Color-Flow Doppler Echocardiography in Adults

Number: 0008

Policy

1. Aetna considers color-flow Doppler echocardiography in adults medically necessary for the following indications:

   1. During excision of left atrial mass
   2. Evaluation of angina
   3. Evaluation of aortic diseases
   4. Evaluation of aortocoronary bypass grafts
   5. Evaluation of atrial fibrillation/flutter
   6. Ealuatiion of cardiac function after the Fontan procedure
   7. Evaluation of cardiac tamponade
   8. Evaluation of cardiomyopathy (including hypertrophic cardiomyopathy (formerly known as idiopathic hypertrophic subaortic stenosis)
   9. Evaluation of congestive heart failure
   10. Evaluation of dyspnea (shortness of breath)
   11. Evaluation of heart murmur
   12. Evaluation of pericardial effusion
   13. Evaluation of prosthetic valves
   14. Evaluation of pulmonary hypertension
   15. Evaluation of septal defects
   16. Evaluation of site of left-to-right or right-to-left shunts
   17. Evaluation of valvular diseases (including mitral regurgitation and severity of valve stenosis)
   18. Monitoring of individuals after repair of tetralogy of Fallot
   19. Monitoring of individuals receiving cardiotoxic chemotherapy.

2. Aetna considers color-flow Doppler echocardiography in adults experimental and investigational for all other indications (e.g., to guide catheter ablation in ventricular tachycardia) because its effectiveness for these indications has not been established.

Related CPBs

• CPB 0106 - Fetal Echocardiography and Magnetocardiography
• CPB 0382 - Intravascular Ultrasound

Background

This policy is based on guidelines on diagnostic echocardiography in adults from the American College of Cardiology (Cheitlin et al, 2003).

Echocardiography is an ultrasound technique for diagnosing cardiovascular disorders.  It is subdivided into M-mode, two-dimensional (2-D), spectral Doppler, color Doppler, contrast, and stress echocardiography (Beers and Berkow, 1999).

Echocardiography is usually performed by placing a transducer over the chest.  In transesophageal echocardiography, however, the transducer is placed at the tip of an endoscope that is inserted into the esophagus (Beers and Berkow, 1999).  Even smaller transducers can be placed on intravascular catheters, permitting intravascular recordings of vessel anatomy and blood flow.

Two-dimensional (or cross-sectional) echocardiography is the dominant echocardiographic technique (Beers and Berkow, 1999; Gottdiener et al, 2004).  It uses pulsed, reflected ultrasound to provide spatially correct real time tomographic images of the heart, which are recorded on videotape and resemble cineangiograms.  Two-dimensional echocardiography provides information about the cardiac chamber size, wall thickness, global and regional systolic function, and valvular and vascular structures.  B-mode imaging refers to cross-sectional 2-D images displayed without motion, and provides detail of static structures.

M-mode (or motion-mode) echocardiography creates a continuous 1-D graphic display, and is useful for measuring single dimensions of walls and chambers of the heart, which can be used to estimate chamber volumes and left ventricular mass (Beers and Berkow, 1999; Gottdiener et al, 2004).  M-mode echocardiography is performed by directing a stationary pulsed ultrasound beam at some portion of the heart. 

The Doppler technique uses reflections from moving red blood cells to characterize blood flow (Beers and Berkow, 1999; Gottdiener et al, 2004).  Spectral Doppler echocardiography uses ultrasound to record the velocity, direction, and type of blood flow in the cardiovascular system.  The spectral Doppler signal is displayed on a strip chart recorder or videotape. 

Stress echocardiography uses any combination of the above echocardiography modalities, before and during (or shortly after) a physical or pharmacological stress intervention (Beers and Berkow, 1999; Gottdiener et al, 2004).  Most commonly, a treadmill or exercise bicycle is used for stress echocardiography.  In patients who are unable to exercise, stress testing can be performed with pharmacological agents, such as dobutamine, that increased myocardial oxygen demand, or vasodilators that produce coronary steal.  These tests have utility primarily in the detection of myocardial ischemia and viability. 

Contrast echocardiography is an M-mode or 2-D echocardiographic examination during which contrast agents are administered via venous injection (Beers and Berkow, 1999; Gottdiener et al, 2004).  Venous contrast injections are used to enhance left ventricular endocardial borders and Doppler signals and to assess myocardial perfusion.

Color Doppler echocardiography is essentially 2-D Doppler echocardiography with flow encoded in color to show its direction (red is toward and blue is away from the transducer) (Beers and Berkow, 1999; Gottdiener et al, 2004).  In color flow mapping, blood flow velocity is measured along each sector line of a 2-D echocardiographic image and is displayed as color coded pixels.  Color flow Doppler is most useful for assessing valves for regurgitation and stenosis, detecting the presence of intracardiac shunts, and imaging blood flow in the heart.

Evidence-based guidelines from the American College of Cardiology, American Heart Association, and American Society of Echocardiography (Antman et al, 2003) outlined the accepted capabilities for Doppler echocardiography in the adult patient.  Specific indications were classified as relating to "anatomy-pathology" or to "function", and each potential indication was rated from "most helpful" to "not useful."  

Among indications related to anatomy-pathology, color Doppler was rated as most helpful for evaluating septal defects (Antman et al, 2003).  Color Doppler was considered not useful for all other indications related to anatomy-pathology: evaluation of chamber size, thickness of walls, relation of chambers, early closure of mitral valve, systolic anterior motion of mitral valve, left ventricular mass, left ventricular masses (tumor, clot, vegetation), masses in atria and right ventricle, anatomic valvular pathology, and pericardial effusion. 

Among functional indications, color Doppler was considered most useful for evaluating the site of right-to-left and left-to-right shunts (Antman et al, 2003).  Color Doppler was also considered useful for evaluating severity of valve stenosis and valve regurgitation and evaluation of prosthetic valves.  Color Doppler was also considered to be of some use in evaluating aortic diseases.  Color Doppler was considered not useful for assessment of global left ventricular systolic function (ejection fraction), evaluation of regional wall motion, measurement of right ventricular and pulmonary artery systolic pressures, measurement of left ventricular filling pressure, measurement of stroke volume and cardiac output, assessment of left ventricular diastolic function, and identifying ischemia and viable myocardium with exercise or pharmacological stress.

Nishimura et al (2011) examined the significance of measurement of stenosis by aliasing coronary flow (the MOSAIC method) for the detection of proximal left coronary stenosis in patients with unstable angina (UA) by means of transthoracic Doppler echocardiography.  Patients (n = 107) with UA were evaluated.  Proximal left coronary flow was sought in the short axis at the aortic root level using color Doppler guidance.  When detected coronary flow showed color aliasing, the color velocity range was gradually increased until color aliasing nearly disappeared.  Then, the color baseline was shifted until the color flow showed "isovelocity".  Proximal coronary flow was detected in 86 (80.4 %) of 107 patients.  In these 86 patients, an optimal cut-off value of isovelocity greater than or equal to 47.5 cm/second predicted significant coronary stenosis (percent diameter stenosis greater than or equal to 70 %) of the proximal left anterior descending (American Heart Association segment 6) or left main coronary artery with a sensitivity of 88 %, specificity of 97 %, positive predictive value of 98 %, and negative predictive value of 86 %.  In all 107 patients, the same cut-off value predicted significant coronary stenosis with a sensitivity of 78 %, specificity of 98 %, positive predictive value of 98 %, and negative predictive value of 81 %.  The authors concluded that the MOSAIC method may play a complementary role in expeditious risk stratification and decision making in patients with UA.

The American College of Radiology's Expert Panel on Cardiovascular Imaging (Ho et al, 2011) states that echocardiography using color flow Doppler is essential for evaluating blood flow as seen across an atrial defect or a ventricular septal defect or across a valve.  Assessment of the valves (sclerosis, fusion, estimation of valve gradients) and determination of right ventricular systolic pressure can usually be achieved.

An UpToDate review on "Catheter ablation for ventricular arrhythmias" (Ganz, 2012) states that "[i]ntracardiac echocardiography (ICE) with 2D and Doppler color flow imaging may be useful to guide mapping and ablation catheters and monitor morphologic changes after ablation".  The reference cited was the study by Ren et al (2002) that comprised only 4 patients with ventricular tachycardia.  Thus, there is currently insufficient evidence to support the use of color-flow Doppler echocardiography during ventricular tachycardia ablation.

An UpToDate review on “Principles of Doppler echocardiography” (Manning, 2013) states that “Color flow imaging is typically used in the screening and assessment of regurgitant flows.  It is also useful in the assessment of intracardiac shunts (e.g., atrial and ventricular septal defects) and pulmonary vein flow, and to assist in continuous wave Doppler alignment for tricuspid regurgitation velocities”.

Evaluation of Pericardial Effusion and Cardiac Tamponade

Miranda and Oh (2017) stated that effusive-constrictive pericarditis (ECP) corresponds to the coexistence of a hemodynamically significant pericardial effusion and decreased pericardial compliance.  The hallmark of ECP is the persistence of elevated right atrial pressure post-pericardiocentesis.  The prevalence of ECP appeared higher in tuberculous pericarditis and lower in idiopathic cases.  The diagnosis of ECP is traditionally based on invasive hemodynamics but the presence of echocardiographic features of constrictive pericarditis post-pericardiocentesisis can also identify ECP.  Data on the prognosis and optimal treatment of ECP are still limited.  Anti-inflammatory agents should be the 1st-line of treatment.  Pericardiectomy should be reserved for refractory cases.

Chalikias et al (2017) examined the prognostic value of echocardiographic tissue imaging markers in predicting tamponade among patients with large malignant pericardial effusion compared to routinely used echocardiographic signs.  A total of 96 consecutive patients with large malignant pericardial effusion, not in clinical cardiac tamponade, underwent an echocardiographic examination and were prospectively assessed for 1 month.  Clinically evident cardiac tamponade was considered as the study end-point.  The prognostic performance of tricuspid valve annular plane systolic excursion (TAPSE) and peak systolic annular velocity at the lateral margin of the tricuspid valve annulus (STV ) was assessed and compared to routinely used imaging signs.  During follow-up, 37 patients (39 %) developed clinically evident cardiac tamponade. TAPSE (area under the curve [AUC] 0.958) and STV (AUC 0.948) had excellent predictive accuracy for tamponade.  Multi-variate analysis showed that TAPSE (hazard ratio [HR] 3.03; 95 % confidence interval [CI]: 1.60 to 5.73, p = 0.001) and STV (HR 1.17; 95 % C: 1.05 to 1.29, p = 0.005) remained independent significant predictors of cardiac tamponade.  Re-classification analysis and decision curve analysis showed additive prognostic value and adjunct clinical benefit of these markers when added to a recently published triage pericardiocentesis score.  The authors concluded that echocardiographic tissue imaging markers such as TAPSE and STV are characterized by an excellent prognostic ability for development of cardiac tamponade and better prognostic value compared to routine echocardiographic signs in patients with large malignant pericardial effusion.  Incorporating these markers to a recent triage pericardiocentesis score resulted in additional prognostic value and increased clinical benefit.

Honasoge and Dubbs (2018) noted that one of the most common causes of pericardial effusion in the Western world is malignancy.  Emergency physicians must maintain vigilance in suspecting pericardial effusion and tamponade in patients with known or suspected malignancy who present with tachycardia, dyspnea, and hypotension.  Diagnosis can be expedited by key physical examination, electrocardiogram, and sonographic findings.  Unstable or crashing patients with tamponade must undergo emergent pericardiocentesis for removal of fluid and pressure to restore cardiac output.

Miranda et al (2019) reviewed 2D and Doppler findings in patients diagnosed with ECP and compared these to patients with cardiac tamponade and patients with surgically-proven constrictive pericarditis (CP).  These researchers identified 22 patients diagnosed with ECP at Mayo Clinic, MN between 2002 and 2016 who had persistent elevation of jugular venous pressure post-pericardiocentesis.  They compared them to 30 patients with CP and 30 patients with cardiac tamponade who had normalization of venous pressure post-pericardiocentesis.  All patients were in sinus rhythm.  Mean age was 57 ± 18 years in the ECP group; 36 % were women.  Most ECP and cardiac tamponade cases were idiopathic (41 % and 33 %, respectively).  Prior to pericardiocentesis, medial and lateral e' velocities were higher in ECP compared with tamponade; both ECP and tamponade patients had markedly decreased hepatic vein diastolic forward flow velocities.  Inspiratory and expiratory mitral E/A ratios were higher in ECP compared with tamponade, but lower than those observed in CP.  Post-pericardiocentesis, hepatic vein diastolic forward flow velocities increased in both ECP and tamponade.  Hepatic vein diastolic reversal velocities decreased in tamponade but were unchanged in ECP.  During median follow-up of 481 days, 3 patients required pericardiectomy for CP; they were all in the ECP group (14 % of ECP cases).  The authors concluded that ECP may have unique echo-Doppler features that distinguish it from both CP and tamponade.  These researchers stated that these findings suggested that ECP could be diagnosed by echocardiography even prior to pericardiocentesis; ECP appeared to have a good prognosis, particularly in patients presenting acutely.

An UpToDate review on “Cardiac tamponade” (Hoit, 2020) states that “Echocardiography -- Although cardiac tamponade is a clinical diagnosis, two-dimensional and Doppler echocardiography play major roles in the identification of pericardial effusion and in assessing its hemodynamic significance.  The use of echocardiography for the evaluation of all patients with suspected pericardial disease was highly recommended by a 2003 task force of the American College of Cardiology (ACC), the American Heart Association (AHA), and the American Society of Echocardiography (ASE).  The 2015 European Society of Cardiology (ESC) Guidelines recommend echocardiography as the initial imaging technique to assess the hemodynamic impact of a pericardial effusion and a judicious clinical evaluation that includes echocardiographic findings to guide the timing of pericardiocentesis.  In patients who do not have cardiac tamponade on initial assessment, but in whom the suspicion is high, repeat echocardiography during clinical follow-up may be appropriate to detect early signs of developing cardiac tamponade in the presence of large or rapidly accumulating effusions … Following either percutaneous or surgical drainage of a pericardial effusion in a patient with cardiac tamponade, the patient should be monitored with continuous telemetry and frequent vital signs for at least 24 to 48 hours.  Subsequent monitoring with two-dimensional and Doppler echocardiography prior to discharge from the hospital is warranted to confirm adequate fluid removal and to detect possible recurrent fluid accumulation”.

During Excision of Left Atrial Mass

Smith et al (1991) described the case of an asymptomatic patient who was discovered to have a large right atrial myxoma by transthoracic echocardiography.  Pre-operative considerations included the possibility of satellite lesions, left atrial origin, and a question of tricuspid valve involvement.  Subsequent operative transesophageal echocardiography demonstrated single-stalk attachment in the right atrial septal wall and no satellite lesions.  Doppler and color flow examination immediately following tumor removal aided in the decision not to perform tricuspid annuloplasty as there was no significant tricuspid regurgitation.  The authors concluded that the combined use of transthoracic and transesophageal echocardiography with Doppler and color flow imaging aids in the pre-operative and intra-operative diagnosis and surgical management of right atrial tumors.

Tekin et al (2019) stated that the treatment of atrial-extention Wilms’ tumor thrombus is surgical excision after chemotherapy.  Atriotomy with cardiovascular by-pass is the one of the most common method for this procedure.  These investigators presented a case of Wilms’ tumor with a tumor thrombus extending into the right atrium totally excised with retro-hepatic cavatomy.  A 3.5 year-old girl was admitted with the symptom of dysuria.  The examinations revealed a mass consistent with Wilms’ tumor in the middle and lower poles of the left kidney.  Doppler ultrasound (US) and echocardiographic examinations showed a tumor thrombus extending into the right atrium and some pulmonary nodules which were interpreted to be metastasis.  Wilms’ tumor was histopathologically diagnosed by an open biopsy.  After 3 courses of chemotherapy, imaging studies revealed that the atrial extention of the tumor thrombus persisted.  The tumor thrombus was found to be fibrotic on the magnetic resonance imaging (MRI) scan of the patient; thus, nephron-ureterectomy along with the excision of the tumor thrombus from the inferior vena cava was carried out with intra-operative continuous trans-esophageal echocardiography (TEE).  The suprarenal and retro-hepatic vena cava were exposed by dissecting and ligating all short hepatic veins and completely mobilizing the right lobe of the liver.  The thrombus was dissected out via vertical cavatomy at the retro-hepatic level.  TEE confirmed complete removal of the thrombus from the atrium; vena cava was then repaired.  There was no need for a blood transfusion, or cardiovascular by-pass (CBP) during the operation.  Total exposure of the retro-hepatic and sub-diaphragmatic vena cava using transplantation techniques was an effective method for the excision of a tumor thrombus without sternotomy, atriotomy and CBP, avoiding possible intra- and post-operative complications in selected cases of Wilms’ tumor with intra-atrial thrombus extension.  The case emphasized the importance of multi-disciplinary communication and collaboration.

Furthermore, an UpToDate review on “Echocardiographic evaluation of the atria and appendages” (Forster, 2021) states that “Although the left atrium and even the left atrial appendage can be imaged with transthoracic echocardiography, transesophageal echocardiography (TEE) permits detailed examination of most of the left atrium, including excellent views of the left atrial appendage.  TEE is the preferred approach for the detection of thrombi in the left atrium and appendage, given it is far more sensitive than transthoracic echocardiograph”.

Evaluation of Cardiac Function After the Fontan Procedure

Vitarelli et al (2005) noted that there is evidence that "inappropriate hypertrophy" of the single left ventricle, which occurs as a result of acute preload reduction, leads to adverse consequences on ventricular function.  However, a systematic study of the capability of tissue Doppler imaging (TDI) to examine systolic and diastolic ventricular functions after the Fontan procedure is still missing.  In a prospective study, a total of 24 post-operative patients aged 12 to 33 years were assessed with two-dimensional (2D) echocardiography equipped with TDI capabilities; 19 age-matched normal subjects were selected as controls.  Good-quality echoes for the measurement of ejection fractions (EFs) were available in 21 patients; 10 patients (group 1) had systolic dysfunction (EF less than 50 %), and 11 patients (group 2) had normal systolic function.  Peak systolic and diastolic wall velocities were acquired from the 2-chamber view in the myocardia and mitral annulus.  Compared with controls, the Fontan patients had a significantly reduced peak systolic velocity at wall and annulus sites.  A linear correlation existed between EF and systolic myocardial velocity from the annular sites.  Group 1 patients had lower wall velocities and lower annulus velocities both in systole and diastole.  Group 2 patients had preserved systolic velocities but decreased regional and annular early diastolic velocities, suggesting impaired filling.  Multiple correlation analysis showed a relation between peak early diastolic mitral velocity and ventricular EF, mean mitral annular motion at systole, mass/volume ratio, and the number of years post-Fontan revision.  The authors concluded that myocardial velocities recorded after the Fontan operation provided insight into systolic and diastolic ventricular functions.  The peak systolic mitral annular velocity correlated well with the ventricular EF.  The peak early diastolic velocity and the ratio between the early and late diastolic mitral annular velocity were reduced and reflected diastolic dysfunction even in the presence of normal systolic EF.

Stines et al (2011) stated that atrial function is increasingly being recognized as a significant factor in overall cardiac function in adults.  Limited studies evaluating atrial properties exist in the pediatric congenital heart disease population.  These researchers examined atrial properties in patients with single ventricle physiology after Fontan completion and compared these values with normal control patients. Echocardiography was carried out in patients with single ventricular physiology and in control patients; tissue Doppler and blood flow measurements were obtained.  Atrial fraction and atrial electromechanical values were calculated.  Differences were assessed with 1-way analysis of variance.  Post-hoc comparisons were carried out with Tukey adjustment; p < 0.05 was considered significant.  No significant difference was present in age or heart rate between single ventricle and control patients.  The single right ventricle tricuspid valve A wave (52.6 ± 14.5 versus 36.7 ± 10.4 cm/s) and atrial fraction (39.2 ± 6.2 versus 32.7 ± 7.7%) were significantly higher, and the E/A ratio (1.4 + 0.3 versus 1.8 + 0.4), tricuspid valve E/A velocity-time integral (1.6 + 0.4 versus 2.2 + 0.7 cm), and late diastolic annular value (5.3 + 1.5 versus 8.7 + 1.4 cm/s) were significantly lower compared with the controls.  The single left ventricle late diastolic annular velocity (4.2 + 1.0 versus 6.7 + 1.3 cm/s) was significantly lower and atrial fraction was significantly higher compared with the controls (37.7 ± 12.5 % versus 29.8 ± 4.3 %).  There were no significant differences in atrial electromechanical measurements between groups; however, the single right ventricle patients tended to have increased atrial dyssynchrony compared with controls.  The authors concluded that patients with single ventricle physiology after Fontan completion had differences in atrial properties when compared with normal controls.  These researchers stated that these differences may have important implications in their long-term outcomes; further studies are needed to determine the clinical significance of these findings.

Rios et al (2017) noted that quantitative echocardiographic measurements of single ventricular (SV) function have not been incorporated into routine clinical practice.  These investigators instituted a clinical protocol, which included quantitative measurements of SV deformation (global circumferential and longitudinal strain and strain rate), standard deviation of time to peak systolic strain, myocardial performance index (MPI), dP/dT from an atrioventricular valve regurgitant jet, and superior mesenteric artery resistance index, for all patients with a history of Fontan procedure undergoing echocardiography.   All measures were performed real time during clinically indicated studies and were included in clinical reports.  A total of 100 consecutive patients (mean age of 11.95 ± 6.8 years, range of  17 months to 31.3 years) completed the protocol between September 1, 2014 to April 29, 2015.  Deformation measures were completed in 100 % of the studies, MPI in 93 %, dP/dT in 55 %, and superior mesenteric artery Doppler in 82 %.  The studies were reviewed to evaluate for efficiency in completing the protocol.  The average time for image acquisition was 27.4 ± 8.8 mins (range of 10 to 62 mins).  The average time to perform deformation measures was 10.8 ± 5.5 mins (range of 5 to 35 mins) and time from beginning of imaging to report completion was 53.4 ± 13.7 mins (range of 27 to 107 mins).  There was excellent inter-observer reliability when deformation indices were blindly repeated.  Patients with a single left ventricle had significantly higher circumferential strain and strain rate, longitudinal strain and strain rate, and dP/dT compared to a single right ventricle.  There were no differences in quantitative indices of ventricular function between patients of less than 10 years versus of greater than 10 years post-Fontan.  The authors concluded that advanced quantitative assessment of SV function post-Fontan can be consistently and efficiently performed real time during clinically indicated echocardiography with excellent reliability.

Margossian et al (2016) noted that patients with functional single ventricles after the Fontan procedure have abnormal cardiac mechanics.  These researchers determined factors that influence diastolic function and described associations of diastolic function with current clinical status.  Echocardiograms were obtained as part of the Pediatric Heart Network Fontan Cross-Sectional Study.  Diastolic function grade (DFG) was assessed as normal (grade 0), impaired relaxation (grade 1), pseudonymization (grade 2), or restrictive (grade 3).  Studies were also classified dichotomously (restrictive pattern present or absent).  Relationships between DFG and pre-Fontan variables (e.g., ventricular morphology, age at Fontan, history of volume-unloading surgery) and current status (e.g., systolic function, valvar regurgitation, exercise performance) were examined.  DFG was calculable in 326 of 546 subjects (60 %) (mean age of 11.7 ± 3.3 years).  Overall, 32 % of patients had grade 0, 9 % grade 1, 37 % grade 2, and 22 % grade 3 diastolic function.  Although there was no association between ventricular morphology and DFG, there was an association between ventricular morphology and E', which was lowest in those with right ventricular morphology (p < 0.001); this association remained significant when using Z scores adjusted for age (p < 0.001).  DFG was associated with achieving maximal effort on exercise testing (p = 0.004); the majority (64 %) of those not achieving maximal effort had DFG 2 or 3.  No additional significant associations of DFG with laboratory or clinical measures were identified.  The authors concluded that assessment of diastolic function by current algorithms resulted in a high percentage of patients with abnormal DFG; however, few clinically or statistically significant associations were found.  This may imply a lack of impact of abnormal diastolic function on clinical outcomes in this cohort, or it may indicate that the methodology may not be applicable to pediatric patients with functional single ventricles.

Michel et al (2016) stated that accurate assessment of ventricular function is particularly important in children with hypoplastic left heart syndrome (HLHS) after completion of the total cavo-pulmonary connection (TCPC).  For this purpose, 2D speckle tracking (2DST) is a promising technique as it does not depend on the angle of insonation or the geometry of the ventricle.  These researchers examined changes in systolic and diastolic right ventricular (RV) function within a 5-year follow-up period of HLHS patients after Fontan palliation using conventional and 2DST echocardiography.  RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), E/A, E/e' and 2DST parameters [global longitudinal peak systolic strain (GS) and strain rate (GSRs), global strain rate in early (GSRe) and late (GSRa) diastole] of 40 HLHS patients were compared at 1.6 and at 5.1 years after TCPC.  RVFAC, E/A, E/e' and GS did not change, whereas TAPSE (13.7 ± 3.2 versus 10.5 ± 2.4 mm/m(2), p < 0.001), GSRs (-1.56 ± 0.28 versus -1.35 ± 0.31 1/s, p < 0.001), GSRe (2.22 ± 0.49 versus 1.96 ± 0.44 1/s, p = 0.004) and GSRa (1.19 ± 0.39 versus 0.92 ± 0.39 1/s, p < 0.001) decreased significantly.  Systolic and diastolic RV function parameters of HLHS patients decreased from 1.6 to 5.1 years after TCPC in these patients.  The authors concluded that changes in global strain rate parameters may be signaling early RV dysfunction that is not detectable by traditional echocardiography; further study is needed to verify this and to examine if these changes are clinically relevant.

Furthermore, an UpToDate review on “Overview of the management and prognosis of patients with Fontan circulation” (Johnson and Connolly, 2021) states that “Echocardiography may identify systemic ventricular dysfunction.  This is typically assessed using a combination of qualitative and quantitative measures.  Changes in ventricular function should prompt consideration for further evaluation (e.g., catheterization or advanced imaging) and addition of heart failure therapies.  Atrioventricular and semilunar valve disease are also assessed routinely by TTE, and the presence of severe valve disease may prompt further intervention.  Intracardiac thrombus is sought routinely, especially those with arrhythmias and/or atrio-pulmonary Fontan procedure with associated right atrial dilation.  Aortic dilation may be noted in select patient populations following Fontan procedure.  Echocardiography with Doppler and other imaging modalities may identify obstruction at any point in the Fontan circuit.  If suspected, cardiac catheterization will be required to confirm and determine best treatment options.  Since echocardiography and other imaging may miss Fontan obstruction, cardiac catheterization is the diagnostic test of choice when obstruction is suspected”.

Monitoring of Patients After Repair of Tetralogy of Fallot

An UpToDate review on “Management and outcome of tetralogy of Fallot” (Doyle et al, 2021) states that “Echocardiography is recommended annually until the age of 10 years and every 2 years through adulthood.  The focus of echocardiography monitoring is to:

• Detect the presence and size of any residual septal defects
• Determine the severity of pulmonary insufficiency
• Determine if there is persistent RVOT obstruction, and if present, ascertain the severity and the site of obstruction
• Assess RV and left ventricular size, function, and wall motion
• Detect any aortic root dilation and/or aortic valve insufficiency.

Monitoring of Patients Receiving Cardiotoxic Chemotherapy

Chemotherapy drugs that can cause irreversible toxicity include anthracyclines (daunorubicin, doxorubicin, epirubicin, idarubicin); alkylating agents (busulfan, carboplatin, carmustine, chlormethine, cisplatin, cyclophosphamide, mitomycin); taxanes (docetaxel, cabazitaxel, paclitaxel); topoisomerase inhibitors (etoposide, tretinoin, vinca alkaloids); and antimetabolites (cladribine, cytarabine, 5-FU). In addition, certain monoclonal antibodies (trastuzumab, bevacizumab) and tyrosine kinase inhibitors (e.g., lapatinib and sunitinib) have been associated with reversible cardiotoxicity (Thomas, 2017).

Thavendiranathan et al (2014) stated that the literature examining the utility of advanced echocardiographic techniques (such as deformation imaging) in the diagnosis and prognostication of patients receiving potentially cardiotoxic cancer therapy has involved relatively small trials in the research setting.  In a systematic review of the current literature, these investigators described echocardiographic myocardial deformation parameters in 1,504 patients during or after cancer chemotherapy for 3 clinically-relevant scenarios.  The systematic review was carried out following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the Embase (1974 to November 2013) and Medline (1946 to November 2013) databases.  All studies of early myocardial changes with chemotherapy demonstrated that alterations of myocardial deformation preceded significant change in left ventricular ejection fraction (LVEF) . Using tissue Doppler-based strain imaging, peak systolic longitudinal strain rate has most consistently detected early myocardial changes during therapy, whereas with speckle tracking echocardiography (STE), peak systolic global longitudinal strain (GLS) appeared to be the best measure.  A 10 % to 15 % early reduction in GLS by STE during therapy appeared to be the most useful parameter for the prediction of cardiotoxicity, defined as a drop in LVEF or heart failure (HF).  In late survivors of cancer, measures of global radial and circumferential strain are consistently abnormal, even in the context of normal LVEF, but their clinical value in predicting subsequent ventricular dysfunction or HF has not been explored.  The authors concluded that the findings of this systematic review confirmed the value of echocardiographic myocardial deformation parameters for the early detection of myocardial changes and prediction of cardiotoxicity in patients receiving cancer therapy.

Venturelli et al (2018) stated that cardiotoxic effects of anthracycline therapy are a major cause of morbidity for childhood cancer survivors.  In a retrospective study, these researchers examined the efficacy of tissue Doppler imaging (TDI) in the early detection of myocardial alterations in these patients.  A total of 50 childhood cancer survivors (32 males and 18 females) who have been treated with anthracyclines was evaluated by standard and TDI echocardiographic examination of the basal and median region of the interventricular septum (IVSb, IVSm), of the left ventricular posterior wall (LVPWb, LVPWm), and of the mitral annulus; the results were compared with those obtained from a population of 50 healthy age-matched and sex-matched controls by using the Student t-test.  The clinical and echocardiographic data of the 2 groups were compared also with the independent samples t-test.  All data were expressed as mean ± standard deviation.  A 2-tailed p-value of < 0.05 was considered statistically significant.  Statistical analysis was performed using STATA 7.0.  The case-control analysis showed statistically significant differences (p < 0,05) between the patients and the controls values.  The systolic performance of the patients was normal (LVEF (p = 0,0029) and LVFS (p = 0,0002)).  Statistically significant differences between patients and controls were found for diastolic function measurements obtained with PW Doppler such as IVRT (p = 0,0000), DT (p = 0,0041), E (p = 0,0000), A (p = 0,0458), even if E/A ratio was not altered.  TDI analysis also showed significant differences between patients and controls in both LVPW and IVS (basal and middle segments); E/E' ratio and E'/A' ratio did not vary significantly.  Linear Regression and multi-variate analysis showed that hematopoietic stem cell transplantation had the highest impact on the measurements.  The authors concluded that the results showed a myocardial diastolic impairment with preserved EF.  Since the median follow-up time of this cohort was 2 years, further evaluation is needed to better define the diastolic alterations.  These investigators stated that TDI analysis showed high sensitivity for the detection of mild myocardial dysfunction; the implementation of this novel method as standard practice in the follow-up of selected childhood cancer survivors might help to achieve a better management of long-term complications of cardiotoxic chemotherapy.

McGregor et al (2021) noted that transthoracic echocardiography is the primary cardiac imaging modality for the detection of cancer therapeutics-related cardiac dysfunction (CTRCD) through evaluation of serial changes in LVEF.  However, LVEF assessment by standard methods including 3D Echo has important limitations including the fact that reduction in LVEF occurs late in the process of CTRCD.  In contrast, by detecting early myocardial change, myocardial strain or deformation imaging has evolved to be a preferred parameter for detecting CTRCD.  Peak systolic GLS by STE has become an important pre-chemotherapy parameter that can independently predict subsequent adverse cardiac events as these abnormalities typically precede reduction in LVEF.  While an absolute GLS measurement may be informative, a 10 % to 15 % early reduction in GLS by STE appeared to be the most useful prognosticator for cardiotoxicity while on therapy.  These investigators presented a current systematic literature review of application of myocardial strain imaging in cancer patients performed following PRISMA guidelines using electronic databases from Medline, Embase, and SCOPUS Library from their inception until June 11, 2020.  This review demonstrated the incremental value of myocardial deformation imaging over traditional LVEF in detection and its clinical implication in management of CTRCD.

Furthermore, an UpToDate review on “Cardiotoxicity of non-anthracycline cancer chemotherapy agents” (Floyd and Morgan, 2021) states that “Trabectedin is an alkaloid that is approved for use in soft tissue sarcomas after progression on an anthracycline.  It has been associated with a low rate of cardiac toxicities, including congestive heart failure and rarely, cardiac arrest.  The median time to development of grade 3 to 4 cardiotoxicity on trabectedin is 5.3 months.  A baseline assessment of ejection fraction should be performed using echocardiogram or multi-gated acquisition (MUGA) prior to initiation of trabectedin and at 2- to 3-month intervals while treatment is continued.  Trabectedin should be held for a decrease in ejection fraction below the lower limit of normal and permanently discontinued for symptomatic cardiomyopathy or for persistent left ventricular dysfunction that does not recover to the lower limit of normal within 3 weeks”.

Appendix

Note on documentation requirements: Physicians are reminded to bill the findings of the diagnostic test as the primary indication rather than the referring physician’s diagnosis, as indicated by Medicare’s Diagnostic Imaging Billing guidelines.  These guidelines are available in the Medicare Claims Processing Manual, Chapter 13 - Radiology Services and Other Diagnostic Procedures (revised November 2016).  This is also indicated in the ICD-9-CM Coding Guidelines, Section IV, Paragraph L. 

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered if selection criteria are met:
+ 93325	Doppler echocardiography color flow velocity mapping (List separately in addition to codes for echocardiography)
Other CPT codes related to the CPB [parent codes for 93325]:
33615	Repair of complex cardiac anomalies (eg, tricuspid atresia) by closure of atrial septal defect and anastomosis of atria or vena cava to pulmonary artery (simple Fontan procedure)
33617	Repair of complex cardiac anomalies (eg, single ventricle) by modified Fontan procedure
75561	Cardiac magnetic resonance imaging for morphology and function without contrast material(s), followed by contrast material(s) and further sequences
76825	Echocardiography, fetal, cardiovascular system, real time with image documentation (2D), with or without M-mode recording;
76826	follow-up or repeat study
76827	Doppler echocardiography, fetal, pulsed wave and/or continuous wave with spectral display; complete
76828	follow-up or repeat study
93303	Transthoracic echocardiography for congenital cardiac anomalies; complete
93304	follow-up or repeat study
93306	Echocardiography, transthoracic, real-time with image documentation (2D), includes M-mode recording, when performed, complete, with spectral Doppler echocardiography, and with color flow Doppler echocardiography
93308	Echocardiography, transthoracic, real-time with image documentation (2D), includes M-mode recording, when performed, follow-up or limited study
93312	Echocardiography, transesophageal, real time with image documentation (2D) (with or without M-mode recording); including probe placement, image acquisition, interpretation and report
93314	image acquisition, interpretation and report only
93315	Transesophageal echocardiography for congenital cardiac anomalies; including probe placement, image acquisition, interpretation and report
93317	image acquisition, interpretation and report only
+ 93320	Doppler echocardiography, pulsed wave and/or continuous wave with spectral display (List separately in addition to codes for echocardiographic imaging); complete
+ 93321	follow-up or limited study (List separately in addition to codes for echocardiographic imaging)
93350	Echocardiography, transthoracic, real-time with image documentation (2D), includes M-mode recording, when performed, during rest and cardiovascular stress test using treadmill, bicycle exercise and/or pharmacologically induced stress, with interpretation and report
93351	including performance of continuous electrocardiographic monitoring, with physician supervision
93650	Intracardiac catheter ablation of atrioventricular node function, atrioventricular conduction for creation of complete heart block, with or without temporary pacemaker placement [experimental and investigational to guide catheter ablation procedures in ventricular tachycardia]
93653	Comprehensive electrophysiologic evaluation including insertion and repositioning of multiple electrode catheters with induction or attempted induction of an arrhythmia with right atrial pacing and recording, right ventricular pacing and recording (when necessary), and His bundle recording (when necessary) with intracardiac catheter ablation of arrhythmogenic focus; with treatment of supraventricular tachycardia by ablation of fast or slow atrioventricular pathway, accessory atrioventricular connection, cavo-tricuspid isthmus or other single atrial focus or source of atrial re-entry [experimental and investigational to guide catheter ablation procedures in ventricular tachycardia]
93654	Comprehensive electrophysiologic evaluation including insertion and repositioning of multiple electrode catheters with induction or attempted induction of an arrhythmia with right atrial pacing and recording, right ventricular pacing and recording (when necessary), and His bundle recording (when necessary) with intracardiac catheter ablation of arrhythmogenic focus; with treatment of ventricular tachycardia or focus of ventricular ectopy including intracardiac electrophysiologic 3D mapping, when performed, and left ventricular pacing and recording, when performed [experimental and investigational to guide catheter ablation procedures in ventricular tachycardia]
Other HCPCS codes related to the CPB:
C1886	Catheter, extravascular tissue ablation, any modality (insertable) [experimental and investigational to guide catheter ablation procedures in ventricular tachycardia]
ICD-10 codes covered if selection criteria are met:
A40.0 - A40.9	Streptococcal sepsis
A41.01 - A41.02	Sepsis due to staphylococcus aureus
A41.1 - A41.2	Sepsis due to other specified and unspecified staphylococcus
A41.3	Sepsis due to Hemophilus influenzae
A41.4	Sepsis due to anaerobes
A41.50	Gram-negative sepsis, unspecified
A41.51	Sepsis due to Escherichia coli [E. coli]
A41.52	Septicemia due to Pseudomonas
A41.53	Sepsis due to Serratia
A52.03	Syphilitic endocarditis
A54.83	Gonococcal heart infection
B39.4 (must be billed with I32)	Histoplasmosis capsulati (pericarditis)
B39.4 (must be billed with I39)	Histoplasmosis capsulati (endocarditis)
C38.0	Malignant neoplasm of heart [left atrial mass]
D15.1	Benign neoplasm of heart [left atrial mass]
I01.1	Acute rheumatic endocarditis
I01.2	Acute rheumatic myocarditis
I01.8	Other acute rheumatic heart disease
I01.9	Acute rheumatic heart disease, unspecified
I02.0	Rheumatic chorea with heart involvement
I05.0 - I05.9	Diseases of mitral valve
I06.0 - I06.9	Diseases of aortic valve
I07.0 - I07.9	Rheumatic tricuspid valve diseases
I08.0	Rheumatic disorders of both mitral and aortic valves
I09.0 - I09.89	Other rheumatic heart disease
I20.0 - I20.9	Angina pectoris
I21.01 - I22.9	Acute myocardial infarction
I21.A1	Myocardial infarction type 2
I21.A9	Other myocardial infarction type
I25.3	Aneurysm of heart
I26.09	Acute cor pulmonale
I27.0 - I27.2	Primary and other secondary pulmonary hypertension
I31.31, I31.39	Pericardial effusion (noninflammatory)
I31.4	Cardiac tamponade
I33.0 - I33.9	Acute and subacute endocarditis
I34.0 - 34.9	Nonrheumatic mitral valve disorders [valve regurgitation]
I35.0 - I35.9	Nonrheumatic aortic valve disorders [valve regurgitation]
I36.0 - I36.9	Nonrheumatic tricuspid valve disorders [valve regurgitation]
I37.0 - I37.9	Nonrheumatic pulmonary valve disorders
I38 - I39	Endocarditis and heart valve disorders
I40.0 - I40.9	Acute myocarditis
I42.0 - I43	Cardiomyopathy
I48.0 - I48.92	Atrial fibrillation and flutter
I50.0 - I50.9	Heart failure
I51.0	Cardiac septal defect, acquired
I51.1	Rupture of chordae tendineae, not elsewhere classified
I51.2	Rupture of papillary muscle, not elsewhere classified
I51.4	Myocarditis, unspecified
I51.7	Cardiomegaly
I51.81	Takotsubo syndrome
I51.89	Other ill-defined heart diseases
I71.00 - I71.9	Aortic aneurysm and dissection
I95.0 - I95.9	Hypotension
J81.0	Acute pulmonary edema
M31.4	Aortic arch syndrome [Takayasu]
O24.011 - O24.019, O24.111 - O24.119 O24.311 - O24.319, O24.811 - O24.819 O24.911 - O24.919	Diabetes mellitus in pregnancy
O33.6xx+	Maternal care for disproportion due to hydrocephalic fetus
O35.00x+	Maternal care for (suspected) central nervous system malformation in fetus
O35.10x+	Maternal care for (suspected) chromosomal abnormality in fetus
O35.2xx+	Maternal care for (suspected) hereditary disease in fetus
O35.3xx+	Maternal care for (suspected) damage to fetus from viral disease in mother
O35.4xx+	Maternal care for (suspected) damage to fetus from alcohol
O35.5xx+	Maternal care for (suspected) damage to fetus by drugs
O35.8xx+	Maternal care for other (suspected) fetal abnormality and damage
O35.9xx+	Maternal care for (suspected) fetal abnormality and damage, unspecified
O35.AXX0, O35.AXX1, O35.AXX2, O35.AXX3, O35.AXX4, O35.AXX5, O35.AXX9, O35.BXX0, O35.BXX1, O35.BXX2, O35.BXX3, O35.BXX4, O35.BXX5, O35.BXX9, O35.CXX0, O35.CXX1, O35.CXX2, O35.CXX3, O35.CXX4, O35.CXX5, O35.CXX9, O35.DXX0, O35.DXX1, O35.DXX2, O35.DXX3, O35.DXX4, O35.DXX5, O35.DXX9, O35.EXX0, O35.EXX1, O35.EXX2, O35.EXX3, O35.EXX4, O35.EXX5, O35.EXX9, O35.FXX0, O35.FXX1, O35.FXX2, O35.FXX3, O35.FXX4, O35.FXX5, O35.FXX9, O35.GXX0, O35.GXX1, O35.GXX2, O35.GXX3, O35.GXX4, O35.GXX5, O35.GXX9, O35.HXX0, O35.HXX1, O35.HXX2, O35.HXX3, O35.HXX4, O35.HXX5, O35.HXX9	Maternal care for other (suspected) fetal abnormality and damage
O36.0110 - O36.0999	Maternal care for rhesus isoimmunizations
O36.1110 - O36.1999	Maternal care for other isoimmunization
O40.1xx+ - O40.9xx+	Polyhydramnios
O43.011 - O43.019	Fetomaternal placental transfusion syndrome
O76	Abnormality in fetal heart rate and rhythm complicating labor and delivery
O98.511 - O98.519	Other viral diseases complicating pregnancy
O98.811 - O98.819	Other maternal infectious and parasitic diseases complicating pregnancy, childbirth and the puerperium
O98.911 - O98.919	Unspecified maternal infectious and parasitic diseases complicating pregnancy
O99.411 - O99.43	Diseases of the circulatory system complicating pregnancy, childbirth and puerperium
P02.3	Newborn (suspected to be) affected by placental transfusion syndrome
P03.810	Newborn affected by abnormality in fetal (intrauterine) heart rate or rhythm before the onset of labor
P03.819	Newborn affected by abnormality in fetal (intrauterine) heart rate or rhythm, unspecified as to time of onset
P04.11 - P04.19	Newborn affected by noxious substances transmitted via placenta or breast milk
P04.1A	Newborn affected by maternal use of anxiolytics
P04.3	Newborn affected by maternal use of alcohol
P04.40 - P04.49	Newborn affected by maternal use of drugs of addiction
P29.30 - P29.38	Persistent fetal circulation
P70.0 - P70.1	Syndrome of infant of mother with diabetes/gestational diabetes
P83.2	Hydrops fetalis not due to hemolytic disease
Q20.0 - Q21.9	Congenital malformations of cardiac chambers, connections and septa
Q22.0 - Q22.3	Congenital malformations of pulmonary valves
Q22.4	Congenital tricuspid stenosis
Q22.5	Ebstein's anomaly
Q23.0	Congenital stenosis of aortic valve
Q23.1	Congenital insufficiency of aortic valve
Q23.2	Congenital mitral stenosis
Q23.3	Congenital mitral insufficiency
Q23.4	Hypoplastic left heart syndrome
Q24.2	Cor triatriatum
Q24.3	Pulmonary infundibular stenosis
Q24.4	Congenital subaortic stenosis
Q24.8	Other specified congenital malformations of heart
Q26.0 - Q26.9	Congenital malformations of great veins
Q86.0	Fetal alcohol syndrome (dysmorphic)
Q87.40 - Q87.43	Marfan's syndrome
R01.1	Cardiac murmur, unspecified
R06.0	Dyspnea
R06.02	Shortness of breath
T82.01x+ - T82.09x+	Mechanical complication of heart valve prosthesis
T82.211+ - T82.218+	Mechanical complication of coronary bypass graft
T82.6xx+, T82.7xx+	Infection and inflammatory reaction due to cardiac valve prosthesis, vascular devices, implants, and grafts
T82.817+ - T82.9xx+	Other complications due to heart valve prosthesis
T86.20 - T86. 298	Complications of heart transplant
Z51.11	Encounter for antineoplastic chemotherapy
Z87.74	Personal history of (corrected) congenital malformations of heart and circulatory system
Z92.21	Personal history of antineoplastic chemotherapy
Z95.1	Presence of aortocoronary bypass graft
Z95.2	Presence of prosthetic heart valve
Z95.3	Presence of xenogenic heart valve
ICD-10 codes not covered for indications listed in the CPB:
I47.20, I47.21, I47.29	Ventricular tachycardia

The above policy is based on the following references: