Background
Rheumatic heart disease (RHD) remains endemic in most of the developing world. Echocardiography has proved highly sensitive for early detection of RHD, but it remains too costly for most low-income settings. Handheld ultrasound machines used to perform handheld echocardiography (HAND) are both less expensive and more portable, possibly making them ideal screening tools. HAND has never been tested for the early diagnosis of RHD. The aim of this study was to evaluate the performance of focused HAND compared with focused standard portable echocardiography for the diagnosis of subclinical RHD.
Methods
HAND and standard portable echocardiography were performed on 125 Ugandan children, 41 with borderline or definite RHD, and 84 healthy controls. Images were blindly reviewed according to the 2012 World Heart Federation guidelines.
Results
HAND was highly sensitive (90.2%) and specific (92.9%) for distinguishing between normal patients and those with RHD, but it performed best with definite RHD. HAND overestimated mitral valve morphologic valve abnormalities, being only 66.7% specific for anterior leaflet thickness > 3 mm and 79.0% specific for restricted leaflet motion. False-negative results ( n = 4) were due primarily to underestimation of mitral regurgitation length.
Conclusions
In this population, HAND was highly sensitive and specific for early detection of RHD. HAND functions best as a screening tool with confirmation of positive screening results by fully functional echocardiography machines. Technical advances may enable one-step RHD screening using HAND. The performance of HAND should be studied across diverse populations and in field tests before recommending it for widespread screening.
Rheumatic heart disease (RHD) causes significant disability and premature death in developing nations, despite its virtual elimination in most of the developed world. RHD results from cumulative exposure to streptococcal infections, which can lead to cardiac inflammation, scarring, and dysfunction. The disease is usually progressive, starting in midchildhood. However, data from developing nations show that most patients present as young adults, once symptoms become severe enough to result in cardiovascular limitations. Furthermore, up to 40% of these symptomatic young adults cannot recall an episode of acute rheumatic fever, casting doubt on the notion that improved primary clinical recognition can significantly reduce the global burden of disease.
Symptomatic presentation of RHD in resource-poor settings has dismal outcomes. Cardiac surgery or catheterization is often not available, and even when offered, it is often cost prohibitive. Data from Africa suggest particularly poor outcomes, with an average age of RHD-related death of 25.89 years. Outcomes are even more tragic for pregnant mothers, 34% of whom will die in the peripartum period. By contrast, patients who present with early RHD generally have good outcomes. Secondary prophylaxis, in the form of penicillin injections every 3 to 4 weeks to prevent recurrent streptococcal infection, in these patients is of proven benefit. The best prognosis is for those with mild disease, the majority of whom, with regular secondary prophylaxis, will have no detectable cardiac disease after 10 years. The challenge, then, is how to effectively find patients with early RHD.
Over the past decade, echocardiography has proved to be the most sensitive tool for early detection of RHD. The World Health Organization now supports early detection of RHD through echocardiography in high-prevalence regions. For the first time, the World Heart Federation (WHF) has provided evidence-based guidelines for the echocardiographic diagnosis of RHD. These guidelines are specifically designed to define the “minimum echocardiographic criteria for the diagnosis of RHD” and are meant for use with patients who live in endemic areas, have no symptoms of RHD, and have no histories of acute rheumatic fever. The WHF guidelines provide instructions for the systematic assessment of the morphology and function of the mitral and aortic valves through limited echocardiographic evaluation. They were designed for use with a standard portable echocardiographic machine, capable of two-dimensional and color image acquisition as well as continuous-wave Doppler imaging.
Despite increasingly affordable standard portable echocardiographic machines, however, the price remains too high for practitioners in most RHD-endemic countries. Newly available handheld ultrasound machines could both reduce RHD screening costs and increase the reach of such initiatives to even the most remote settings. These ultraportable handheld machines have proved effective in many settings, including routine outpatient echocardiographic evaluation, inpatient cardiac consultation, and assessing left ventricular function in the acute care setting. They are simple to use and are able to produce two-dimensional and color images but do not currently have the spectral Doppler capabilities needed to fully implement the WHF criteria. Their sensitivity and specificity for RHD detection compared with standard portable echocardiography (STAND) have not been evaluated. The objective of this study was to determine the sensitivity and specificity of a focused echocardiographic evaluation performed with handheld echocardiography (HAND) compared with STAND for the detection of RHD in Uganda, a known high-prevalence area. This is the first systematic evaluation of HAND as a tool for early RHD detection.
Methods
Study Population
This prospective observational study included a sample of paired echocardiograms in 125 patients. Participants included 60 patients presenting 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 took part in an echocardiography-based screening program at their school. Each participant underwent a focused echocardiographic examination with STAND. Additionally, each patient underwent a focused echocardiographic examination with HAND. All studies were recorded in a 2-week period in September 2012. Institutional review board approval was obtained from Makerere University and the Children’s National Medical Center.
Echocardiographic Protocol
One pediatric cardiologist (A.B.) performed all echocardiographic examinations. Handheld echocardiographic equipment (Vscan; GE Medical Systems, Milwaukee, WI) used a 1.7-MHz to 3.4-MHz transducer. This device provides two-dimensional and color Doppler imaging on an integrated 3.5-inch display. Frame rates ranged 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 cycle beginning with end-diastole. Standard portable echocardiographic equipment (Vivid-I; GE Medical Systems) used a 1.5-MHz to 3.6-MHz transducer. Frame rates ranged from 25 to 35 Hz for black-and-white imaging and from 12-18 Hz for color Doppler. For STAND, electrocardiography was used to detect two heartbeat loops. STAND was used as the gold standard. Grayscale and color Doppler recordings (parasternal long-axis and short-axis and apical four-chamber views) were acquired and stored digitally for later offline assessment. In addition, STAND included continuous-wave Doppler recordings at the mitral and aortic valves (not available on the handheld echocardiographic device).
Protocol for Blinding
Each imaging study was assigned a unique research identification number, which could be used to link the imaging study to the research participant. A single expert reviewer (C.S.) interpreted all handheld and standard portable echocardiographic studies. The reviewer was blinded to the corresponding echocardiographic examination (either HAND or STAND), but it was not possible to blind the reviewer to the type of study (HAND or STAND), because interpretation occurred on different platforms ( Figure 1 shows the handheld echocardiographic platform), each device has a characteristic standardized screen setup, and images were interpreted using different software packages.
Image Scoring and Interpretation
For analysis, images from the handheld echocardiographic studies were interpreted using the dedicated Vscan Gateway software installed on a standard personal computer. The size of the image was slightly larger on the computer than on the handheld echocardiographic device, but the resolution of the images was identical. Images from the standard portable echocardiographic studies were transferred to our institution’s echocardiographic picture archiving and communication system for interpretation. Studies were analyzed in random order. A score for image quality (ranging from 1 to 5, with 5 being the best) was assigned to describe the quality of the overall image, the quality of the mitral valve images, and the quality of the aortic valve images for all studies.
Echocardiographic interpretation of the standard portable echocardiographic studies was conducted according to the 2012 WHF guidelines ( Table 1 ). Because of the lack of continuous-wave Doppler capabilities in the handheld echocardiographic studies, modified 2012 WHF criteria were used to determine pathologic regurgitation ( Table 2 ). Overall categorization of disease presence (normal, borderline RHD, or definite RHD) was recorded, as well as the individual morphologic and functional components used to arrive at this categorization.
| 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 of the 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 |
∗ 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.
| Pathologic MR | Pathologic AR |
|---|---|
| 2012 WHF 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 ∗ |
| 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) |
∗ 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.
Statistical Analysis
Study data were collected and managed using the REDCap electronic data-capture tools hosted at the Children’s National Medical Center. Groups were compared using a one-way analysis of variance for continuous data and χ 2 tests for categorical data. Sensitivity and specificity were calculated for overall RHD detection (combined definite RHD and borderline RHD), as well as separately for definite and borderline RHD. Individual components composing the 2012 WHF criteria were also examined.
Results
Paired echocardiograms were available for interpretation on all 125 Ugandan children. Of these children, 84 (67%) were found to be normal, 16 (13%) were found to have borderline RHD, and 25 (20%) were found to have definite RHD by STAND. No children were found to have congenital heart disease. Descriptive characteristics of these three populations are located in Table 3 . The majority of patients with borderline and definite RHD had isolated mitral valve disease, with seven patients having mixed aortic and mitral valve disease (28%) and only one patient (4%) having isolated aortic valve disease. In addition, 12 patients (14%) found to be normal had nonpathologic mitral regurgitation, while none had nonpathologic aortic regurgitation.
| Variable | Normal | Borderline RHD | Definite RHD | P |
|---|---|---|---|---|
| ( n = 84) | ( n = 16) | ( n = 25) | ||
| Mean age (y) | 10.7 | 11.1 | 11.1 | .74 |
| Women | 52.4% | 62.5% | 60% | .66 |
| MR (cm) | 12 | 15 | 24 | |
| 1.1–1.5 cm | 6 | 0 | 0 | |
| 1.6–1.9 | 6 | 1 | 3 | |
| 2.0–2.5 | 0 | 13 | 3 | |
| >2.5 | 0 | 1 | 18 | |
| MS | 0 | 0 | 5 | |
| Morphologic MV abnormalities | 7 | 7 | 24 | |
| Anterior mitral leaflet thickness > 3 mm | 4 | 7 | 24 | |
| Chordal thickening | 0 | 1 | 20 | |
| Restricted leaflet motion | 3 | 2 | 14 | |
| Excessive leaflet motion | 0 | 0 | 10 | |
| AR | 0 | 0 | 8 | |
| >1 cm | 0 | 0 | 8 | |
| Morphologic AV abnormalities | 0 | 0 | 6 | |
| Thickening | 0 | 0 | 6 | |
| Coaptation defect | 0 | 0 | 5 | |
| Restricted leaflet motion | 0 | 0 | 3 | |
| Prolapse | 0 | 0 | 4 |
Figures 2 and 3 (definite and borderline RHD, respectively) compare parasternal long-axis views obtained in two patients with RHD. Table 4 compares disease categorization by STAND and HAND. Table 5 lists the sensitivity and specificity of HAND in overall RHD diagnosis (definite and borderline RHD). For the overall distinction between normal patients and those with RHD (borderline and definite), HAND performed well, with excellent sensitivity (90.2%) and specificity (92.9%). After elimination of those classified as having definite RHD by STAND, HAND was less sensitive for discriminating between borderline and normal, at only 75%. To understand the reasons for disagreement between machines, the sensitivity and specificity of the individual components of diagnosis were examined ( Table 5 ).
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