Article Text

The risk of misdiagnosis in acute thoracic aortic dissection: a review of current guidelines
  1. M Yousuf Salmasi1,
  2. Nina Al-Saadi1,
  3. Philip Hartley1,
  4. Omar A Jarral1,
  5. Shahzad Raja2,
  6. Muthana Hussein3,
  7. Julian Redhead4,
  8. Ulrich Rosendahl2,
  9. Christoph A Nienaber5,
  10. John R Pepper2,
  11. Aung Y Oo6,
  12. Thanos Athanasiou1
  1. 1 Department of Surgery and Cancer, Imperial College London, London, UK
  2. 2 Cardiac Surgery, Royal Brompton and Harefield NHS Foundation Trust, Harefield, UK
  3. 3 Emergency Medicine, Kingston Hospital NHS Foundation Trust, Kingston upon Thames, London, UK
  4. 4 Emergency Medicine, Imperial College Healthcare NHS Trust, London, UK
  5. 5 Department of Cardiology, Royal Brompton and Harefield NHS Foundation Trust, London, UK
  6. 6 Cardiac Surgery, Barts Health NHS Trust, London, UK
  1. Correspondence to Dr M Yousuf Salmasi, Surgery and Cancer, Imperial College London, London SW7 2BU, UK; y.salmasi{at}imperial.ac.uk

Abstract

Acute aortic syndrome and in particular aortic dissection (AAD) persists as a cause of significant morbidity and mortality despite improvements in surgical management. This clinical review aims to explore the risks of misdiagnosis, outcomes associated with misdiagnosis and evaluate current diagnostic methods for reducing its incidence.

Due to the nature of the pathology, misdiagnosing the condition and delaying management can dramatically worsen patient outcomes. Several diagnostic challenges exist, including low prevalence, rapidly propagating pathology, non-discrete symptomatology, non-specific signs, analogy with other acute conditions and lack of management infrastructure. A similarity to acute coronary syndromes is a specific concern and risks patient maltreatment. AAD with malperfusion syndromes are both a cause of misdiagnosis and marker of disease complication, requiring specifically tailored management plans from the emergency setting.

Despite improvements in diagnostic measures, including imaging modalities and biomarkers, misdiagnosis of AAD remains commonplace and current guidelines are relatively limited in preventing its occurrence. This paper recommends the early use of AAD risk scoring, focused echocardiography and most importantly, fast-tracking patients to cross-sectional imaging where the suspicion of AAD is high. This has the potential to improve the diagnostic process for AAD and limit the risk of misdiagnosis. However, our understanding remains limited by the lack of large patient datasets and an adequately audited processes of emergency department practice.

  • aortic dissection or intramural hematoma
  • cardiac imaging and diagnostics
  • cardiac computer tomographic (CT) imaging

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Introduction

Acute aortic dissection (AAD) is the most common thoracic aortic emergency. Along with intramural haematomas (IMH) and penetrating atherosclerotic ulcers,1 2 these three conditions collectively form the acute aortic syndrome (AAS).3 According to a UK population based study, AAD occurs at a rate of 6/100 000 (in a 10-year period).4 Furthermore, data from the Global Burden of Disease Study found that death from aortic aneurysm-related emergencies occurs at a rate of 2.4/100 000, and is the most common cause of death among conditions requiring emergency surgery in high-income countries.5

Aortic dissection is much less common than other causes of chest pain, yet far more lethal.6 Instantaneous aortic rupture can occur in 20% leading to immediate death.7 In type A AAD (involving the proximal aorta and arch) the cumulative mortality can be as high as 40%–50% within the first 48 hours.4 8 A further 1%–2% of patients die every hour unless life-saving treatment is initiated9 (figure 1). When comparing anatomical locations of the aorta affected, mortality from IMH has been found to be equivalent to that of AAD, and potentially higher when the ascending aorta is involved.10

Figure 1

Diagnostic pitfalls for aortic dissection. AD, aortic dissection; ED, emergency department

Malperfusion syndromes afflict up to a third of patients with AAD, both compounding the diagnostic process and compromising patients’ clinical state by perpetuating an inflammatory cascade stemming from end-organ ischaemia.11

Furthermore, treatment measures for other important differential diagnoses, namely acute coronary syndrome (ACS) and stroke, include anticoagulation and thrombolysis, which are profoundly deleterious in a patient with AAD. Patient outcome can be compromised if therapeutic measures are delayed or misappropriated. For survivors of AAD, a protracted therapeutic pathway increases the chances of haemorrhage, stroke, renal failure and poorer quality of life in the long-term. However, advances in surgery for type A AAD in the last four decades have improved survival from as low as 16% to up to 90%.12

Therapeutic measures in AAS begin from the emergency setting, including haemodynamic resuscitation and blood pressure control.13 Therefore a clinical system that fails to lead a patient to definitive treatment on presentation not only opens itself up to litigation,14 but has detrimental effects on patient outcomes. Quantifying the burden of misdiagnosis is challenging. Many published reports base their findings on coded data from emergency records, although emergency clinicians usually work on an evolving diagnosis, subject to the rapidly evolving patient condition. A recent national survey of UK based emergency departments (EDs) found that 58% of ED consultants were prepared to treat a chest pain condition for ACS based on ECG alone, even though symptoms mimicked AAD.15 Furthermore, 70% of EDs lacked a dedicated algorithm for diagnosing AAD.15

This review summarises the latest issues surrounding the misdiagnosis of AAD in EDs and critiques current guidelines in place for making the correct diagnosis in cases of AAS.

A diagnostic conundrum

The diagnostic dilemma in AAD is the obscure presentation and the rapid propagation of the disease: fast tracking the acutely ill patient to life-saving treatment becomes impeded by the higher chance of misdiagnosis or diagnostic delay. From arrival to the ED, the correct diagnosis being made in AAD can sometimes take several hours.16 It relies on the doctor thinking of the diagnosis, the patient evoking a clinical suspicion early on, thorough assessment and instigation of relevant investigations, all amidst an alternating clinical state. In summary, the main causes of diagnostic pitfalls are:

  • Symptoms can vary and sometimes be very minimal.

  • Acute aortic chest pain can mimic pain from other commoner acute conditions.

  • It is a rapidly developing syndrome, with evolving signs, symptoms and clinical state.

  • Poor sensitivity and specificity of basic first line investigations: vital signs, chest radiographs, ECGs.

  • There is no biomarker specific to aortic wall injury.

  • There are several possible imaging methods.

Subclassifying the factors leading AAD misdiagnosis allows for an appropriate focus on preventable causes, namely the diagnostic process and infrastructure (figure 2).

Figure 2

Risk factors for misdiagnosis in aortic dissection. AD, aortic dissection; ED, emergency department.

Clinical aspects of misdiagnosis

The majority of patients present with typical pain syndrome: a tearing pain in the centre of the chest radiating posteriorly. Where pain is minimal, misdiagnosis is more likely. Studies found that patients walking into the department were more likely to suffer AAD misdiagnosis.17 On the other hand, patients presenting in extremis, unlikely to give a coherent history or where symptoms can be obscure (secondary to malperfusion—as will be explained), are also at significant risk.18

Few signs are highly specific to AAD: the detection of signs such as a pulse deficit and/or discrepancy in blood pressure between the limbs are infrequent.19 Many patients may present with cardiorespiratory signs and symptoms as an exacerbation of underlying comorbidities, or a manifestation of complications of AAD. This can often lead clinicians down a different diagnostic track, especially when associated with a pleural effusion on chest radiography20 or a new onset cardiac murmur, where such signs will be mistaken as the sole explanation of the patient’s symptoms rather than complications of the underlying diagnosis of AAD.

Key diagnostic studies have used a pre-test probability score, which raises the suspicion of AAD and fast-tracks patients with acute chest pain towards a definitive diagnosis earlier. The three components of the risk assessment tool pertain to:

  1. Relevant history (connective tissue disease, known mutation, known thoracic aneurysm, family history, aortic valve disease).

  2. Pain features (eg, sudden onset, tearing nature, radiating to back).

  3. Clinical examination findings (eg, pulse deficit, blood pressure discrepancy, new murmur, focal neurology).

The presence of the above elements leads to a higher score and elicits a stronger suspicion of AAD for clinicians with a good specificity profile.21 22 Current American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines describe the strength of this score, although its formal inclusion into a clinical algorithm is yet to occur, perhaps due to the lack data from large studies on its use.

Aortic dissection with malperfusion

Malperfusion in conjugation with, and as a consequence of, AAD carries an additionally worse prognosis. This is primarily due to the aggravated clinical state of the patient, and also the higher risk of misdiagnosis secondary to accompanying non-linear clinical manifestations. Signs/symptoms of neurological deficit, abdominal pain, limb ischaemia and syncope and have all be reported in the literature as being potentially the sole presentation.23 24

The cause of malperfusion may be directly related to the dissection flap obliterating branch vessel ostia, false lumen protrusion into the branch vessel (with associated thrombosis) or due to a dynamic form of hypoperfusion related to the counterbalance of forces leading to collapse of the true lumen11 (table 1, figure 3).

Table 1

Malperfusion syndromes during an evolving aortic dissection

Figure 3

Anatomical diagram of an evolving type A aortic dissection (DeBakey I) and associated malperfusion syndromes. The labels (A–G) correspond to descriptions in table 1.

Importantly, malperfusion is a clinical state and may not always correlate with radiological findings,25 indicating the importance of the patient’s clinical assessment, biochemical results and vital signs over time, thus providing a holistic picture for the likelihood of tissue ischaemia and allow for more targeted management. Treating AAD with visceral or lower limb malperfusion requires the following: (i) definitive treatment of the site of dissection (surgical or endovascular); (ii) restoring blood flow to the malperfused organ (table 1). The first is a necessary treatment to eliminate the source ailment and ensure patient survival, while the second aims to correct the metabolic disruption and limit the systematic inflammatory response, thus improving the clinical state of the patient and recovery from the treatment process overall. Addressing both is critical, however the order in which prioritise the two treatments is debatable (especially in type A AAD) and requires a carefully planned patient-specific management strategy.26 27

Coronary malperfusion

Disruption to coronary perfusion in the setting of type A AAD occurs in up to a third of cases20 and raises key issues in its diagnosis:

  • Thoracic aortic pain can mimic angina.

  • Acute coronary syndrome (ACS) is more common than AAD/AAS and is therefore preferentially suspected by clinicians.

  • Early treatment in ACS (antiplatelet agents, anticoagulation, thrombolysis) are deleterious for patients with AAD.

The proportion of patients eventually diagnosed as AAD who receive a prior emergency diagnosis and/or management plan for ACS can be as high as 80%.28 Troponin positivity is common in AAD, and, rather than a direct result of aortic wall injury, can be secondary to:

  • Dissection propagating into coronary artery.

  • Occlusion of coronary ostia by the dissection flap.

  • AAD causing shock or left ventricular compromise in patients with pre-existing coronary artery disease

Vagnarelli and colleagues29 found that troponin positivity led to a significantly increased risk of delay in correct diagnosis, as well as an increased administration of thrombolytic therapy. This was also confirmed by Hansen et al 30 who found a significantly increased rate of pulmonary and pericardial haemorrhage (online supplementary appendix).

Supplemental material

Current guidelines for acute aortic syndrome

The latest AHA13 and ESC3 guidelines in the management of aortic disease stipulate that managing patients with AAD in a timely fashion is paramount, although little is mentioned on ways to minimise or rectify misdiagnosis of the condition.

In the latest ESC guidelines for ST-elevation myocardial infarction there are several key management algorithms,31 which have the advantages of being time sensitive, multi-stage and address the ways to minimise diagnostic delay, while incorporating clear treatment strategies. Comparatively, the guidelines for the management of aortic conditions, both from the AHA13 and ESC,32 offer far fewer strategies to fast track patients through diagnosis, urgent management and institutional transfer. A review of recommendations by the American College of Emergency Physicians was published in 201533 recommending the use of diagnostic tests and initial management.

The lack of consensus in the AAS management is likely due to the lack of large data sets and registries compared with other acute conditions attending the ED. To date, the International Registry for Aortic Dissection (IRAD) published a single study in the topic area34 (N=894, period 1996–2007), and found three main factors relating to delayed diagnosis: female gender, atypical symptoms (especially fever) and presentation to non-tertiary hospital.34 Other data series and population studies on AAS have also been published although the topic of misdiagnosis has not been addressed.4 35 A summary of studies investigating clinical predictors of misdiagnosis is included in the online supplementary appendix.

The use of diagnostic tests: biomarkers

The lack of a highly specific biomarker is one of the main hindrances in diagnosing AAD quickly and effectively. At present, the use of D-dimer perhaps has the most clinical utility, particularly because of its good negative predictive value for AAD (up to 97.6%), having the best diagnostic performance in the first 6 hours.36 Its use in the acute setting is often variable due to its low specificity (46.6%) and overlap with other clinical conditions, including ACS.37 A recent large prospective multicentre study (n=1850) found the negative predictive value of a bi-pronged triaging method (D-dimer testing and the three-element AAD risk detection score) to be higher than the use of D-dimer alone (99.7 vs 99.2%).22 Other potential biomarkers include calponin, smooth muscle myosin heavy chain (smMHC), elastin and circulating micro-RNAs.38 However, there are practical drawbacks to consider including rapidly diminishing levels within the first 24 hours (as with smMHC), poor positive predictive values (as with calponin) and low levels in thrombosed false lumens (as with elastin). These tests rely on ELISA which take up to 24 hours to provide a result, inhibiting their applicability in a condition that needs a timely diagnosis.

The use of diagnostic tests: imaging

CT scanning is now the most popular first line imaging method (73%),39 being quick, non-invasive and having increasing prevalence of ECG-gating technology, thus improving its diagnostic accuracy. Although the use of trans-oesophageal echo (TEE) has fallen from 50% to 23%, it can offer excellent diagnostic accuracy in addition to complimentary data for surgical repair.40 Focused transthoracic echocardiography during emergency assessment can reduce AAD misdiagnosis41 and help rule out other differentials, especially when other imaging modalities are not available.

The challenge in diagnosing AAD via imaging is compounded by its dynamic nature, where a small tear may be missed on initial scanning, developing quickly into a more extensive dissection which is detected at a later scan, or even open surgery.42 43 As such, patients who appear clinically well can quickly deteriorate into a critical state between closely associated time points. The variability in the extent of intimal disruption in AAD, described in the Svensson classification,43 may explain the inconsistency in presenting features and diagnostic sensitivity.

Towards an improved algorithm for AAD

Improving the detectability of AAD within a diagnostic framework for acute chest pain is challenging: its incidence among all chest pain presenters can be as low as 0.09%.44 In contrast, up to 75% of presenting patients are found to have non-serious causes of their pain.44

Incorporating early risk scoring for AAD alongside validated scores for related life-threatening causes of chest pain (eg, Emergency Department Assessment of Chest Pain Score (EDACS) for ACS,45 Wells’ score for pulmonary embolism46 may accelerate the diagnostic pathway and instigate targeted treatment quickly.(figure 4)

Figure 4

ED diagnostic processes for acute chest pain with targeted risk scoring and management. Quoted percentages are adapted from Kohn et al.44 AAD, acute aortic dissection; ACS, acute coronary syndrome; BP, blood pressure; CAD: coronary artery disease; CT: computerised tomography; DVT, deep vein thrombosis; ED, Emergency department; EDACS, Emergency Department Assessment of Chest Pain Score; PE: pulmonary embolus; STEMI, ST-elevation myocardial infarction.

Diagnostic uncertainty should be recognised early and stimulate the timely inclusion of alternative diagnostic tools. Especially in patients with low AAD risk and/or EDACS scores, urgent echocardiography should be considered,41 with the ability to rule out ventricular hypokinesia or akinesia, or better still identify a dissection flap (although with low sensitivity). Rapid biomarker assessment is critical: suspicious signs, symptoms, risk scores and deteriorating clinical states should prompt the early request of troponin and D-dimer. This should be balanced against the knowledge that D-dimer can at times (although rare) be negative in AAD,47 and troponin positivity does not strictly rule out the diagnosis.29 30 Therefore, non-indicative blood results should not preclude the need for definitive imaging if the suspicion of AAD were high. This correlates with the guidelines for acute pulmonary embolism, allowing patients with a high clinical suspicion to be fast-tracked to CT angiography without the need for a D-dimer result.46

Early working diagnoses in ACS is important: it is more common than AAD in acute chest pain by up to 40-fold.44 However, commitment to ACS prior to more detailed investigations has resulted in many reported incidences of misdiagnosed AAD.28 30 48 An emphasis on patient reassessment and diagnostic review is therefore needed, particularly in cases of deteriorating patients, altering clinical states (eg, new onset of malperfusion signs) or definitive rule out of ACS.

AAD patients presenting with malperfusion syndromes will not fit into a chest pain pathway. Interventions to improve diagnostic accuracy in these patients need to focus on limiting the potential of being ‘anchored’ with these potentially misleading presentations. This will involve, for example, the consideration of CT imaging for obscure or intractable clinical states, or extending imaging protocols anatomically as part of a stroke evaluation or assessment for lower limb ischaemia.

Workforce planning also means that tertiary centres are sparsely located among geographical regions, and the availability of a regional AAD team/surgeon can be unknown, emphasising the need for improved referral pathways and transport methods. A recent study from the IRAD revealed that the mere fact of patients requiring inter-institutional transfer from the ED to the surgical unit meant that patients caused a mean delay of 1.7 hours from the time of diagnosis to treatment.49

Future directions

The pathological process of AAD makes the use of applied algorithms quite different to other conditions: the discrete manifestation of the disease, the sporadic presentation (to varyingly equipped EDs across the country) and the rapid propagation (prevailing the need for urgent transition to a tertiary centre), bring several process entities, functions and events into the analytical process, not without mentioning the human factors also associated.

Reducing the incidences of AAD misdiagnosis is likely to become achievable from the assimilation of large amounts of real patient data from registries and employing meta-analytical and data synthesis methods to generate more robust clinical decision systems, ideally using artificial intelligence.

Systems engineering, evolved from industrial engineering, is the science that assimilates the design, control and orchestration of systems activities in order to meet performance objectives. When applied to healthcare, the science can provide useful analytical methods to optimise disease management processes. Stochastic modelling would be particularly useful in the acute aortic syndrome, as it takes into account the pluralistic nature of the process and the variety of the pressures of error that exist. It also makes use of Markov Decision Processes, which provide a mathematical framework for modelling decision making where outcomes are partly random (influenced by the disease process) and partly under the control of the decision maker (influenced by the clinician and investigations affected).50

Conclusion

The correct diagnosis of AAD relies on a synthesis of many aspects of the history, examination and clinical investigations, coupled with a high index of clinical suspicion and attention to detail throughout the process. Moving forward, reducing the incidence of misdiagnosis requires a revision of current guidelines and finding a balance between algorithms of similarly presenting pathologies.

References

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Footnotes

  • Contributors MYS and TA are responsible for the overall content of the manuscript. Specific contributions: MYS: conception, manuscript preparation, writing, data collection, analysis, review. NAS, PH: writing, data collection, review. OAJ: writing, review. SR: review. MH, JRP, UR: review. CAN, JRP, AO, TA: conception, review.

  • Funding This study was supported by the NIHR Imperial College Biomedical Research Centre (P69559).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

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

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