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Controversies in the definition and management of insignificant left-to-right shunts
  1. Massimiliano Cantinotti1,
  2. Nadia Assanta1,
  3. Bruno Murzi1,
  4. Leo Lopez2
  1. 1Fondazione G. Monasterio CNR-Regione Toscana, Massa and Pisa, Italy
  2. 2Department of Pediatric Cardiology, Children's Hospital at Montefiore, Bronx, New York, USA
  1. Correspondence to Dr Massimiliano Cantinotti, Fondazione G. Monasterio CNR-Regione Toscana, Ospedale del Cuore, via Aurelia Sud, Massa 54100, Italy; cantinotti{at}ftgm.it

Abstract

Haemodynamically insignificant left-to-right shunts are frequently discovered when screening for congenital heart disease, resulting in significant economic and psychosocial impact.

A literature search was performed within the National Library of Medicine using the keywords small/insignificant/silent atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA) and patent foramen ovale (PFO). The search was refined by adding the keywords definition, classification and follow-up.

Our analysis revealed significant heterogeneity in the evaluation and management of innocent left-to-right shunts. The definitions for small defects vary greatly, making it difficult to distinguish between physiologic and pathologic lesions (eg, a PFO vs a true ASD). Most small defects will partially or completely resolve spontaneously early in life. If spontaneous resolution does not occur, the risk for long-term complications (such as embolic events and endocarditis) is low but poses several practical and ethical issues: immediate discharge versus long-term follow-up, duration and frequency of follow-up, and content and method of discussions with the parents. Additionally, there is controversy pertaining to treatment for PDAs and VSDs, particularly among interventional cardiologists, even though risk/benefit analyses are lacking.

Standards and guidelines using consensus opinion for the management of insignificant left-to-right shunts are needed to address the heterogeneity in diagnosis and management as well as use of resources, ethical and psychosocial issues.

  • Congenital Heart Disease
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Introduction

An innocent congenital heart disease (CHD) is an anatomic variant that cannot be classified as either physiologic or pathologic.1 ,2 Examples include a small atrial septal defect (ASD) or patent foramen ovale (PFO), small ventricular septal defect (VSD), and small patent ductus arteriosus (PDA).1 ,3 ,4 These lesions are seen frequently in most paediatric cardiology centres with great economic, personal and social impact.1–4 The easy availability of echocardiography has allowed for the diagnosis of tiny and frequently silent left-to-right shunts in otherwise normal patients. The exact significance of these minor anomalies, however, has not been determined, particularly in terms of whether they are true pathologic defects or anatomic or physiologic variants.1–4 Additionally, no clear guidelines exist on their definition and management.1–4

Their benign natural history is well known.1–4 In fact, patients with innocent lesions usually remain asymptomatic throughout their lifetime,5–20 and symptoms may occur but are improbable.21–53 This has prompted some regional registries to adopt stricter coding criteria for certain lesions,19 ,20 excluding neonatal lesions, such as PFOs and PDAs from classification as CHD.19 ,20

The necessity, modality and frequency of follow-up have also been debated. Some algorithms have been published,1 but these are old and have not been revised in the current era. More recent publications have recommended different management approaches. For example, many paediatric cardiologists follow patients with small ASDs regularly,2 ,18 and some advocate for closure of all PDAs.42 ,45 Not surprisingly, unnecessary follow-up and treatment have important consequences in terms of cost, human resources and parental anxiety.2 ,46 ,53 ,54

Study aim

The aim of this study is to review the literature pertaining to definitions and management approaches for haemodynamically insignificant left-to-right shunts.

Materials and method

Potential publications were identified from a systematic National Library of Medicine search (PubMed access to MEDLINE citations, http://www.ncbi.nlm.nih.gov/PubMed/) in December 2012. The search strategy included MeSH and free text terms for the key concepts small, insignificant, or silent ASD, VSD, PDA and PFO. The search was further refined by adding the keywords definition, classification, follow-up, natural history. Additionally, we identified other potentially relevant publications using a manual search of references from all eligible studies and review articles as well as from Science Citation Index Expanded on Web of Science. All papers were assessed independently by the three reviewers, and a consensus was reached for inclusion into the present study. The titles and abstracts of all the identified articles were evaluated and excluded if the manuscript was written in a language other than English.

Results

Literature search

Thirty-two publications were identified for potential study inclusion. Two non-English publications were excluded, leaving 30 for analysis.

Prevalence: the dimension of the problem

CHD occurs in 4–6 per 1000 live births,20 ,51 ,52 and left-to-right shunt lesions represent the majority.1 ,3 ,20 ,51 ,52 The incidence may be higher if silent lesions are also included.51 ,52 A recent publication from the metropolitan Atlanta area reveals that the most common defects seen between 1998 and 2005 were muscular VSDs, perimembranous VSDs, and secundum ASDs, with a prevalence of 27.5, 10.6 and 10.3 per 10 000 births, respectively.20 Similar results were seen in the 2004 Danish registry.54

Many left-to-right shunts present as silent defects with little clinical significance1–3 but with important economic and psychosocial implications as they represent a significant portion of routine clinical practice.1–3 In fact, a recent study reveals that PDAs, VSDs, innocent murmurs and branch pulmonary artery stenosis during infancy account for 91% of diagnoses for patients presenting with a murmur at a tertiary centre, and the decision to discharge versus follow-up is usually not consistent.3 Additionally, another study reveals that cardiology referral for evaluation of a Still’s murmur does generate parental anxiety.46

Patent foramen ovale and small interatrial defects

PFOs and small ASDs are frequently encountered during routine CHD screening.3 The prevalence of secundum ASDs is approximately 10.3–10.8 per 10 000 births.20 ,46–48 There are no standardised criteria to classify the size of ASDs7–18 and establish follow-up. Table 1 depicts different thresholds that have been used to classify defect size.8–13 More recent publications have defined ASDs as having a diameter >4 mm, and a PFO is no longer considered a CHD.19 ,20

Table 1

Atrial septal defects: classification and follow-up

However, a recent survey highlights the confusion over ASD size and the differences between a PFO and an ASD.18 Most cardiologists use the size or the presence of a flap to differentiate between the two, whereas others use the echocardiographic width of the jet traversing the septal opening, the visibility of the opening, or its location within the atrial septum. Different interpretations may lead to confusion in the management of the defects,18 particularly in terms of follow-up (table 1). More recent publications recommend a more prudent approach given the natural history of these defects.18

Defects with diameters <3 mm generally close or become smaller early in life,8 ,9 ,13 while those with diameters 3–6 mm9 ,11–13 close spontaneously in at least 80% of cases. By contrast, spontaneous closure is improbable in defects with diameters >8 mm,8 ,9 ,11–13 occasionally increasing in diameter over time. The presence of an atrial flap is more frequently associated with spontaneous closure,16 while an associated PDA may have a negative prognostic significance.16 The influence of prematurity has been identified as positive by some10 and negative by others.12 Some authors suggest that infants with ASD <3 mm do not need follow-up as they all close by 18 months of age.9

The definition of spontaneous closure has also been problematic, particularly since complete closure occurs in most patients with a small number having a residual hole that is significantly smaller than seen at presentation. Interestingly, the reported closure rate in some studies9 ,11 ,12 is discordant with the reported 25% prevalence of PFOs from other studies.2 ,55

For bigger defects with diameters of 6–7 mm after 1 year of age, yearly follow-up is recommended until 4 or 5 years of age.7 The survey described previously reveals that most paediatric cardiologists see patients with secundum ASD in follow-up on a yearly basis for small defects and more often for larger ones (40–45% see the patients at 6-month intervals).18 Patient age and the presence of symptoms are also important determinants in the frequency of follow-up in this study. Another survey from the UK reveals that, for children over 3 years old with an ASD and a normal right heart, 60% of physicians recommend follow-up every 3 years, 25% recommend follow-up every 5 years, and many recommend discharge in late adolescence.2 By contrast, for children over 5 years old with an incidental PFO, 81% recommend immediate discharge accompanied by a discussion of the implications of scuba diving. Only a small number recommend follow-up every year (8%) or every 3 years (10%) (table 1).

Small interventricular defects

Despite the fact that VSDs are the most common CHD,20 there are no clear criteria pertaining to management (table 2). Some authors have defined small VSDs as having diameters <3 mm by echocardiography,26 but other definitions have been published using other modalities.27 Normal pulmonary artery pressures and left heart size from echocardiography and a normal electrocardiogram are other criteria used to define small defects.2 Many studies have revealed a benign natural history for most VSDs.10 ,21–23 ,25 ,27 ,32–36 Muscular VSDs tend to close in 80% cases early in life,21 ,22 ,25 ,32–36 a frequency that is at least twice the frequency of spontaneous closure for perimembranous VSDs.25 Spontaneous closure may occur up to age 6 years25 or beyond school age for perimembranous VSDs.23 Interestingly, the presence of partially occluding accessory tissue is not predictive of spontaneous closure.23

Table 2

Ventricular septal defects: definition and natural history

At present, there are no standards for follow-up of small VSDs, though more frequent follow-up has recently been recommended. The UK survey previously described reveals that, for a thriving child over 6 months old with a small VSD, 67% advocate follow-up every 3 years, whereas 15% recommend annual follow-up.2 Most agree that these patients should be discharged as adolescents.

Published indications for VSD closure originate from an era with high operative mortality (up to 7.5%) and incidence of significant residual shunts (up to 20%). However, surgical correction for a small VSD in the current era is classified a low-risk procedure with only a 2% complication rate.56 Improved surgical techniques have led to revised recommendations for closure of small VSDs.29 ,30 Additionally, data on long-term sequelae for small VSDs have been discordant. Endocarditis occurs in 1.8–15%,27 ,31 aortic regurgitation occurs in 2–20%,27 and arrhythmias occur in up to 10% of cases.27 ,31 Differences in patient populations, classification systems, and management may explain some of these contrasting results.

Varied natural histories may also explain the heterogeneity in management for these patients. Some recommend surgery for all conal VSDs, VSDs with aortic valve prolapse (even without regurgitation), and VSDs associated with a harsh murmur persisting beyond age 5 years.30 By contrast, others suggest that surgery is not necessary if the pulmonary-to-systemic flow ratio is less than 2, there is no left ventricular volume overload, the pulmonary arterial pressure is not elevated, and there is no aortic regurgitation or associated symptoms27 (table 2).

Small patent ductus arteriosus

PDAs account for 10% of all CHDs with an incidence of 1 per 2000 term births.44 ,45 Small PDAs represent 3% of these cases. Up to 0.5% of patients with an innocent murmur have a small PDA.41 The definition of a small PDA has not been well established. Criteria to differentiate a small PDA with a characteristic murmur but no haemodynamic consequences from a very small and silent PDA have been proposed,45–47 but clear echocardiographic criteria have not been established (table 3).

Table 3

Definition of small/silent patent arterial duct and management indications

The age at diagnosis may be important. In a recent Atlanta CHD registry, PDAs are not considered CHD if the diagnosis is made in premature infants (gestational age <36 weeks) or in newborns (<6 weeks in age).19 Whether and how these children should be followed has not been discussed. In fact, there are no clear guidelines on the follow-up of small PDAs. In the same UK survey, for children over 3 years old with a tiny PDA, normal pulses, no heave, no ductal murmur, normal left heart size and normal pulmonary artery pressures, 46% recommend discharge, 35% recommend follow-up every 3 years and 14% recommend follow-up every 5 years.2 Two opposing recommendations emerge with free texting in the survey: one group favouring discharge and the other percutaneous closure.

Closure of large and haemodynamically significant PDAs is standard of care and can be performed safely and effectively with surgical or percutaneous methods. Small silent PDAs have been controversial with a clear division between intervention43 ,45 and conservative management.46 ,49 ,50 The remote risk of developing infective endocarditis (IE)34 should be weighed against the potential complications associated with intervention.37

The risk/benefit balance has been interpreted differently by various authors.44–50 A recent review states that only three cases of IE have been described in the past decade for silent PDAs,39 ,46–52 thereby estimating the risk of IE at around 0.01% per year (0.1% life-time risk over 85–90 years) using a conservative approach (a more liberal approach decreases the risk to 0.001% per year). They highlight the difficulty with accurate estimation of IE risk since prior studies do not take PDA size into consideration. Major adverse events for percutaneous PDA closure occur in 0.5–1.5%. Additionally, incomplete closure probably results in a higher IE risk than in similarly sized PDAs. Conservative estimates of the incidence of IE and percutaneous closure complications result in similar risk for closure versus non-closure, whereas more liberal estimates highlight the disadvantages of intervention.

Lastly, routine PDA closure represents a significant economic impact, with costs estimated at US$33 billion for IE prevention.39 ,49 Most recent works do not favour intervention for small PDAs,39 ,49 ,50 but closure is still recommended for all patients regardless of PDA size in some centres.45 ,47

Discussion

Defects characterised by haemodynamically insignificant left-to-right shunts occur frequently in paediatric cardiology outpatient centres,1 ,3 ,20 and their benign natural histories have been described, even before the advent of echocardiography.1 ,2 Published definitions and management approaches are heterogeneous, and issues related to cost, human resources and parental anxiety have not been addressed.1 ,3 ,46

Although technological advances have improved the standard of care, easy availability of imaging modalities may result in overdiagnosis, overusage of resources and increased parental anxiety.1–3 Clinicians may inappropriately rely on imaging studies to determine a lesion's clinical significance, creating an echocardiographic disease in lieu of traditional clinical skills.2 This results from vague classification systems, making it impossible to distinguish healthy from pathologic clinical states. For example, mitral valve prolapse represents an echocardiographic disease for which stricter diagnostic and management standards have evolved more recently.6

A similar issue exists for small left-to-right shunts. Echocardiography can detect small silent defects without associated symptoms or significant haemodynamic changes.1–3 Thus, differentiating between a pathologic (ASD) and physiologic condition (PFO) can be difficult.18 In fact, definitions for the same defects can vary from one cardiologist to the next.20

Guidelines for follow-up have also been discordant. Many of these defects spontaneously close completely or partially early in life. Their benign nature has been highlighted in recent CHD classification systems recommending that some neonatal conditions (such as a PFO, a ‘PFO vs ASD’, a PDA and branch pulmonary artery stenosis) not be coded as defects, but be considered as normal physiologic variants or complications of prematurity.20

If complete or partial closure does not occur, there is a low but real risk for long-term complications (such as an embolic event or endocarditis). This poses several practical and ethical issues. Should the patients be discharged immediately? Or should they be followed until spontaneous closure is documented? If there is no spontaneous closure, should they have indefinite follow-up? How frequently should they be evaluated? When should the lesions be treated? And what should physicians tell parents regarding the diagnosis and potential complications? Some authors suggest that after age 2 years, patients should be followed only once in late childhood and when they are almost fully grown.2 Others recommend closer follow-up and even treatment.

Evaluating the benefits and risks with treatment can be challenging. Small ASDs are likely to close incompletely with a PFO prevalence in the general population of 20–25%.46 And a PFO can be considered an anatomic or physiologic variant rather than a pathologic lesion despite the risk for cryptogenic stroke and migraine.2 In some centres, babies with a PFO are seen again at age 6 years and discharged even if the PFO remains open with strict instructions pertaining to the problems with scuba diving,2 though cost and resource usage issues have forced centres to re-evaluate this algorithm.

Small VSDs have a low but real risk for developing late complications, such as endocarditis, aortic regurgitation and arrhythmias, and improved results with surgery have induced some centres to revise their indications for surgery.30 Closure may remove the socioeconomic stigma associated with an uncorrected CHD, including limited access to insurance and employment opportunities. By contrast, other, more conservative centres prefer to follow these patients.27

Surgery is not free from complications, and the risk of IE does not completely disappear.27 ,30 Studies comparing surgical complications with the natural history of small left-to-right shunts have not been undertaken. Risk/benefit analysis are difficult to perform, mostly because of limited and heterogeneous data.41 This is further complicated by recent advances in percutaneous intervention, making treatment options, particularly for PDAs, more accessible. A recent review of small PDAs has shown that the risks with intervention outweigh the benefits.39 Additionally, systematic closure of all small PDAs is associated with significant economic impact.39 ,49 Yet some centres continue to close all PDAs regardless of size.43 Lastly, controversy remains regarding antibiotic IE prophylaxis for small PDAs and VSDs,39 despite the fact that recent guidelines do not recommend routine IE prophylaxis.57

Conclusion

Haemodynamically insignificant left-to-right shunts are frequently diagnosed by echocardiography, but controversies remain regarding their meaning and practical implications.

The lack of guidelines and standards has generated confusion in the severity classification and management of such defects, and whether follow-up and/or intervention are required has been debated. As a result, these common defects, although small, may pose a dilemma for the clinician. Consensus opinions are needed to establish a sustainable system for management and follow-up of specific lesions and to reduce unnecessary parental anxiety. These should include classification of defect size at different ages, as well as criteria to distinguish between physiologic and pathologic conditions. For defects such as a small VSD or silent PDA, one must balance the small risk associated with intervention against the rare long-term complications,27 ,31 particularly with the emergence of newer less invasive interventions. Algorithms to manage small left-to-right shunts must account for economic, social and ethical impact in order to establish a sustainable management approach. Lastly, attention must be paid to parental well-being with recommendations on what to say to prevent or attenuate parental anxiety.

References

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Footnotes

  • Contributors All the authors participated in the work and approved the final version.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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  • PostScript
    Massimiliano Cantinotti Nadia Assanta Bruno Murzi Giorgio Iervasi Isabella Spadoni