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42

The Utility of Handheld Echocardiography for EarlyDiagnosis of Rheumatic Heart Disease

Andrea Beaton, MD, Twalib Aliku, MD, Emmy Okello, MD, Sulaiman Lubega, MD, Robert McCarter, ScD,Peter Lwabi, MD, and Craig Sable, MD, Washington, District of Columbia; Kampala, Uganda

Background: Rheumatic heart disease (RHD) remains endemic in most of the developing world. Echocardiog-raphy has proved highly sensitive for early detection of RHD, but it remains too costly for most low-incomesettings. Handheld ultrasound machines used to perform handheld echocardiography (HAND) are both lessexpensive and more portable, possibly making them ideal screening tools. HAND has never been tested forthe early diagnosis of RHD. The aim of this study was to evaluate the performance of focusedHAND comparedwith focused standard portable echocardiography for the diagnosis of subclinical RHD.

Methods: HAND and standard portable echocardiography were performed on 125 Ugandan children, 41 withborderline or definite RHD, and 84 healthy controls. Imageswere blindly reviewed according to the 2012WorldHeart Federation guidelines.

Results: HAND was highly sensitive (90.2%) and specific (92.9%) for distinguishing between normal patientsand those with RHD, but it performed best with definite RHD. HAND overestimated mitral valve morphologicvalve abnormalities, being only 66.7% specific for anterior leaflet thickness > 3 mm and 79.0% specificfor restricted leaflet motion. False-negative results (n = 4) were due primarily to underestimation of mitralregurgitation length.

Conclusions: In this population, HAND was highly sensitive and specific for early detection of RHD. HANDfunctions best as a screening tool with confirmation of positive screening results by fully functional echocar-diographymachines. Technical advancesmay enable one-step RHD screening usingHAND. The performanceof HAND should be studied across diverse populations and in field tests before recommending it forwidespread screening. (J Am Soc Echocardiogr 2014;27:42-9.)

Keywords: Echocardiography, Handheld echocardiography, Rheumatic heart disease, Screening

Rheumatic heart disease (RHD) causes significant disability andpremature death in developing nations, despite its virtual eliminationin most of the developed world.1 RHD results from cumulativeexposure to streptococcal infections, which can lead to cardiac inflam-mation, scarring, and dysfunction.2 The disease is usually progressive,starting in midchildhood. However, data from developing nationsshow that most patients present as young adults, once symptomsbecome severe enough to result in cardiovascular limitations.3

Furthermore, up to 40% of these symptomatic young adults cannot

ion of Cardiology, Children’s National Medical Center, Washington,

mbia (A.B., R.M., C.S.); and Uganda Heart Institute, Mulago Hospital

pala, Uganda (T.A., E.O., S.L., P.L.).

as supported by Award Number UL1TR000075 from the National

ealth National Center for Advancing Translational Sciences. Its con-

ly the responsibility of the authors and do not necessarily represent

s of theNational Center for Advancing Translational Sciences or the

utes of Health.

sts: Andrea Beaton, MD, Children’s National Medical Center,

ardiology, 111 Michigan Avenue, Washington, DC 20010 (E-mail:

c.org).

6.00

4 by the American Society of Echocardiography.

rg/10.1016/j.echo.2013.09.013

recall an episode of acute rheumatic fever,4 casting doubt on thenotion that improved primary clinical recognition can significantlyreduce the global burden of disease.

Symptomatic presentation of RHD in resource-poor settings hasdismal outcomes.5 Cardiac surgery or catheterization is often notavailable, and even when offered, it is often cost prohibitive. Datafrom Africa suggest particularly poor outcomes, with an averageage of RHD-related death of 25.89 years.6 Outcomes are evenmore tragic for pregnant mothers, 34% of whom will die in theperipartum period.7 By contrast, patients who present with earlyRHD generally have good outcomes. Secondary prophylaxis, in theform of penicillin injections every 3 to 4 weeks to prevent recurrentstreptococcal infection, in these patients is of proven benefit. The bestprognosis is for those with mild disease, the majority of whom, withregular secondary prophylaxis, will have no detectable cardiac diseaseafter 10 years.2,8 The challenge, then, is how to effectively findpatients with early RHD.

Over the past decade, echocardiography has proved to be themostsensitive tool for early detection of RHD.9 The World HealthOrganization now supports early detection of RHD through echocar-diography in high-prevalence regions.10 For the first time, the WorldHeart Federation (WHF) has provided evidence-based guidelinesfor the echocardiographic diagnosis of RHD.11 These guidelines arespecifically designed to define the ‘‘minimum echocardiographiccriteria for the diagnosis of RHD’’11 and are meant for use with

Abbreviations

FCU = Focused cardiacultrasound

HAND = Handheldechocardiography

RHD = Rheumatic heart

disease

STAND = Standard portable

echocardiography

WHF = World Heart

Federation

Journal of the American Society of EchocardiographyVolume 27 Number 1

Beaton et al 43

patients who live in endemicareas, have no symptoms ofRHD, and have no histories ofacute rheumatic fever. TheWHF guidelines provide instruc-tions for the systematic assess-ment of the morphology andfunction of the mitral and aorticvalves through limited echocar-diographic evaluation. Theywere designed for use with astandard portable echocardio-graphic machine, capable of two-dimensional and color image

acquisition as well as continuous-wave Doppler imaging.Despite increasingly affordable standard portable echocardio-

graphic machines, however, the price remains too highfor practitioners in most RHD-endemic countries. Newly availablehandheld ultrasound machines could both reduce RHD screeningcosts and increase the reach of such initiatives to even the mostremote settings. These ultraportable handheld machines haveproved effective in many settings, including routine outpatient echo-cardiographic evaluation,12 inpatient cardiac consultation,13 andassessing left ventricular function in the acute care setting.14 Theyare simple to use and are able to produce two-dimensional andcolor images but do not currently have the spectral Doppler capabil-ities needed to fully implement the WHF criteria. Their sensitivityand specificity for RHD detection compared with standard portableechocardiography (STAND) have not been evaluated. The objectiveof this study was to determine the sensitivity and specificity of afocused echocardiographic evaluation performed with handheldechocardiography (HAND) compared with STAND for the detec-tion of RHD in Uganda, a known high-prevalence area.15 This isthe first systematic evaluation of HAND as a tool for early RHDdetection.

METHODS

Study Population

This prospective observational study included a sample of pairedechocardiograms in 125 patients. Participants included 60 patientspresenting for follow-up as part of the Ugandan RHD registry project(Uganda Heart Institute, Mulago Hospital Complex, Kampala,Uganda) and 65 asymptomatic Ugandan schoolchildren who tookpart in an echocardiography-based screening program at theirschool.15 Each participant underwent a focused echocardiographicexamination with STAND. Additionally, each patient underwent afocused echocardiographic examination with HAND. All studieswere recorded in a 2-week period in September 2012. Institutionalreview board approval was obtained from Makerere University andthe Children’s National Medical Center.

Echocardiographic Protocol

One pediatric cardiologist (A.B.) performed all echocardiographicexaminations. Handheld echocardiographic equipment (Vscan; GEMedical Systems, Milwaukee, WI) used a 1.7-MHz to 3.4-MHztransducer. This device provides two-dimensional and colorDoppler imaging on an integrated 3.5-inch display. Frame ratesranged from 25 to 30 Hz for black-and-white imaging and from 12

to 16 Hz for color Doppler. The device offers an image-based‘‘Auto-Cycle’’ function for the automatic detection of a full heart cyclebeginning with end-diastole. Standard portable echocardiographicequipment (Vivid-I; GE Medical Systems) used a 1.5-MHz to3.6-MHz transducer. Frame rates ranged from 25 to 35 Hz forblack-and-white imaging and from 12-18 Hz for color Doppler. ForSTAND, electrocardiography was used to detect two heartbeat loops.STAND was used as the gold standard. Grayscale and color Dopplerrecordings (parasternal long-axis and short-axis and apical four-chamber views) were acquired and stored digitally for later offlineassessment. In addition, STAND included continuous-waveDoppler recordings at the mitral and aortic valves (not available onthe handheld echocardiographic device).

Protocol for Blinding

Each imaging study was assigned a unique research identificationnumber, which could be used to link the imaging study to theresearch participant. A single expert reviewer (C.S.) interpretedall handheld and standard portable echocardiographic studies. Thereviewer was blinded to the corresponding echocardiographicexamination (either HAND or STAND), but it was not possible toblind the reviewer to the type of study (HAND or STAND), becauseinterpretation occurred on different platforms (Figure 1 shows thehandheld echocardiographic platform), each device has a character-istic standardized screen setup, and images were interpreted usingdifferent software packages.

Image Scoring and Interpretation

For analysis, images from the handheld echocardiographic studieswere interpreted using the dedicated Vscan Gateway softwareinstalled on a standard personal computer. The size of the imagewas slightly larger on the computer than on the handheld echocardio-graphic device, but the resolution of the images was identical. Imagesfrom the standard portable echocardiographic studies were trans-ferred to our institution’s echocardiographic picture archiving andcommunication system for interpretation. Studies were analyzed inrandom order. A score for image quality (ranging from 1 to 5, with5 being the best) was assigned to describe the quality of the overallimage, the quality of the mitral valve images, and the quality of theaortic valve images for all studies.

Echocardiographic interpretation of the standard portable echo-cardiographic studies was conducted according to the 2012 WHFguidelines (Table 1).11 Because of the lack of continuous-waveDoppler capabilities in the handheld echocardiographic studies,modified 2012 WHF criteria were used to determine pathologicregurgitation (Table 2). Overall categorization of disease presence(normal, borderline RHD, or definite RHD) was recorded, as wellas the individual morphologic and functional components used toarrive at this categorization.

Statistical Analysis

Study data were collected andmanaged using the REDCap electronicdata-capture tools hosted at the Children’s National MedicalCenter.16 Groups were compared using a one-way analysis of vari-ance for continuous data and c2 tests for categorical data.Sensitivity and specificity were calculated for overall RHD detection(combined definite RHD and borderline RHD), as well as separatelyfor definite and borderline RHD. Individual components composingthe 2012 WHF criteria were also examined.

Figure 1 Deidentified handheld echocardiographic parasternal long-axis images being analyzed with the Vscan Gateway softwarepackage on a personal computer. Black-and-white images show measurement of the thickness of the anterior mitral leaflet (limitedto 1-cm intervals), and color Doppler images show measurement of the mitral regurgitation jet length.

Table 1 WHF 2012 guidelines for echocardiographicdiagnosis of RHD (patients aged < 20 years)

Criterion

Definite RHD

A. Pathologic MR and at least two morphologic features of RHD of

the MV

B. MS mean gradient > 4 mm Hg*

C. Pathologic AR and at least two morphologic features of RHD ofthe AV†

D. Borderline disease of both the AV and MV‡

Borderline RHD

A. At least two morphologic features of RHD of the MV without

pathologic MR or MS

B. Pathologic MR

C. Pathologic AR

AR, Aortic regurgitation; AV, aortic valve; MR, mitral regurgitation;

MS, mitral stenosis; MV, mitral valve.

*Congenital MV anomalies must be excluded.†Bicuspid AV and dilated aortic root must be excluded.‡Combined AR and MR in high-prevalence regions and in the

absence of congenital heart disease is regarded as rheumatic.

Table 2 WHF 2012 guidelines for diagnosis of pathologicregurgitation

Pathologic MR Pathologic AR

2012 WHF criteriaSeen in two views Seen in two views

In at least one view, jet

length > 2 cm*

In at least one view, jet length > 1 cm*

Velocity > 3 m/sec for

one complete envelope

Velocity > 3 m/sec in early diastole

Pansystolic jet in at least

one envelope

Pandiastolic jet in at least one

envelope

Modified criteria†,‡

Seen in two views Seen in two views

In at least one view, jet

length > 2 cm*

In at least one view, jet length

> 1 cm*

Pansystolic jet (by color

Doppler)

Pandiastolic jet (by color Doppler)

AR, Aortic regurgitation; MR, mitral regurgitation.*Regurgitant jet length should be measured from the vena contracta

to the last pixel of regurgitant color (blue or red).†Exclusion of continuous-wave Doppler evaluation for determination

of pathologic versus nonpathologic valvular regurgitation.‡In this study, pathologic MR or AR was considered present in

patients meeting the above criteria.

44 Beaton et al Journal of the American Society of EchocardiographyJanuary 2014

RESULTS

Paired echocardiograms were available for interpretation on all 125Ugandan children. Of these children, 84 (67%) were found to benormal, 16 (13%) were found to have borderline RHD, and 25(20%) were found to have definite RHD by STAND. No childrenwere found to have congenital heart disease. Descriptive characteris-tics of these three populations are located in Table 3. The majority ofpatients with borderline and definite RHD had isolated mitral

valve disease, with seven patients havingmixed aortic andmitral valvedisease (28%) and only one patient (4%) having isolated aortic valvedisease. In addition, 12 patients (14%) found to be normal hadnonpathologic mitral regurgitation, while none had nonpathologicaortic regurgitation.

Table 3 Demographic and echocardiographiccharacteristics by diagnosis (STAND)

Variable

Normal

Borderline

RHD

Definite

RHD

P(n = 84) (n = 16) (n = 25)

Mean age (y) 10.7 11.1 11.1 .74Women 52.4% 62.5% 60% .66

MR (cm) 12 15 241.1–1.5 cm 6 0 0

1.6–1.9 6 1 32.0–2.5 0 13 3

>2.5 0 1 18MS 0 0 5

Morphologic MV abnormalities 7 7 24Anterior mitral leaflet

thickness > 3 mm

4 7 24

Chordal thickening 0 1 20Restricted leaflet motion 3 2 14

Excessive leaflet motion 0 0 10AR 0 0 8

>1 cm 0 0 8Morphologic AV abnormalities 0 0 6

Thickening 0 0 6Coaptation defect 0 0 5

Restricted leaflet motion 0 0 3Prolapse 0 0 4

AR, Aortic regurgitation; AV, aortic valve; MR, mitral regurgitation;

MS, mitral stenosis; MV, mitral valve.

Journal of the American Society of EchocardiographyVolume 27 Number 1

Beaton et al 45

Figures 2 and 3 (definite and borderline RHD, respectively)compare parasternal long-axis views obtained in two patients withRHD. Table 4 compares disease categorization by STAND andHAND. Table 5 lists the sensitivity and specificity of HAND in overallRHD diagnosis (definite and borderline RHD). For the overall distinc-tion between normal patients and those with RHD (borderline anddefinite), HAND performed well, with excellent sensitivity (90.2%)and specificity (92.9%). After elimination of those classified as havingdefinite RHD by STAND, HANDwas less sensitive for discriminatingbetween borderline and normal, at only 75%. To understand thereasons for disagreement between machines, the sensitivity andspecificity of the individual components of diagnosis were examined(Table 5).

Of the 84 patients graded as normal by STAND, HAND incor-rectly classified six as having borderline RHD. Only one of thesepatients was diagnosed with borderline B disease (isolated signifi-cant mitral regurgitation), with the length of the mitral regurgita-tion jet found to be 1.7 cm on STAND and 2.2 cm on HAND(with all other features of pathologic regurgitation true on bothmachines). The remaining five false-positive results were incor-rectly classified as borderline A (at least two morphologic changeswithout significant mitral regurgitation). Handheld echocardio-graphic images had poor specificity for both mitral valve thickness(66.7%) and restricted leaflet motion (79.0%); handheld echocar-diographic images were interpreted to show morphologic changesnot seen on STAND. The prevalence of excessive mitral valveanterior leaflet tip motion was too low to accurately interpretsensitivity and specificity and did not contribute to any changein diagnosis.

Of the 16 patients graded as having borderline RHD by STAND,HAND determined that four were normal, eight had borderlineRHD, and four had definite RHD. All four false-negative results re-sulted from handheld echocardiographic interpretation of nonsignif-icant mitral regurgitation. In four studies with false-negative results,the length of the mitral regurgitation jet was found to be <2 cm,and the duration of regurgitation was judged not to be pansystolic.These four borderline cases were among the mildest in the STANDgroup, with mitral regurgitation jet lengths between 2 and 2.2 cm(0.6–1.8 cm on HAND). Underdiagnosis of pathologic mitral regur-gitation was also seen in two of eight patients (25%) correctly iden-tified by HAND as having borderline RHD. For these two patients,borderline B standard portable echocardiographic studies were iden-tified as borderline A by HAND, with underestimation of mitralregurgitation length and (again) overestimation of morphologicabnormalities. Overdiagnosis of morphologic abnormalities onhandheld echocardiographic images was also seen in the borderlinegroup, four of whose patients were diagnosed with definite RHD.

Functional mitral valve changes were detected by HAND withmore precision than were morphologic abnormalities. Pathologic re-gurgitant length (>2 cm) was detected with sensitivity of 83.3% andspecificity of 100%. Lack of continuous-wave Doppler necessitatedsubjective grading of the timing of mitral regurgitation on the basisof color Doppler images. Sensitivity and specificity suffered signifi-cantly from this method, being only 76.9% and 68.8%, respectively,for the detection of pansystolic regurgitation.

STANDwas slightly better than HAND in both overall image qual-ity and in quality of imaging of the mitral valve (3.85 vs 3.7, P = .05,and 3.9 vs 3.8, P = .05). No difference between machines was notedfor the quality of aortic valve imaging (3.7 vs 3.6, P = .29).

DISCUSSION

In this study, a critical first step in the validation of HAND for RHDscreening, we report the results of 125 evaluations using bothstandard portable and handheld echocardiographic machines.Compared with a field screening study, we used a population withan artificially large number of RHD-positive patients (borderlineRHD and definite RHD), reducing the needed sample size (whichis in the range of 5,000 patients, assuming an RHD prevalence of2%). In addition, we strategically chose one blinded expert reviewerfor all studies, eliminating the confounder of multiple reviewers andfocusing our evaluation solely on current handheld echocardio-graphic capabilities. In this first study of using HAND for RHD detec-tion, we show that HAND is highly sensitive and specific for thedetection of RHD. However, HAND performs better for somecomponents of the 2012 WHF criteria compared with others andmay be best suited as a screening tool rather than for full-field imple-mentation of the WHF guidelines.

The aim of screening is to identify RHD in apparently healthyindividuals.17 A useful screening tool ideally should have high sensi-tivity to limit the number of false-negatives while maintaining highspecificity to limit the number of false-positives. Both are importantin applying echocardiography to RHD screening in resource-constrained settings. False-negatives will result in missed opportu-nities to prevent disease progression, costing not only lives butalso valuable health care funds devoted to treating advancedRHD down the road. Conversely, false-positives impose on individ-uals the cost and burden of unnecessary long-term penicillin pro-phylaxis and the potential stigma of a chronic disease diagnosis.

Figure 2 (A) Two-dimensional parasternal long-axis view of the mitral valve by STAND (left) and HAND (right) in the same patientwith definite RHD. Arrow indicates the thickened anterior mitral valve leaflet, demonstrating excessive leaflet motion. (B) Thesame patient and devices in color Doppler mode. Arrow indicates the origin and termination of the mitral regurgitation jet in bothimages. LA, Left atrium; LV, left ventricle.

46 Beaton et al Journal of the American Society of EchocardiographyJanuary 2014

And for society, false-positives may flood limited subspecialistresources with unneeded secondary evaluations.9 Given these con-siderations, we believe that HAND would need to be both highlysensitive and specific compared with STAND to justify its use inwidespread screening.

In our study, HAND met this goal. It proved 90.2% sensitive and92.9% specific for differentiating normal patients and those withdisease. It performed even better for those with definite disease:100% sensitive and 96% specific. These results are consistent withthe only reported use of HAND for the evaluation of mitral valvedisease; that study reported high sensitivity (96%) and specificity(96%) for detecting more than moderate mitral regurgitation.18

However, 75% to 90% of RHD detected through echocardiographicscreening meets criteria for borderline RHD,15,19-22 with trivial tomild mitral regurgitation, for which HAND was only 75% sensitiveand 92.9% specific.

There are many studies in the literature that highlight the use offocused cardiac ultrasound (FCU) for the detection of chamberenlargement, ventricular dysfunction, and pericardial fluid.Although it is tempting to consider our study as another example ofFCU, the recent American Society of Echocardiography guidelinesmake a clear distinction between the methodology in our study andFCU.23 FCU is defined as being an adjunct to physical examinationin specific clinical settings. Applying this terminology to our study(or any study based on WHF echocardiographic guidelines forRHD), which did not involve ultrasound as an adjunct to physicalexamination, would be inconsistent with the 2013 AmericanSociety of Echocardiography definition of FCU.

The only other study to feature HAND for RHD detection used afirst-generation machine (Optigo; Philips Medical Systems, Andover,MA). The study assessed the ability of briefly trained operators todiagnose RHD, compared with diagnoses made with previous echo-cardiograms obtained on standard, fully functional machines. Threefinal-year medical students, after 8 hours of focused training, eachexamined 45 patients, 14 of whom had rheumatic mitral valvedisease and 31 of whom were normal. The man age in this cohortrange from 55.8 to 59.5 years, and all 14 patients with RHD had atleast moderate mitral stenosis (n = 13), at least moderate mitralregurgitation (n = 8), or both (number not reported). Sensitivityfor ultrasound diagnosis of mitral regurgitation and mitral stenosiswas very poor (averages of 21% and 33% across students).Pooled sensitivity (81%) and specificity (95%) for diagnosingrheumatic valve disease was significantly better, which the authorsattributed to a training program that focused on normal and rheu-matic mitral morphology.24 Multiple confounding variables,including technical image acquisition, the inherent image qualityof the machine, and the experience of the students, make it difficultto draw many conclusions from this study. In addition, the advancedage and disease severity of the population make the conclusionsunlikely to apply to a screening population.

The current generation of handheld ultrasound devices has manylimitations that are important to consider. Interpretation of handheldechocardiographic images tended to overdiagnosemorphologic mitralvalve changes. Measurement of the thickness of the anteriormitral valve leaflet, in particular, performed poorly. Some of this errorlikely resulted from functional software limitations. Currently, the

Figure 3 (A) Two-dimensional parasternal long-axis view of the mitral valve by STAND (left) and HAND (right) in the same patientwith borderline RHD. Arrow indicates the thickened anterior mitral valve leaflet and restricted leaflet motion. (B) The same patientand devices in color Doppler mode. Arrow points to the origin and termination of the mitral regurgitation jet in both images, whichdoes not meet the cutoff of 2 cm in length. LA, Left atrium; LV, left ventricle.

Table 4 Comparison of HAND and STAND for diseasecategorization

Category

STAND

Normal (n = 84) Borderline (n = 16) Definite (n = 25)

HANDNormal (n = 82) 78 4 0

Borderline (n = 14) 6 8 0

Definite (n = 29) 0 4 25

Journal of the American Society of EchocardiographyVolume 27 Number 1

Beaton et al 47

handheld ultrasoundmachines used in this study are capable of only 1-mmmeasurement increments. Practically, this results inmeasurementsof 2.5 to 2.9 mm (normal according to the 2012 WHF criteria) beingmeasured at 3 mm, which meets the criteria for thickened.Additionally, in this study, measurements for handheld echocardio-graphic studies were made using offline software to analyze still-frame images. Although it is possible to complete these measurementsin real time on the device,we feel that the additional blur that can comefrom live images would only exacerbate this limitation.

Alone, this single overstatement would not cause the valve to belabeled as morphologically abnormal; handheld echocardiographicinterpretations, however, also tended to overdiagnose chordal thick-ening and restricted leaflet mobility. In theory, suboptimal frame ratescan cause an overestimation of valve and chordal thickness if theframe demonstrating maximal valve excursion is not obtained.Conversely, though not seen in our study, slower frame rates may

also underestimate morphologic changes, as subtle tethering of thevalve leaflet can also be difficult to detect. Together, overestimationof morphologic abnormalities decreased the machine’s specificity,resulting in the diagnosis of more disease, and more severe disease,compared with standard portable echocardiographic studies. Usedas a screening tool, not as a final diagnostic instrument, these overes-timations could be corrected during secondary evaluation, reducingthe number of initially false-positive patients who unnecessarilyreceive prophylaxis.

Frame rate is unlikely to be a contributing factor to differences in ourstudy, because the frame rates were only slightly higher for STAND.However, slower frame rates are even more important to considerwhen comparing color Doppler evaluation. Low color Doppler framerates can result in underestimation of color Doppler jet length if theframe of maximal color jet length is not obtained. Additionally, lowerframe rates could make subjective determination of pansystolic regur-gitation (needed in the absence of continuous-wave Doppler and elec-trocardiographic tracing) less accurate. This could have beencompounded in our study, in which the standard portable echocardio-graphic studies contained two heartbeat loops, whereas most of thehandheld studies contained one heartbeat loop.

Functional assessment of the mitral valve also proved to have somechallenges when interpreting handheld echocardiographic imaging.The cutoff of 2 cm for the length of mitral regurgitation had adequatesensitivity and specificity (83.3% and 100%, respectively). However,technical parameters on the ultrasound machine can also influencethe length of the regurgitant jet. These include gain, carrier frequency,color scale, filter settings, and frame rate, which, if low, may miss the

Table 5 Sensitivity and specificity of HAND for overall RHD diagnosis and for individual components of RHD diagnosis, usingSTAND as the gold standard

Diagnosis Prevalence (%) Sensitivity (%) Specificity (%)

RHD Positive 32.8 90.2 (75.9–96.8) 92.9 (84.5–97.0)Definite RHD 20.0 100 (83.4–100) 96.0 (89.5–98.7)

Borderline RHD 12.8 75.0 (47.4–91.7) 92.9 (84.5–94.0)

MV morphology

Anterior mitral leaflet thickness > 3 mm 59.2 71.6 (59.8–67.8) 66.7 (59.8–81.2)

Chordal thickening 16.8 95.2 (74.12–99.9) 90.4 (82.6–95.0)

Restricted leaflet motion 16.0 85.0 (61.1–96.0) 79.0 (69.8–86.1)

Excessive leaflet tip motion 8.0 60.0 (27.4–86.3) 99.1 (94.5–99.9)

MV functionMR seen in two views* 87.3 81.3 (66.9–90.6) 28.6 (5.1–69.7)

Jet length > 2 cm 28.8 83.3 (66.5–93.0) 100 (94.8–100)

Pansystolic* 70.9 76.9 (56.9–89.0) 68.8 (41.5–87.9)

MR, Mitral regurgitation; MV, mitral valve.

*Prevalence, sensitivity, and specificity only among those studies in which MR was present.

48 Beaton et al Journal of the American Society of EchocardiographyJanuary 2014

time point of maximal jet length, contributing to poor accuracy,reproducibility, and relevance of this parameter. Although the WHFguidelines give clear guidance on optimizing machine settings, thecurrent handheld machine only allows control of gain, limiting theuser’s ability to optimize image acquisition. Additionally, more severeregurgitant jets can be difficult to measure, because the flow isdisturbed and the distal end of the regurgitant jet is irregular in shape(Figure 2B). However, this difficultly is limited to more severe regur-gitant jets, and we do not feel that it is an important contributor todetermining if a regurgitant length is physiologic or pathologic (>2or <2 cm). Finally, lack of continuous-wave Doppler capabilities ledus to modify the WHF criteria, eliminating the criterion of velocity> 3 m/sec needed to diagnose significant mitral or aortic regurgita-tion. In this study, elimination of this criterion from the handheldechocardiographic examinations did not independently alter anydiagnostic classifications.

In addition to some limitations in the current handheld echocardio-graphic technology, there are also some limitations to the WHFguidelines.11 Although currently, we believe these guidelines to bethe best available for early detection of RHD, they represent a compi-lation of the best available evidence, as well as expert consensusopinion. These criteria are essential for the standardization of world-wide protocols for the diagnosis of latent RHD, but they are likely farfrom perfect. It is only through time and careful data collection andanalysis that these guidelines will be able to be refined, improvingtheir specificity for clinically significant RHD.

Currently, the WHF guidelines call for frame rates between 30 and60 Hz, on the basis of prior studies. The impact of using lower framerates on accurate image interpretation has not been studied. However,high frame rates are less of an issue in patients with lower heart rates.Most of the patients in our study (and likelymost school-aged children)had heart rates < 80 beats/min. Nonetheless, optimization of framerates is an important consideration in applying the WHF criteria.

We also remain cautious when interpreting the WHF recommen-dation for pathologic mitral regurgitation jet length of 2 cm, becauseregurgitant length is determinedmore by afterload than by regurgitantvolumes. Although the velocity of aortic or mitral regurgitationcertainly does not contribute to assessment of regurgitant severity, itis included in the WHF criteria to differentiate true mitral or aorticregurgitation from artifacts or closing volumes. Using jet length to

distinguish pathologic regurgitation from artifacts or closing volumesfor screening seems reasonable, but without defining loading condi-tions (preload, systolic blood pressure), it is less likely to be an accurateway to track disease progression or improvement.

Similarly, we wish to highlight that the velocity of the regurgitationjet does not reflect the severity of the regurgitation, only the pressuredrop across the incompetent valve. The requirement of regurgitantflow velocity > 3 m/sec is meant to differentiate true mitral or aorticregurgitation from artifacts or closing volumes and should not be usedto grade the severity of disease or to track change in disease severityover time. In turn, in our study, the elimination of this criterion fromthe 2012WHF guidelines for handheld echocardiographic interpreta-tion (given no continuous-wave Doppler capability on the handheldmachines) did not independently affect the sensitivity or specificity ofthis device.

Finally, the WHF criteria do not provide guidance for how tomeasure nonlinear regurgitant jets. Often, posteriorly directedmitral regurgitation (most commonly seen with RHD) will track alongthe atrial wall, changing alignment and often color as the flow axisrelative to the ultrasound beam changes from ‘‘toward’’ to ‘‘away.’’Color flow jets that are directed centrally into the left atrium alsotend to appear larger because they entrain red blood cells on all sidesof the jet. In contrast, eccentric jets that hug the left atrial wall cannotentrain blood on all sides and tend to appear smaller than central jetsof similar severity; the color jet assumes the shape of a spoon in threedimensions.25 Although most commonly seen with longer jets,reducing its importance in screening, it is also possible that shorterjets could be underestimated when they are eccentric and followthe curve of the atrial wall. Standardization of technique to measurethese jets will be important for consistent reporting.

Our study had several limitations. In our cohort, RHD was limitedto the mitral valve in all but a few patients, leaving us without asufficient basis to accurately determine the sensitivity and specificityof functional and morphologic changes in the aortic valve.Although this bias is representative of disease pattern in Ugandan chil-dren, it may vary across settings, making these results less generaliz-able. The percentage of borderline patients in our cohort was small,resulting in a wide confidence interval for sensitivity for borderlinedisease. Larger numbers will be needed to more precisely defineHAND’s ability to detect borderline disease, because these children

Journal of the American Society of EchocardiographyVolume 27 Number 1

Beaton et al 49

represent the largest group of those found through screening.Additionally, although the reviewer was blinded to all clinical infor-mation, the physician performing the screens did so consecutivelyand thus was not blinded to the clinical condition of the patientsbefore handheld echocardiographic screening. Theoretically,although standardized views were obtained, this may have intro-duced bias to image acquisition. Finally, the population screenedwas not representative of the general population, as almost half ofthe patients came from an RHD follow-up clinic. The reviewer wasaware of the high prevalence of RHD in this population, whichmay have caused bias toward reading more abnormalities.

CONCLUSIONS

HAND holds great promise as a tool in the global effort to controlRHD. With time, handheld ultrasound devices likely will increase infunctional capabilities, making full implementation of the 2012WHF guidelines possible. We emphasize that given current specifica-tions (1-mm measurement increments, lack of continuous-waveDoppler), HAND is more reasonably a tool for screening ratherthan for full implementation of the 2012 WHF guidelines.However, for a small trade-off in specificity, HAND could be appliedto diagnosis in settings where secondary evaluation is resourcelimited. Additionally, future studies should examine how tomaximizethe sensitivity and specificity of HAND, which may include modifica-tion of the WHF criteria.

It is likely that handheld ultrasound technology will continue toevolve. The second-generation Vscan has a threefold longer batterytime than the first-generation system. Future developments mightinclude even longer battery life, solar-powered systems, wireless(including 3G and 4G) transfer of images, wider angle of imaging,improved imaging quality and frame rate, high-frequency trans-ducers, and fuller functionality, including spectral Doppler. If thesetechnological advances can be made while maintaining affordability,HAND offers the promise of a highly portable, sensitive, andspecific tool for widespread RHD screening.

This study represents a crucial first step in assessing the utility ofHAND for RHD screening. More research is needed to fully under-stand the performance of HAND for borderline RHD and amongpatients with aortic valve involvement. Importantly, our data provideclear evidence that the next step, a large-scale cross-sectional field studycomparing HAND with STAND, is justified. Additionally, if HAND isultimately validated for RHD screening, it will be important to developand test educational modules for training primary health care workersin the use of HAND technology, as it is these in-country nonexpertswho will likely compose the workforce worldwide.

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