 219 patients with repaired tetralogy of Fallot. Shafer et al. conducted a cohort study and the other three cross-sectional studies. As in Fontan patients, also in this cohort, children show better results compared to adults. Demirpençe et al. and Powell et al. show only a slight decrease in forced vital capacity and FEV1 in their investigated children with results below 80% of predicted. Cohen et al. studied 122 adult patients with tetralogy of Fallot and their results show mild impairments in 19% and moderately to severe impairments in further 19% of the patients. Also, Shafer et al. provide impaired results in tetralogy of Fallot patients with forced vital capacity in % of predicted 62.8 ± 16.7 and FEV1: 59.0 ± 15.3. It seems, that again, children who undergo surgical repair “today” benefit from improvements in surgical intervention regarding the results in lung volumes. Future studies should evaluate this hypothesis – it is questionable, if the lung function parameters are better or if they decrease later on – or if for example daily activity and sports play a role. Reference Akam-Venkata, Sriram, French, Smith and Aggarwal55
None of the reviewed studies performed body plethysmography in tetralogy of Fallot patients. It is advisable to test those with a restrictive pattern (forced vital capacity <80% of predicted) regarding their total lung capacity to eliminate the risk of hyperinflation (normal total lung capacity while forced vital capacity is reduced leading to a high residual volume). Reference D'Ascanio, Viccaro and Calabrò56
Studies with all CHD patients
The last six studies, Reference Abassi, Gavotto and Picot23,Reference Fabi, Balducci and Cazzato24,Reference Alonso-Gonzalez, Borgia and Diller36–Reference Ginde, Bartz and Hill39 that are included in this review, deal with various kinds of CHD. Mainly, the heart defects were separated following different possibilities: e.g. left heart lesion (as aortic stenosis), right heart lesion (as tetralogy of Fallot), and other lesions (as transposition of the great arteries), Reference Hawkins, Taylor, Sillau, Mitchell and Rausch37 data were presented for each CHD separately, Reference Abassi, Gavotto and Picot23,Reference Ginde, Bartz and Hill39 or other different groupings were made. Reference Abassi, Gavotto and Picot23,Reference Fabi, Balducci and Cazzato24,Reference Alonso-Gonzalez, Borgia and Diller36,Reference Morales Mestre, Reychler, Goubau and Moniotte38
However, the main results are similar compared to those with Fontan or tetralogy of Fallot patients: while children Reference Abassi, Gavotto and Picot23,Reference Fabi, Balducci and Cazzato24,Reference Morales Mestre, Reychler, Goubau and Moniotte38 have fairly normal lung volumes, adults more often show reduced or impaired results. Reference Alonso-Gonzalez, Borgia and Diller36,Reference Ginde, Bartz and Hill39 The study by Hawkins et al. included both age groups and found decreased lung volume results in 20% of all their subjects. Reference Hawkins, Taylor, Sillau, Mitchell and Rausch37 Anatomical basics, heart surgery, and the number of surgeries can favour these decreased lung volumes. Reference Alonso-Gonzalez, Borgia and Diller36,Reference Hawkins, Taylor, Sillau, Mitchell and Rausch37 Again, no study investigated total lung capacity or RV in the patients. Overall, the results show that approximately half of all investigated patients have a restrictive pattern in spirometry.
Figure 2 summarises the main results of all studies, separated in CHD. It has to be mentioned that in this figure, the studies from Liptzin et al, Cohen et al., and Hawkings et al. are not presented. None of these studies reported mean or medians as results, only the numbers of impaired results were given.
Clinical impact
The studies in this review show that about half of all investigated patients have fairly normal or only mild restrictive patterns occur (Table 2, Fig 2). Lung physiology in patients with CHD can be affected by several factors. Due to decreased blood flow antenatal, as neonates and infants, Reference Guo, Liu, Gu, Zhang, Sun and He14,Reference Hislop15 maldevelopment of the lungs may result in possible reductions in lung volumes. Reference Healy, Hanna and Zinman19
Surgical palliation or repair already takes place in early childhood. Reference Kaza and Gruber57 At this time, lung growth is not yet complete. Underlying restrictions may improve or even disappear with time. Therefore, lower restrictions compared to studies with adults are not surprising since they often underwent surgical interventions later in age compared to today – which has to be investigated in future studies. Surgical improvements during the last decades additionally enhanced children’s clinical situation. Future studies should evaluate, if these children can maintain their “good” and normal volumes or if there may be a point of change during their lifetime, as we know from exercise capacity, the natural decline with time increases during the decades. Reference Eshuis, Hock and Sarvaas58
Remarkably, all included studies report an increased likelihood that patients in whom the pulmonary circulation is affected (tetralogy of Fallot, Fontan, and pulmonary stenosis) have lower values in spirometry or body plethysmography. Reference Abassi, Gavotto and Picot23,Reference Ginde, Bartz and Hill39 In patients with left heart lesions, reviewed studies suggest fewer reduced or striking lung volume parameters. Reference Fabi, Balducci and Cazzato24,Reference Morales Mestre, Reychler, Goubau and Moniotte38
Secondly, lung volume reductions might be the result of a compliance lack in the thoracic cage: growth of the ribs, as well as adhesions in the pleural space, can reduce forced vital capacity. In a recent study, we could confirm that the reduction in lung volume is associated with the number of thoracotomies, Reference Müller, Ewert and Hager18 which supports this hypothesis of thoracic limitations. This reason can be improved by inspiratory training, which not only improves lung volume but also exercise capacity. Reference Hock, Remmele, Oberhoffer, Ewert and Hager54
Thirdly, the reduced lung volume can be due to the lack of exercise. The adult patients with CHD experience during their childhood due to overprotection by parents and physicians. Reference Bjarnason-Wehrens, Dordel and Schickendantz59 Nowadays, there are liberal recommendations for physical activity and sports. Reference Takken, Giardini and Reybrouck60 So, this should be confined to very few patients with CHD.
Only rarely the reduction of the lung volume is the result of a persistent post-operative phrenic palsy. Reference Lemmer, Stiller and Heise61 However – none of them highlighted any co-morbidities in the investigated patients. Further studies need to implement possible co-factors which influence lung parameter results (such as asthma and diaphragmatic palsy). Reference Healy, Hanna and Zinman19
Last but not least, heart failure with increased left or right heart might be present in early childhood and not be completely reversible with treatment. This condition will increase with time when more patients with CHD of moderate or severe complexity reach adulthood and step into a vicious cycle of heart failure, valve dysfunction and repeated surgery. As the heart and lung share the same thoracic cavity, every kind of dilatation or hypertrophy of a cardiac chamber results in a reduced lung volume.
Whatever the reason is, reductions in lung volumes are negatively associated with exercise performance, Reference Akam-Venkata, Sriram, French, Smith and Aggarwal55 and mortality, Reference Alonso-Gonzalez, Borgia and Diller36 and may indirectly also affect the heart itself. Patients with reduced or impaired lung function can only benefit if diagnosed early and treated if needed.
Therefore, at least a spirometry needs to be performed in every patient with CHD to detect initial restrictions of the lung volumes and possibly counteract deterioration through, for example, targeted sports Reference Gomes-Neto, Saquetto and da Silva e Silva52 or respiratory training. Reference Fritz, Müller, Oberhoffer, Ewert and Hager21,Reference Hock, Remmele, Oberhoffer, Ewert and Hager54 And the test needs to be interpreted in the context of the individual condition of the patient and the CHD by a trained person to guarantee the best result for both – the patient and the attending physicians.
Limitations
The sample size of the included studies reaches from 17 patients Reference Guenette, Ramsook and Dhillon25 to 1188 in Alonso-Gonzales et al. Reference Alonso-Gonzalez, Borgia and Diller36 Studies with no individual reference cohort consist of >50 subjects (two studies) or even >100 included patients. No study has applied a power analysis in its methods that justify the number of included patients. Furthermore, most of the included patients suffered from TOF or Fontan which makes it more difficult to precise results in general.
Studies that did not implement certain references for lung volumes were excluded since only a certain reference guarantees appropriate results which significantly reduced the number of studies.
Conclusion and Clinical Recommendation
Children, adolescents, and adults with CHD are affected by reduced forced vital capacity, measured via spirometry. Restrictive patterns are common. Further studies with more precise and different subgroups (in only one to two CHDs) are needed to further specify which CHD patients are at higher risk of decreased lung volumes. Furthermore, greater emphasis should be placed on body plethysmography, as possible restrictive patterns in the lung-volume pattern may originate from air trapping or other lung diseases.
All three aspects mentioned above (limited space in the thoracic, developmental limitations in the lungs, and risk of surgical interventions) need to be clarified. There is at least a national-wide need for a common database to stratify risk factors in CHD patients and to point out to parents and patients also concerning possible promotion and improvement possibilities in lung function. As seen in Fig 2, although patients reach normal values in forced vital capacity, FEV1 (above 80% of predicted), and its ratio are most likely below the reference represented as 100%.
Acknowledgements
The authors JH and LW were funded by an unrestricted grant from “Stiftung KinderHerz”. The sponsors had no role in study design, data collection, analyzing or interpreting results, or other matters relating to the paper. We declare that the results of the study are presented honestly and without fabrication, falsification, or inappropriate data manipulation according to the registered protocol. Additionally, we thank the whole team that was crucially responsible for its success.
Financial support
This research received no specific grant from any funding agency, commercial, or not-for-profit sectors.
Conflict of interest
None.
Contributorship statement
JH was responsible for the conception of the review, research process, assessment of applicable studies, and drafting of the manuscript. LW screened the studies as a second reviewer and gave important feedback on the studies and writing process. RDP, KR, PE, and AH gave important feedback on the review and improved the quality of the manuscript. All authors have read and approved the final version of the manuscript.
