Clinically relevant pathologies

In order for routine TTE screening of newly diagnosed patients with AF to be successful, the screening would need to identify pathologies which would not usually be identified by the time of AF diagnosis, and which would result in a change in clinical management. These were not restricted to pathologies affecting decisions about anticoagulation. Factors affecting routine screening programmes are reported in Chapter 1 (see Factors associated with successful screening programmes).

Pathologies were selected according to the following inclusion/exclusion criteria.

Inclusion:

1. The pathology could occur in patients with AF.
2. The pathology is detectable by TTE.
3. A positive diagnosis would lead to a change in clinical management.

Exclusion:

1. The pathology would necessarily be diagnosed prior to AF diagnosis (e.g. congenital abnormalities that would have been diagnosed in infancy) or at the time of AF diagnosis (i.e. would be diagnosed by ECG).
2. The pathology would necessarily be clinically diagnosed without echocardiography.
3. The pathology presents with symptoms that represent indications for which a patient would receive TTE regardless of AF diagnosis, including indications for emergency TTE.

Based on the above inclusion and exclusion criteria, the following pathologies were selected, and for ease of reporting were grouped into the following categories.

1. Structural heart defects This category comprised atrial septal defect, ventricular septal defect and rupture of the chordae tendineae or papillary muscle.
2. Ischaemia or thrombosis This category comprised atrial and ventricular thrombosis, atherosclerotic heart disease and aneurysm of the heart.
3. Pulmonary disease This category comprised PE and hypertension, and cor pulmonale.
4. Endocarditis This category comprised infective and non-infective endocarditis.
5. Valvular heart disease This category comprised valvular regurgitation/incompetence/insufficiency or stenosis of one or more of the mitral, aortic, tricuspid or pulmonary valves.
6. Cardiomyopathy This category comprised hypertrophic obstructive or non-obstructive or dilated cardiomyopathies, and included LV non-compaction.
7. Heart failure This category comprised CHF, LV dysfunction or impairment, LA enlargement and RV dysfunction.
8. Diseases of arteries This category comprised aortic dissection.
9. Cardiac masses This category comprised cardiac tumours or masses.

Examples of excluded pathologies are given in Appendix 1.

For some, but not all, of the selected pathologies, TTE/TOE are considered the gold standard for diagnosis (see Appendix 2).

Identification of studies

A comprehensive search was undertaken to systematically identify studies assessing the diagnostic accuracy of TTE for the clinically relevant pathologies as described above (see Clinically relevant pathologies).

The search strategy comprised the following main elements: searching of an electronic database; contact with experts in the field; and scrutiny of bibliographies of retrieved papers. Owing to the large number of references identified by the search, the search was restricted to MEDLINE. The MEDLINE search strategy is presented in Appendix 3.

Literature searches were conducted from March to August 2010. References were collected in a database and duplicates removed.

Inclusion and exclusion criteria

Data abstraction, critical appraisal strategy and synthesis

Data were extracted by one reviewer using a standardised data extraction form and checked by another reviewer. Discrepancies were resolved by discussion. Where needed, sensitivity was calculated as the number of TPs divided by the sum of the number of TPs and the number of FNs. Specificity was calculated as the number of TNs divided by the sum of the number of TNs and the number of FPs. Where possible, confidence intervals (CIs) were calculated based on the Gaussian formula from Newcombe:⁵⁸

Quality assessment involved assessing the study type according to the hierarchy of Merlin et al.⁵⁷ This takes into account whether studies of test accuracy use consecutive patients, and whether assessors are blinded to other test results (see study types in Inclusion and exclusion criteria, above).

Further quality assessment was based on QUADAS (quality assessment of studies of diagnostic accuracy included in systematic reviews) criteria.⁵⁹

Data extraction forms are in Appendix 4. Quality assessment forms are in Appendix 5.

Data were tabulated and discussed in a narrative review.

Identification of studies

A comprehensive search was undertaken to systematically identify clinical effectiveness literature concerning the prevalence of clinically important pathologies in patients with AF. To obtain the best estimates, the search was restricted to studies with the objective of assessing prevalence.

The search strategy comprised the following main elements: searching of electronic databases; contact with experts in the field; and scrutiny of bibliographies of retrieved papers.

The following databases were searched from inception: MEDLINE; MEDLINE in Process (for latest publications); EMBASE; The Cochrane Library, including the Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register (CCTR), Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED) and Health Technology Assessment (HTA) databases; NIHR Clinical Research Network Portfolio database; National Research Register (NRR) Archive; Web of Science (WoS) Conference Proceedings; Current Controlled Trials (CCT); ClinicalTrials.gov. Searches were not restricted by date or publication type.

The MEDLINE search strategy is presented in Appendix 3.

Literature searches were conducted from March to August 2010. References were collected in a database, and duplicates removed.

Inclusion and exclusion criteria

Data abstraction, critical appraisal and synthesis

Data were extracted by one reviewer using a standardised data extraction form and checked by another reviewer. Discrepancies were resolved by discussion.

Quality assessment, for studies with the intended outcome of prevalence of a pathology, was based on criteria identified in the STROBE statement (Strengthening the Reporting of Observational Studies in Epidemiology).⁶⁰

Data extraction forms are provided in Appendix 6. Quality assessment forms are in Appendix 7.

Data from studies designed to detect the prevalence of a particular pathology were tabulated. Owing to heterogeneity of populations, pathologies and comparators, data synthesis was precluded. These data were discussed in a narrative review.

Diagnostic accuracy of transthoracic echocardiography for clinically relevant pathologies

Quantity and quality of research available

The literature search yielded 15,824 article citations when duplicates had been removed. Figure 1 shows study selection, in a modified version of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram.⁶¹ Citations presenting purely economic analyses were not included in this chapter. References excluded at the full paper screening stage (n = 38), with reason for exclusion, are presented in Appendix 8.

FIGURE 1

Study selection for diagnostic review.

There were 44 diagnostic accuracy studies^62–105 and five prognostic studies^106–110 accepted into the review.

A summary of included diagnostic accuracy studies is presented in Table 1 and a summary of included prognostic studies is presented in Table 2.

TABLE 1

Summary of diagnostic accuracy studies

TABLE 2

Summary of prognostic studies

Of the 44 included studies,^62–105 there were 17 studies^{62,69,72,74,75,77,79,80,82,86,90,91,95,97,100–102} that included AF patients in the population. Of these, for two studies^79,91 all participants had AF. Although two studies^63,71 stated that there were no patients with AF in the population, in other studies it was not reported.

For all categories of pathologies sought, studies of diagnostic accuracy were identified. AF population studies were available for the categories of structural defect, ischaemia/thrombosis, pulmonary disease and valvular heart disease.

Methods of TTE represented were 2D, M-mode, pulsed and continuous wave Doppler, and colour Doppler. All studies had a high percentage of usable, good images from TTE.

All five prognostic accuracy studies included^106–110 had a population of non-valvular/non-rheumatic AF. Of the categories of pathologies sought, only heart failure and valvular heart disease were represented. Three of the studies were prospective studies^106,107,110 with follow-up ranging from mean 1.3 to 9.6 years. Two of the studies^108,109 were retrospective. The TTE methods represented were 2D, M-mode and colour Doppler.

Diagnostic accuracy results

Eight studies^{64,78,86,92,96–98,105} reported diagnostic accuracy of TTE in structural defects (Table 3). TTE was presumed the gold standard for one study of ventricular septal defect.⁶⁴ Sensitivity ranged from 0.25 for atrial septal hypertrophy⁸⁶ to 1 for ostium primum atrial septal defect⁹⁶ or ventricular septal rupture.⁹⁸ Two studies^86,97 reported specificity, which ranged from 0.9 for rupture of chordae tendineae⁹⁷ to 0.909 for atrial septal hypertrophy.⁸⁶ Six^{78,92,96–98,105} of the eight studies used catheterisation, surgery or autopsy as the comparator diagnostic test, whereas one used clinical cardiac examination,⁶⁴ and one used TOE⁸⁶ (see Table 3).

TABLE 3

Structural defect

Nine studies^{62,77,79,82,90,91,95,100,102} reported diagnostic accuracy of TTE in ischaemic heart disease (Table 4). Sensitivity ranged from 0 for right atrial appendage (RAA)⁷⁹ or left atrial appendage (LAA)¹⁰² thrombus to 0.955 for thrombosis of ventricle.¹⁰⁰ Specificity ranged from 0.857 for thrombosis of ventricle¹⁰⁰ to 1 for LA⁷⁹ or right atrial (RA)⁷⁹ thrombus. Five of the studies^{62,77,90,95,100} used surgery or angiography, three used TOE^82,91,102 and one used CT⁷⁹ as comparators (see Table 4).

TABLE 4

Ischaemia/thrombosis

Two studies^66,80 reported diagnostic accuracy of TTE in pulmonary disease (Table 5). Sensitivity ranged from 0.523 for PE⁶⁶ to 1 for pulmonary hypertension.⁸⁰ Specificity ranged from 0.6 to 1 for pulmonary hypertension.⁸⁰ The study of PE⁶⁶ used perfusion lung scan with radiography or pulmonary angiography as a comparator, whereas the study of pulmonary hypertension⁸⁰ used catheterisation (see Table 5).

TABLE 5

Pulmonary disease

Three studies^67,76,94 reported diagnostic accuracy of TTE in endocarditis (Table 6). Sensitivity ranged from 0.44⁹⁴ to 0.871;⁶⁷ specificity ranged from 0.615⁶⁷ to 0.98.⁹⁴ Two of the studies used TOE as a comparator,^67,76 whereas the other study⁹⁴ used information obtained from clinical follow-up (see Table 6).

TABLE 6

Endocarditis

Twelve studies^{64,65,68,69,72–75,88,101,103,104} reported diagnostic accuracy of TTE in valvular heart disease (Table 7). TTE was presumed gold standard for four studies of MR,^64,68 aortic stenosis,^64,68 mitral valve prolapse (MVP),⁶⁴ valvular heart disease,^64,88 aortic regurgitation (AR)^64,68 and tricuspid regurgitation.⁷³ Sensitivity ranged from 0.222 for mitral stenosis leaflet calcification¹⁰³ to 1 for mitral stenosis¹⁰⁴ or mitral regurgitation⁷⁵ or severe AR.⁶⁹ Specificity ranged from 0.655 for mitral stenosis to 1 for AR or MR. Six of the studies used catheterisation/aortography or radiography/cinefluorography as comparators,^{69,74,75,101,103,104} four of the studies used clinical examination,^64,65,68,88 one used TOE⁶⁸ and one used CT⁷³ (see Table 7).

TABLE 7

Valvular heart disease

One study⁸⁵ reported the accuracy of TTE in differentiating between ischaemic and non-ischaemic cardiomyopathy (ICM and non-ICM) (Table 8). This study reported a sensitivity of 0.77 and specificity of 0.77 for differentiating between ICM and non-ICM with a comparator of angiography.

TABLE 8

Cardiomyopathy

Five studies^{63,71,81,87,99} reported accuracy of TTE in the diagnosis of heart failure (Table 9). TTE was presumed the gold standard for two studies of CHF⁸¹ and LV dysfunction.⁹⁹ Sensitivity ranged from 0.737 for CHF⁶³ to 0.93 for LV hypertrophy.⁸⁷ Specificity ranged from 0.75 for CHF⁶³ to 1 for LV dysfunction.⁷¹ Two of the studies used clinical diagnosis as comparators,^81,99 two studies^63,71 used radiography or catheterisation, and one used autopsy results⁸⁷ (see Table 9).

TABLE 9

Heart failure

Four studies^70,83,84,89 reported diagnostic accuracy of TTE in aortic dissection (Table 10). Sensitivity ranged from 0.593⁸³ to 0.953.⁸⁹ Specificity ranged from 0.508⁸⁹ to 0.977.⁸⁹ Three studies^83,84,89 included surgery, autopsy or angiography as comparators; the other study used aortography⁷⁰ (see Table 10).

TABLE 10

Diseases of arteries

One study⁹³ reported the diagnostic accuracy of TTE for intracardiac masses (Table 11). This study reported sensitivity 0.882 and specificity 0.953, with a comparator of surgery.⁹³

TABLE 11

Tumours or cardiac masses

Prognostic study results

Five studies^106–110 reported prognosis based on TTE-diagnosed pathologies in AF populations.

The pathologies were left atrial diameter (LAD); mitral annular calcification; MVP global, moderate to severe or reduced LV systolic dysfunction; any or severe MR; and valvular abnormality (Table 12).

TABLE 12

Prognosis based on TTE-diagnosed pathologies in AF

Prognosis was investigated by studies for the types of valvular heart disease, mitral annular calcification, MVP, MR and valvular abnormality. Mitral annular calcification was non-significantly associated with thromboembolism by age-adjusted analysis RR of 0.6 (95% CI 0.2 to 1.5; p > 0.2).¹¹⁰ MVP had a non-significant association with risk of stroke unadjusted RR of 0.29 (p = 0.22).¹⁰⁶ For MR, grade 1 MR (compared with no MR) odds ratio (OR) of 2.689 (95% CI 1.039 to 7.189; p = 0.0434) was significantly associated with history of thromboembolic events.¹⁰⁸ Severe MR had a non-significant association with risk of stroke (relative to none or mild MR) unadjusted RR of 1.7 (p = 0.59),¹⁰⁶ was found to be protective against stroke with hazard ratio (HR) of stroke for increase in MR from mild to severe groups 0.45 (95% CI 0.20 to 0.97) by multivariate analysis (multivariate analysis includes MR, LAD, sex and age),¹⁰⁹ and was non-significantly associated with thromboembolism by age-adjusted analysis RR 0.4 (95% CI 0.1 to 3.0; p > 0.2).¹¹⁰ For MR, the retrospective studies^108,109 found significant associations with prognosis, whereas the prospective studies^106,110 had non-significant results. Any detected valvular abnormalities had a reported HR for mortality: diabetic participants 2.05 (95% CI 1.10 to 3.82; p = 0.0229), non-diabetic participants HR 1.88 (95% CI 1.30 to 2.70; p = 0.0007).¹⁰⁷ For this study, diabetics and non-diabetic groups differed in that diabetic participants were older and had higher comorbidity, and more of them received oral anticoagulation; there was also a relatively small number of diabetics.¹⁰⁷

Left atrial diameter had a reported non-significant association with risk of stroke unadjusted RR of 1.02/mm (95% CI 0.99 to 1.06; p = 0.10¹⁰⁶) and was reported to have HR of stroke for every 10-mm increment in LA size of 1.06 (95% CI 0.75 to 1.49) by multivariate analysis (multivariate analysis includes MR, LAD, sex, age).¹⁰⁹ LAD (corrected for body surface area) as a continuous variable by univariate analysis was significantly associated with thromboembolism (p = 0.01¹¹⁰), and had reported HR for mortality, diabetic participants 1.01 (95% CI 0.97 to 1.05; p = 0.6445), HR non-diabetic participants 1.06 (95% CI 1.03 to 1.08; p < 0.0001).¹⁰⁷ Moderate to severe LV dysfunction was associated with a significantly higher risk of stroke relative to normal LV function or mild dysfunction,¹⁰⁶ and global LV dysfunction was significantly associated with risk of thromboembolism.¹¹⁰ Reduced LV function had reported HR for mortality, diabetic participants 1.52 (95% CI 0.85 to 2.70; p = 0.1598), HR non-diabetic participants 2.28 (95% CI 1.58 to 3.29; p < 0.0001).¹⁰⁷

Results of prevalence review

Quantity and quality of research available

The literature search yielded 8316 article citations when duplicates had been removed. Figure 2 shows study selection, in a modified version of the PRISMA flow diagram.⁶¹ References excluded at the full paper screening stage (n = 15), with reason for exclusion, are presented in Appendix 9.

FIGURE 2

Study selection for prevalence review.

There were 16 prevalence studies^28,111–125 accepted into the review. Some of the studies investigated the prevalence of more than one pathology.

A summary of included prevalence studies is presented in Table 13.

TABLE 13

Summary of prevalence studies

Prevalence studies were found for the following categories of pathologies: structural defect, ischaemia/thrombosis, valvular heart disease, cardiomyopathy and heart failure.

The assessment of methodological quality of included studies was performed using the recommended guidelines in the checklist for the STROBE statement.¹²⁶ Features of the study considered were information regarding the study's rationale and objectives, study design (including methods of recruitment and assessment), reporting of results and measures used to address confounding factors. The criteria and characteristics of individual studies are shown in Appendix 7.

Of the 16 studies that provided data for the review of the prevalence of clinically significant pathologies in patients with AF, seven studies^{28,112,114,115,119,121,124} were retrospective in design, eight^{113,116–118,120,122,123,125} were prospective studies, and one¹¹¹ was a case–control study.

Patients with AF were identified mainly by ECG, either at the time of recruitment or from hospital notes such as admissions notes or discharge records. Five studies did not report the methods used to verify the presence or history of AF in eligible patients^{112,114,120,124,125} although one study gave details in a prior publication⁹⁸ and the others used candidates for cardioversion giving confidence in accuracy of diagnosis. Although two retrospective studies^28,121 used TOE and TTE in diagnosing the presence of ischaemic heart disease, the methods used to diagnose the presence of coexisting clinically significant cardiac pathologies were not detailed in three studies.^115,118,119 The remaining studies relied on TOE and provided information on diagnostic criteria for pathologies of interest. Detailed descriptions of the assessors evaluating eligible patients regarding pathologies of interest were reported in four studies;^{113,114,116,123} for one of these studies,¹¹³ the relevant information was reported in a separate publication.¹²⁷ In one study,¹¹⁶ outcome data were incomplete; the reason was that TOE provided inadequate visualisation of the pathology of interest in a number of patients.

All methodological quality criteria of interest were met in six studies.^{111,113,117,122,123,125} At least one of the criteria was not satisfied in three studies,^28,114,116 the criteria were partially met in one study¹¹⁵ and information was unclear in two studies.^112,120

Prevalence results

One prevalence study¹¹⁹ was identified that sought to identify prevalence of atrial septal defect, as presented in Table 14. This study, by Lip et al.,¹¹⁹ found a prevalence of 0.9% for atrial septal defect. This study looked at a cross-section of patient records in UK primary care.

TABLE 14

Prevalence study structural defect

Fifteen studies^{28,111–114,116–125} investigated the prevalence of pathologies within the category ‘ischaemia/thrombosis’, as shown in Table 15. One study, that by Lip et al. 1997,¹¹⁹ found a 28.8% prevalence of ischaemic heart disease.

TABLE 15

Prevalence studies: ischaemia/thrombosis

The six studies^{112,116,117,120,124,125} reporting prevalence of LA thrombus gave differing prevalences, ranging from 3%¹¹⁷ to 18%.¹¹⁶ Both of these studies^116,117 used TOE to diagnose thrombi. These six studies differed in terms of sample size and population, with Maltagliati et al.¹²⁰ including atrial flutter, Shen et al.¹²⁴ restricting the population to patients with subtherapeutic INR, and Kleeman et al.¹¹⁷ using a population admitted for cardioversion.

Six studies^{28,114,120–123} investigated prevalence of LAA thrombi; the lowest reported prevalence was for patients undergoing catheter ablations 1.6%¹²³ and the highest was 40%,¹²² although this study had a small sample size (n = 30). Two studies^28,120 looked at RAA thrombus, reporting prevalences of 0.5%¹²⁰ and 6.7%.²⁸ Both of these studies used TOE to diagnose thrombi.

Four studies^{115,118,119,122} investigated the prevalence of valvular pathologies (Table 16). Two of these studies^115,119 reported prevalence of valvular heart disease as 13.4%¹¹⁵ to 26.1%,¹¹⁹ and combining rheumatic and non-rheumatic valvular heart disease from Levy et al.¹¹⁸ would give 18.8% prevalence. Mitral valve disease had a reported prevalence of 10.4%,¹¹⁵ and Santiago et al.¹²² reported prevalence of 30% for MR.

TABLE 16

Prevalence studies: valvular heart disease

Three studies^115,118,119 investigated the prevalence of pathologies within the category cardiomyopathy, as presented in Table 17. Dang et al.¹¹⁵ and Lip et al.¹¹⁹ reported prevalences of 4.5%¹¹⁵ to 5.4%.¹¹⁹ Levy et al.¹¹⁸ reported a prevalence of 4.5% for hypertrophic cardiomyopathy and of 9.2% for dilated cardiomyopathy.

TABLE 17

Prevalence studies: cardiomyopathy

Two studies^115,118 investigated the prevalence of heart failure, as shown in Table 18. Dang et al.¹¹⁵ reported a prevalence of 31.1% and Levy et al.¹¹⁸ reported the prevalence of CHF to be 29.8%.

TABLE 18

Heart failure

Discussion of clinical effectiveness

Diagnostic accuracy studies with AF populations were available for the pathologies atrial septal defect, atrial septal aneurysm, rupture of chordae tendineae, atrial thrombosis, ventricular thrombosis, coronary artery stenosis, pulmonary hypertension, aortic and MR, and tricuspid stenosis. Diagnostic accuracy studies without reported AF populations were available for other pathologies, including endocarditis, cardiomyopathy, heart failure, LV dysfunction, aortic dissection and cardiac masses. As the search was limited to MEDLINE, it is possible that the database search will have missed some studies, although additional bibliography and hand-searching identified only a small proportion of articles to be screened, and the database search identified diagnostic studies for almost all the pathologies selected as relevant. Thus diagnostic accuracy data were available for a range of relevant pathologies, although data were not available for all pathologies in an AF population. There was considerable heterogeneity between studies, especially in terms of population and pathology being identified, and in comparator diagnostic technique, with some heterogeneity in the type of TTE used and the study type.

Diagnostic accuracy showed high specificities for all selected pathologies, with the majority having specificity of 0.8 or higher, meaning a low proportion of FPs. For most pathologies there was also quite high sensitivity, with the majority having sensitivity of ≥ 0.6, with the exceptions of atrial thrombi, atrial septal defect and PE. Thus screening may result in considerable FNs for atrial thrombi, atrial septal hypertrophy/defect and PE. In general, sensitivity was lower for atrial thrombi, atrial septal defect and PE than for other pathologies, and specificity was lower for aortic dissection and pulmonary disease than for other pathologies. TTE seems to be a sufficient diagnostic tool for most pathologies included here, but there may need to be extra screening for PE by lung scan, and atrial thrombi and atrial septal hypertrophy by TOE.

All studies had a high percentage of usable, good images from TTE. Although for some studies participants were selected on the basis of having usable TTE images, even for other studies the lowest percentage of usable images was 85%.

In practice, accuracy will depend on the skill of the echocardiographer. Studies of diagnostic accuracy used experienced echocardiographers. It may be that when less-experienced staff are employed, there is lower accuracy. Even with skilled echocardiographers, there may be interobserver variations in the interpretation of images.^{128,129–132}

Diagnostic accuracy studies identified were published from 1981 to 2009; with many relatively old studies included, it may be that imaging techniques and equipment have improved since then. This means that the review may underestimate the accuracy of TTE.

Prognostic studies indicated that LV dysfunction as diagnosed by TTE was associated with a significantly increased risk of thromboembolism, stroke or mortality. Increased LAD as assessed by TTE was associated with a significantly increased risk of thromboembolism or mortality; however, it was not significantly associated with stroke when assessed in 10-mm increments. Valvular abnormality carried a significantly increased risk of mortality. MR was not significantly associated with stroke or thromboembolism in two studies; however, two other studies suggested a significantly increased risk of thromboembolism with mild MR, in contrast with a significantly protective effect of severe MR against stroke. There was no significant association found between mitral annular calcification and thromboembolism, or between MVP and stroke. These findings are consistent with the report of Providencia et al.,¹³ published after the literature search was conducted, which found that TTE-diagnosed LV systolic function and LA area measurement may provide a valuable addition to CHADS₂ and CHA₂ DS₂-VASc scores.¹³

Prevalence studies were sought for AF populations, and were not found for all pathologies. Prevalence studies were found for atrial septal defect, atrial septal aneurysm, atrial thrombus, ventricular thrombus, ischaemic heart disease or thrombosis, valvular heart disease, cardiomyopathy and heart failure. The prevalence studies had relevance to the UK. Two of the prevalence studies had UK populations, although the most common setting for the prevalence studies was USA. The wide variations in prevalence rates for specific pathologies may be explained by the degree of heterogeneity in the studies considered in this review. The sources of dissimilarities stem from study designs, characteristics of patients studied and severity of illness (e.g. as assessed by CHADS₂ scores). Although in most instances the diagnostic criteria for assessing pathologies of interest were outlined, there was a lack of detail regarding the description of the assessor or observer variability. Many of the studies used TOE to diagnose pathologies, and inadequate reporting of observer variation in transoesophageal echocardiographic examinations has been noted in available literature.¹³³

There was a high prevalence (around 25–30%) of ischaemic heart disease, valvular heart disease and heart failure in patients with AF in the included prevalence studies. Cardiomyopathy prevalence was around 5%, and atrial septal defect had a prevalence of < 1%.

Studies of AF have reported characteristics of patients with AF, including prevalences of cardiac pathologies. This review found a prevalence study only for atrial septal defect, whereas prevalence of structural heart disease, of any type, thus encompassing many difference pathologies, has been reported in 46%¹⁰⁸ or 54%¹¹⁴ of patients with AF not experiencing thromboembolic event or LAA thrombus, respectively. Prevalence of ischaemic heart disease found in this review was broadly in line with other reports. Ischaemic heart disease has been reported in 25%¹¹³ or 12%,¹³⁴ and coronary disease in 22%,²⁸ 56% of 188 patients with short-term (< 48 hours) AF,¹¹⁷ or 32% of first-detected AF,⁵⁴ 34% paroxysmal AF,⁵⁴ 29%⁵⁴ persistent AF, 36%⁵⁴ permanent AF. Atrial thrombus has been found in 3% AF¹³⁵ or 12–20% in post-mortem studies of valvular AF,¹³⁶ LA thrombus in 14% of new-onset AF,¹³⁷ and LAA thrombus in 12% non-valvular AF or atrial flutter.¹³⁸ Results of thrombus prevalence studies within this review fell within these estimates. In the Scherr study¹²³ all patients with atrial flutter had a larger LAD (> 4.5 cm) than those patients without LA thrombi. It was also noted that the prevalence of LAA thrombi increased with increasing CHADS₂ score. Although the prevalence of LAA thrombi ranges between 0.3% and 1.4% for those with scores of 0 and 1, the prevalence of this pathology occurs in 5.3% of patients with a score of ≥ 2. Atrial septal aneurysm has been reported in 2%¹³⁹ and LV aneurysm in 1% (SPAF Investigators 1992¹¹⁰) of patients with AF. This review did not find studies that set out to assess prevalence of pulmonary disease in patients with AF; however, pulmonary disease has been reported in 6% of patients with AF.¹³⁴ According to the Framingham heart study,¹⁹ approximately one-third of women with AF and one-fifth of men with AF have valvular heart disease.¹⁹ Results of valvular heart disease prevalence studies within this review were broadly in line with other reported estimates. Valvular heart disease has been reported in 10% of asymptomatic patients with AF and 26% of symptomatic patients with AF,¹³⁴ 23% AF,¹⁴⁰ 21% of first-detected AF,⁵⁴ 19% paroxysmal AF, 24% persistent AF⁵⁴ and 40% permanent AF,⁵⁴ with a review estimate of up to 40% AF.¹⁴¹ Cardiomyopathy has been reported in 8% of first-detected AF,⁵⁴ 7% paroxysmal AF,⁵⁴ 13% persistent AF⁵⁴ and 16% permanent AF.⁵⁴ Dilated cardiomyopathy has been found in 11% AF²⁸ and 17% patients with short-term (< 48 hours) AF.¹¹⁷ Heart failure has been reported in 26% of first-detected AF,⁵⁴ 23% paroxysmal AF,⁵⁴ 35% persistent AF⁵⁴ and 49% permanent AF.⁵⁴ According to the Framingham heart study,¹⁹ approximately one-quarter of men and women with AF have heart failure,¹⁹ with up to 42% patients with AF developing CHF during their lifetime.¹⁴² CHF in AF study participants has been reported as 28%¹¹³ or 40%,¹²² similar to results of prevalence studies included in this review. This review did not find studies that set out to assess prevalence of aortic dissection in patients with AF; however, aortic dissection has been reported in 7% patients with AF.¹²²

Overall, diagnostic accuracy of TTE and prevalence of pathologies in patients with AF indicate that routine TTE following AF diagnosis would identify pathologies in many patients, particularly with regard to valvular heart disease, ischaemic heart disease and heart failure. TTE seems to be a sufficient diagnostic tool for screening most pathologies included in this review. For completeness of screening, extra testing for PE by lung scan, and for atrial thrombi and atrial septal hypertrophy by TOE, would reduce risk of FNs from TTE. However, it is unclear whether identifying these pathologies, in addition to the many diagnosed by TTE, would lead to improvement above that of TTE screening. In practice, some patients may have been diagnosed with a pathology prior to AF diagnosis. Patients may have more than one pathology in addition to AF. In practice, some diagnoses are likely to be checked with other diagnostic tools before treatment change, which will minimise the impact of FPs, although FPs may lead to some unnecessary diagnostic tests.