Compliance with the provisions in this LCD may be monitored and addressed
through post payment data analysis and subsequent medical review audits.  
  
 **History/Background and/or General Information  
  
** Noninvasive testing in the outpatient setting to assess for coronary artery
disease (CAD) and left ventricular (LV) dysfunction may be accomplished by
utilizing conventional exercise stress testing without imaging or by utilizing
exercise or pharmacologic stress testing with imaging.  
  
Cardiovascular stress testing, also referred to as exercise stress test (EST),
exercise electrocardiogram, exercise treadmill test (ETT), graded exercise
test, or stress electrocardiogram (ECG), is used to provide information about
how the heart responds to exertion.  
  
Types of stress testing with imaging addressed in this LCD include stress
echocardiography, single photon emission computed tomography (SPECT)
myocardial perfusion imaging (MPI), positron emission tomography (PET) MPI,
and cardiac magnetic resonance imaging (CMR). Stress testing with imaging can
be performed with maximal exercise or chemical stress (dipyridamole,
dobutamine, adenosine, regadenoson, or other provocative agents).1,2  
  
Stress echocardiography, SPECT MPI, PET MPI and CMR are considered equivalent
diagnostic tests. However, in addition to myocardial ischemia, stress
echocardiography can provide information that is not obtainable with MPI, such
as valve function, assessment of pulmonary pressure, and assessment of dynamic
obstruction. The most commonly performed myocardial perfusion imaging are
single (at rest or stress) and multiple (at rest and stress) SPECT studies.
The CMR can also distinguish scar from hibernating myocardium, provide
information about valvular function, the presence of myocardial fibrosis, the
presence of morphological abnormalities, and provide an assessment of dynamic
obstruction without radiation exposure. This is especially valuable in
patients in whom good quality echocardiography images could not be obtained
due to technically difficult acoustic windows.3,4  
  
In many instances, EST may be combined with imaging procedures, such as MPI,
echocardiography, or other imaging procedures.  
  
A pharmacologic stress test may be performed when patients are unable to
exercise. This test involves the administration of a medication that is
designed to make the heart respond as if the patient was exercising. The
pharmacologic testing allows the provider to determine how the heart responds
to stress in the absence of exercise.  
  
Imaging of myocardial perfusion can also be combined with myocardial
metabolism imaging with fluorodeoxyglucose (F-18 FDG) for the assessment of
myocardial viability in areas of resting hypoperfusion and dysfunctional
myocardium. The stress protocols are, for the most part, similar for all
cardiac PET perfusion agents. The specific differences in acquisition
protocols for rubidium (Rb-82) and ammonia N-13 are related to the duration of
uptake and clearance of these radiopharmaceuticals and their physical half-
lives.  
  

**Covered Indications**  
  
 **Stress testing without cardiac imaging will be considered medically
reasonable and necessary for:**

  1. Patients with low or intermediate pre-test probability for CAD who are exhibiting cardiac symptoms, including otherwise unexplained angina equivalent symptoms with normal or minor changes in resting ECG and no contraindications to exercise.5-10
  2. Patients with diabetes mellitus who are exhibiting cardiac symptoms, including otherwise unexplained angina equivalent symptoms, with normal or minor changes in resting ECG and no contraindications to exercise.11
  3. New-onset atrial fibrillation (with no prior cardiac evaluation).10,12,13
  4. Determining functional capacity and response to therapy in patients with hypertrophic cardiomyopathy (HCM).14
  5. Patients with an intermediate or high CHD risk (ATP III risk criteria) who have experienced syncope (an abrupt, transient, complete loss of consciousness) and cardiac etiology is suspected based on an initial evaluation, including history, physical examination, or ECG and the patient is able to exercise.6,8,10,15,16
  6. Patients without cardiac symptoms who underwent a percutaneous coronary intervention (PCI) (with a stent) procedure more than 2 years prior or a coronary artery bypass graft (CABG) more than 5 years prior and have not undergone an evaluation for CAD within the past 2 years (stress echocardiogram, SPECT MPI, PET MPI, CMR, coronary computed tomography angiography [CCTA], cardiac catheterization) and are able to exercise.6,7,8,15,17,18
  7. Patients with established CAD who experienced an acute coronary syndrome (ACS) event (ST segment elevation myocardial infarction [STEMI], a Non-ST segment elevation myocardial infarction [NSTEMI], or unstable angina) within the past 90 days provided that they did not undergo coronary angiography at the time of the acute event and are currently clinically stable and able to exercise.6,8
  8. Patients with disease conditions associated with CAD (e.g., atherosclerotic abdominal aortic aneurysm, peripheral vascular disease, carotid artery disease, chronic renal failure) with no stress testing evaluation performed within the preceding 2 years and who are able to exercise.5,7,10,17
  9. Pre-operative cardiac evaluation in patients able to exercise and who will be undergoing noncardiac surgery with one of the following19:  

    * Intermediate risk for surgery (cardiac risk 1-5%), unknown functional capacity, and the results will affect patient management decisions.
    * High risk for surgery (> 5% cardiac risk), unknown functional capacity, and the results will affect patient management decisions.

**  
Stress testing with cardiac imaging will be considered medically reasonable
and necessary for:**  
  

  1. Patients experiencing new, recurrent, or worsening cardiac symptoms, including otherwise unexplained angina equivalent symptoms, **AND** any of the following:

  * Physical inability to perform a maximum exercise workload2,5,6,8-10,15,20; **OR  
  
**

  * New or previously unrecognized uninterpretable ECG2,5,6,8-10 **OR** ;

        * ECG is uninterpretable for ischemia due to **any one** of the following2,5,8,9,15,21:  
  

          * Complete left bundle branch block (right bundle branch does **not** render ECG uninterpretable for ischemia),21  
  

          * Ventricular paced rhythm,  
  

          * Pre-excitation pattern such as Wolff-Parkinson-White,  
  

          * A > 1 mm ST segment depression (NOT nonspecific ST/T wave changes),  
  

          * Left ventricular hypertrophy (LVH) with repolarization abnormalities, also called LVH with strain (NOT without repolarization abnormalities or by voltage criteria), **or  
  
**

          * Patient on digoxin therapy.  
  

      * A history of CAD based on a prior anatomic evaluation of the coronary arteries OR a history of CABG or PCI;6,8,15 **OR  
  
**

      * Syncope and collapse (an abrupt, transient, complete loss of consciousness) for patients with an intermediate or high CHD risk (ATP III risk criteria) and where cardiac etiology is suspected based on an initial evaluation, including history, physical examination, or ECG and patient is unable to exercise;6,8,10,15,16 **OR  
  
**

      * Evidence or high suspicion of ventricular arrhythmias:6,7,8,10 **OR  
  
**

      * Worsening or continuing symptoms in a patient who had a normal or submaximal exercise stress test and there is suspicion of a false negative result;20,22 **OR  
  
**

      * **** Patients with recent equivocal or borderline testing where ischemia remains a concern;8,15,20 **OR  
  
**

      * Patients on beta blocker, calcium channel blocker, and/or antiarrhythmic medication when the documentation supports that an adequate workload may not be attainable to enable a fully diagnostic exercise study;2,5 **OR  
  
**

      * History of false positive exercise stress test (e.g., one that is abnormal, but the abnormality does not appear to be due to macrovascular CAD);8,22 **OR  
  
**

      * Evaluation of chest pain syndrome after revascularization or in patients with intermediate to high pre-test probability for CAD regardless of ECG interpretability or ability to exercise;7,8 **OR  
  
**

      * High pre-test probability for CAD regardless of ECG interpretability or the ability to exercise, and a decision to perform cardiac catheterization or other angiography has not already been made;7,8,10,15 **OR  
  
**

      * Patients with HCM;14 **OR  
  
**

  2. New-onset atrial fibrillation (with no prior cardiac evaluation).10,12,13  
  

  3. Patients with disease conditions associated with CAD (e.g., atherosclerotic abdominal aortic aneurysm, peripheral vascular disease, carotid artery disease, chronic renal failure) with no stress imaging evaluation performed within the preceding 2 years and are unable to exercise.5,7,10,17  
  

  4. Patients without clear cardiac symptoms in the presence of an elevated cardiac troponin.6,8  
  

  5. Patients without cardiac symptoms who underwent a PCI (with stent) procedure more than 2 years prior or a CABG more than 5 years prior and have not undergone an evaluation for CAD within the past 2 years (stress echocardiogram, SPECT MPI, PET MPI, CMR, coronary computed tomography angiography [CCTA], cardiac catheterization) and are unable to exercise.6,7,8,15,17,18  
  

  6. Patients with established CAD who experienced an ACS event (STEMI, NSTEMI, or unstable angina) within the past 90 days provided that they did not undergo coronary angiography at the time of the acute event and are currently clinically stable.6,8  
  

  7. Evaluating new, recurrent, or worsening left ventricular dysfunction/congestive heart failure.6-8,10,23  
  

  8. Assessing myocardial viability in patients with significant ischemic ventricular dysfunction (suspected hibernating myocardium) and persistent symptoms or heart failure such that revascularization would be considered.6-9,15,23  
  

  9. Pre-operative cardiac evaluation in patients not able to exercise and who will be undergoing noncardiac surgery with one of the following6-8,15,17,19:

    * Intermediate risk for surgery (cardiac risk 1-5%), poor (<4 metabolic equivalents [METs]) or unknown functional capacity, inability to exercise adequately or ECG uninterpretable for ischemia, and the results will affect patient management decisions.
    * High risk for surgery (> 5% cardiac risk), poor (<4 METs) or unknown functional capacity, inability to exercise adequately or ECG uninterpretable for ischemia, and the results will affect patient management decisions.

  10. Asymptomatic patients with a coronary calcium Agatston score >400.6-8,17  
  

  11. Planned cardiac or other solid-organ transplant when no cardiac evaluation has been performed within the past year.10,24  
  

  12. Patients who will be treated with interleukin 2 products for various malignant disorders.25 The Food and Drug Administration (FDA) has issued a black box warning for interleukin 2 products. See the FDA drug label for the FDA black box warning: <https://labels.fda.gov/>[  
  
](https://labels.fda.gov/)

  13. Stress echocardiography for the evaluation of moderate to severe valvular heart disease, suspected pulmonary artery hypertension, and re-evaluation of exercise-induced pulmonary hypertension to evaluate response to therapy.6,26  
  

  14. Stress echocardiography for the detection and quantification of dynamic left ventricular outflow tract (LVOT) obstruction in the absence of resting LVOT in patients with HCM.14  
  

  15. CMR in patients with HCM when echocardiography is inconclusive or there are poor echocardiograph imaging windows.4  
  

  16. Evaluation of transplant coronary artery disease (TCAD) or cardiac allograft vasculopathy (CAV) in patients with a history of organ transplantation.27-40  
  

  17. Utilization of PET MPI in the determination of cardiac involvement using fluorodeoxyglucose (F-18 FDG) to diagnose cardiac sarcoidosis in patients who are unable to undergo MRI,have inconclusive MRI findings, or when high probability of disease exists even after a negative MRI. Examples of patients who are unable to undergo MRI include, but are not limited to, patients with metal implants.15,41-48  
  

  18. Utilization of PET MPI using fluorodeoxyglucose (F-18 FDG) to determine response to immunosuppressive therapy in patients diagnosed with cardiac sarcoidosis.15,41-45,47,48  
  

  19. Additional indications for PET Scans and SPECT are outlined in the CMS IOM Publication 100-03, _Medicare National Coverage Determinations (NCD) Manual_ , Chapter 1, Part 4, Sections 220.6 Positron Emission Tomography (PET) Scans, 220.6.1 PET for Perfusion of the Heart, 220.6.8 FDG PET for Myocardial Viability, and 220.12 Single Photon Emission Computed Tomography (SPECT).  
  

  20. Cardiovascular stress testing may be performed in conjunction with additional cardiac diagnostic tests including echocardiography and nuclear cardiac imaging. However, selection of the test should be made within the context of other testing modalities so that the expected information does not become redundant.  
  

  21. Patients with recently demonstrated coronary stenosis of uncertain functional significance in a major coronary branch on an anatomic imaging study (coronary angiogram or CCTA) may have one stress test with imaging.6-8,49

**  
Limitations**  
  

**The following are considered not medically reasonable and necessary:**  
  

  1. Screening for coronary artery disease in asymptomatic patients unless under specific conditions as outlined in this LCD. Please refer to CMS IOM Publication 100-02, _Medicare Benefit Policy Manual_ , Chapter 16, Section 20 Services Not Reasonable and Necessary.  
  

  2. Routine screening for CAD in asymptomatic patients with diabetes mellitus.11  
  

  3. Routine stress testing in asymptomatic patients with abnormal prior stress imaging.6,8,10  
  

  4. Routine stress testing in asymptomatic patients with obstructive or nonobstructive CAD without a revascularization procedure.6,8,10  
  

  5. Exercise testing or radiologic imaging within the first 2 years following PCI without specific symptoms (e.g., chest pain, ECG changes, etc.).8,17,18  
  

  6. Utilization of SPECT MPI, PET MPI, stress echocardiography, and CMR in patients with low pretest probability of CAD, interpretable ECG, and the ability to exercise.6-9,49  
  

  7. The routine and repetitive monitoring of patients beyond the first cardiac stress test, in the absence of a documented change in condition (e.g., new symptoms or progression of existing symptoms).  
  

  8. Cardiovascular stress testing with or without cardiac imaging if the results will not affect patient management decisions.49  
  

  9. Cardiovascular stress testing with or without cardiac imaging when a decision to perform cardiac catheterization or other angiography has already been made.49  
  

  10. Stress testing with or without imaging for pre-operative evaluation for low risk noncardiac surgery.6-8,19,49  
  

  11. Stress testing with or without imaging for pre-operative evaluation of asymptomatic patients undergoing intermediate or high risk noncardiac surgery would not be expected for patients 12 months following a normal stress echocardiography, SPECT MPI, PET MPI, CMR, coronary computed tomography angiography (CCTA), or cardiac catheterization.7,10,19  
  

  12. Utilization of SPECT MPI, PET MPI, stress echocardiography or CMR for the pre-operative evaluation of planned intermediate or high risk, noncardiac surgery, in the patient with normal or minor changes in resting ECG would not be expected for patients with no contraindications to exercise.6-8,17,19  
  

  13. Absolute contraindications to exercise stress testing (not an all-inclusive list)2,5:

    * Within 2 to 4 days of an acute myocardial infarction
    * High-risk unstable angina
    * Uncontrolled cardiac arrhythmias causing symptoms or hemodynamic compromise
    * Symptomatic severe aortic stenosis
    * Decompensated or uncontrolled congestive heart failure
    * Systolic blood pressure (BP) at rest >200 mmHG or diastolic BP at rest >110 mmHg
    * Acute pulmonary embolus or pulmonary infarction
    * Acute myocarditis or pericarditis
    * Acute aortic dissection
    * Severe pulmonary hypertension
    * Acute symptomatic medical illness

  14. Please refer to CMS IOM Publication 100-03, _Medicare National Coverage Determinations (NCDs)_ , Chapter 1, Part 4, Sections 220.6.8 FDG PET for Myocardial Viability and 220.6.1 PET for Perfusion of the Heart for additional limitations.

**  
Provider Qualifications  
  
** Exercise testing must be supervised consistent with the CMS IOM Publication
100-02, _Medicare Benefit Policy Manual_ , Chapter 15, Section 80. The
appropriately trained provider in exercise testing must be capable of
recognizing signs and symptoms of cardiac disease and capable of interpreting
the exercise test findings. Exercise testing in selected patients may be
conducted by a healthcare professional that has training in a related health
area, has appropriate training in the supervision of exercise stress tests,
and is capable of performing cardio-pulmonary resuscitation.3,50  
  

**Notice:** Services performed for any given diagnosis must meet all of the
indications and limitations stated in this LCD, the general requirements for
medical necessity as stated in CMS payment policy manuals, any and all
existing CMS national coverage determinations, and all Medicare payment rules.

Multiple guidelines and appropriate use criteria are available for
cardiovascular stress testing with and without cardiac imaging.  
  
Pretest probability is used to determine if cardiovascular stress testing is
appropriate and whether cardiac imaging is also appropriate.5-10,15 The
pretest probability of CAD is based on age, gender, and symptoms.5  
  
 **Evidence-based guidelines  
  
Exercise stress testing without cardiac imaging  
  
**Wolk et al10 provided the 2013 multimodality appropriate use criteria for
the detection and risk assessment of stable ischemic heart disease. An
exercise stress test is recommended for patients exhibiting cardiac symptoms,
including otherwise unexplained angina equivalent symptoms with normal or
minor changes in resting ECG and no contraindications to exercise.5-10
Exercise stress testing is also recommended for patients without cardiac
symptoms who underwent a percutaneous coronary intervention (PCI) (with a
stent) procedure or a coronary artery bypass graft (CABG) more than 2 years
prior and have not undergone an evaluation for CAD within the past 2 years
[stress echocardiogram, SPECT MPI, PET MPI, CMR, coronary computed tomography
angiography (CCTA), cardiac catheterization] and are able to
exercise.6-8,10,15,17,18 Evidence-based guidelines also recommend an exercise
stress test for patients with established CAD who experienced an acute
coronary syndrome (ACS) event (ST segment elevation myocardial infarction
[STEMI], a Non-ST segment elevation myocardial infarction [NSTEMI], or
unstable angina) within the past 90 days provided that they did not undergo
coronary angiography at the time of the acute event and are currently
clinically stable and able to exercise.6,8,10  
  
 **Evidence-based guidelines  
  
**  
 **Exercise stress testing without cardiac imaging for patients who can
exercise and stress testing with cardiac imaging for patients who are unable
to exercise  
  
** Multiple articles address that the confounders of stress ECG interpretation
include resting ST-segment depression, left ventricular hypertrophy with
repolarization abnormalities, left bundle branch block, various medications,
pre-excitation pattern such as Wolff-Parkinson-White, and ventricular paced
rhythm.2,5,8,9,15,21 An exercise or pharmacological imaging study should be
considered for patients with an abnormal resting ECG due to left bundle branch
block, pre-excitation syndrome, left ventricular hypertrophy (LVH), new-onset
atrial fibrillation, or digoxin therapy, because the accuracy of the exercise
ECG in detecting provocable ischemia is reduced.2,5,10,12,13 An exercise or
pharmacological imaging study should also be considered for patients with
disease conditions associated with CAD (e.g., atherosclerotic abdominal aortic
aneurysm, peripheral vascular disease, carotid artery disease, chronic renal
failure) with no evaluation performed within the preceding 2 years.5,7,10,17  
  
Shen et al16 provided the 2017 American College of Cardiology/American Heart
Association guideline for the evaluation and management of patients with
syncope. Stress testing is recommended for patients with an intermediate or
high CHD risk (ATP III risk criteria) who have experienced syncope (an abrupt,
transient, complete loss of consciousness) when cardiac etiology is suspected
based on an initial evaluation, including history, physical examination, or
ECG. An exercise stress test is recommended for patients who can exercise and
pharmacological stress imaging is recommended for patients who are unable to
exercise.6,8,10,15,16  
  
The guideline on perioperative cardiovascular evaluation and management of
patients undergoing noncardiac surgery states perioperative cardiac and long-
term risks are increased in patients who are unable to perform 4 METs of work
during daily activities.19 Perioperative myocardial ischemia and
cardiovascular events were more common in those with poor functional status.
Patients undergoing low-risk noncardiac surgery and patients undergoing
elevated risk noncardiac surgery with moderate or greater functional capacity
do not require cardiovascular stress testing. For patients undergoing elevated
risk noncardiac surgery with poor (<4 METs) or unknown functional capacity and
further testing will impact decision making or perioperative care, it may be
reasonable to perform cardiovascular stress testing.  
  
Fleisher et al19 recommends pre-operative cardiac evaluation in patients
undergoing noncardiac surgery with an intermediate risk for surgery (cardiac
risk 1-5%) or with a high risk for surgery (> 5% cardiac risk) and the results
will affect patient management decisions. In this regard, exercise stress
testing is recommended for patients who are able to exercise and pharmacologic
stress testing for patients who are unable to exercise.  
  
 **Stress testing with cardiac imaging  
  
** Pharmacological imaging studies may be appropriate for those patients who
are unable to reach 75-100 percent of their age-predicted maximum heart rate
by physiologic exercise.  
  
The SPECT MPI is highly accurate to diagnose flow-limiting CAD and to stratify
risk of ischemic heart disease events.9 A strength of SPECT is the
availability of robust software programs for the interpretation of MPI. Hendel
et al17 provided a multicenter assessment of the use of single-photon emission
computed tomography myocardial perfusion imaging with appropriateness
criteria. Dorbala et al24 has also provided SPECT MPI guidelines. Consistent
with these guidelines, stress testing with cardiac imaging is recommended for
patients without cardiac symptoms who underwent a PCI (with stent) procedure
or a CABG more than 2 years prior and have not undergone an evaluation for CAD
within the past 2 years [stress echocardiogram, SPECT MPI, PET MPI, CMR,
coronary computed tomography angiography (CCTA), cardiac catheterization] and
are unable to exercise.6-8,15,17,18 A stress test with cardiac imaging is also
recommended for patients with cardiac symptoms who had a PCI procedure (with
stent) or a CABG procedure more than 5 years ago and who have not undergone an
evaluation for CAD within the past 2 years [stress echocardiogram, SPECT MPI,
PET MPI, CMR, CCTA, cardiac catheterization].6-8,15,17  
  
Evidence-based guidelines also recommend stress testing with cardiac imaging
for patients experiencing new, recurrent, or worsening cardiac symptoms,
including otherwise unexplained angina equivalent symptoms, and any of the
following: a) Physical inability to perform a maximum exercise
workload,2,5,6,8-10,15,20 b) New or previously unrecognized uninterpretable
ECG,2,5,6,8-10 c) ECG is uninterpretable for ischemia due to any one of the
following2,5,8,9,15,21: 1) Complete left bundle branch block (right bundle
branch does not render ECG uninterpretable for ischemia); 2) Ventricular paced
rhythm; 3) Pre-excitation pattern such as Wolff-Parkinson-White; 4) A > 1 mm
ST segment depression (Not nonspecific ST/T wave changes); 5) Left ventricular
hypertrophy (LVH) with repolarization abnormalities, also called LVH with
strain (Not without repolarization abnormalities or by voltage criteria); or
6) Patient on digoxin therapy. Stress testing with cardiac imaging is also
recommended for patients with a history of CAD based on a prior anatomic
evaluation of the coronary arteries or a history of CABG or PCI.6,8,15  
  
Consistent with evidence-based guidelines, stress testing with cardiac imaging
is recommended for patients with the following conditions: a) Evidence or high
suspicion of ventricular arrhythmias,6-8,10 b) Worsening or continuing
symptoms in a patient who had a normal or submaximal exercise stress test and
there is suspicion of a false negative result,20,22 c) Patients on beta
blocker, calcium channel blocker, and/or antiarrhythmic medication when the
documentation supports that an adequate workload may not be attainable to
enable a fully diagnostic exercise study,2,5 d) History of false positive
exercise stress test (e.g., one that is abnormal, but the abnormality does not
appear to be due to macrovascular CAD),22 e) Evaluation of chest pain syndrome
after revascularization or in patients with intermediate to high pre-test
probability for CAD regardless of ECG interpretability or ability to
exercise,7,8 and f) High pre-test probability for CAD regardless of ECG
interpretability or the ability to exercise, and a decision to perform cardiac
catheterization or other angiography has not already been made.7,8,10,15  
  
 **Meta-Analysis  
  
** **Stress testing with cardiac imaging  
  
**  
The Lipinski et al article was a meta-analysis which showed that stress CMR
provided excellent prognostic stratification of patients with known or
suspected CAD.1 Patients with a negative stress CMR had a <1% annualized event
rate for cardiovascular death or nonfatal myocardial infarction. Patients with
a positive stress CMR had a 5% annualized event rate. The presence of late
gadolinium enhancement (LGE) during CMR suggested an increased risk for major
adverse cardiovascular events. This imaging modality not only provides
assessment of ischemia and recognition of LGE but can also identify valvular
heart disease and assess cardiac structure and function. Stress CMR is
considered to be comparable to other stress testing modalities in patients who
cannot exercise. The Leiner et al position paper supports that in addition to
assessing for myocardial ischemia, CMR can also distinguish scar from
hibernating myocardium, provide information about valvular function, the
presence of myocardial fibrosis, the presence of morphological abnormalities,
and provide an assessment of dynamic obstruction. This is especially valuable
in patients in whom good quality echocardiography images could not be obtained
due to technically difficult acoustic windows.3,4 The 2020 AHA/ACC Guideline
for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy
indicates that while echocardiography continues to be the foundational imaging
modality for patients with HCM, CMR will also be helpful in many patients,
especially those in whom there is diagnostic uncertainty, poor
echocardiographic imaging windows, or where uncertainty persists regarding
decisions around implantable cardioverter-defibrillator (ICD) placement.4  
  
The appropriate use criteria for echocardiography is a meta-analysis that
addresses appropriate use of echocardiography.6 Stress echocardiography is
recommended for asymptomatic patients with a coronary calcium Agatston score
>400, for patients with new or worsening symptoms with a previous abnormal
stress test and the inability to exercise. A stress echocardiography is also
recommended for evaluating inducible ischemia in patients with an intermediate
risk for coronary artery blockages and have established CAD, experienced an
ACS event (STEMI, NSTEMI, or unstable angina) within the past 90 days provided
that they did not undergo coronary angiography at the time of the acute event
and are currently clinically stable. Additionally, stress echocardiography is
recommended to assess chronic valvular disease, pulmonary hypertension, new,
recurrent, or worsening left ventricular dysfunction/congestive heart failure,
to assess patients without clear cardiac symptoms in the presence of an
elevated cardiac troponin, and to evaluate patients with recent equivocal or
borderline testing where ischemia remains a concern. Stress echocardiography,
as well as myocardial perfusion imaging or cardiac magnetic resonance is also
recommended to assess myocardial viability in patients with significant
ischemic ventricular dysfunction (suspected hibernating myocardium) and
persistent symptoms or heart failure such that revascularization would be
considered.49 In addition, the guideline for the diagnosis and treatment of
hypertrophic cardiomyopathy (HCM) addresses the use of stress echocardiography
for the detection of dynamic LVOT obstruction.14  
  
Cardiac involvement in sarcoidosis may lead to adverse outcomes such as
advanced heart block, arrhythmias, cardiomyopathy, or death. Multiple articles
support F-18 FDG PET MPI is indicated to diagnose cardiac sarcoidosis in
patients who are unable to undergo MRI, have inconclusive MRI findings, or
when high probability of disease exists even after a negative MRI. The PET MPI
is also indicated to determine response to immunosuppressive therapy in
patients diagnosed with cardiac sarcoidosis.15,41-48 The PET MPI can be safely
performed on patients with intracardiac devices and advanced renal disease and
is considered to be an appropriate tool to predict and assess response under
therapy.41,44,46,47,51-53  
  
Multiple articles address the increased risk for premature cardiovascular
disease following organ transplantation.10,27-35 There are unique factors in
organ transplant recipients that include underlying comorbidities and
metabolic effects of immunosuppression.27 In this regard, the Ducloux et al
study demonstrates the cumulative impacts of traditional and nontraditional
cardiovascular risk factors in renal transplant recipients.28 Also, according
to Gamba et al, cyclosporine, regardless of the blood cyclosporine levels, is
the main risk factor for coronary artery disease.29 Additionally, Tepperman
et.al noted that although immunosuppressive agents are sufficient to minimize
allograft rejection and promote short-term survival after transplantation, a
major limitation to longer-term survival is the development of allograft
vasculopathy.30 Central to development of allograft vasculopathy is
endothelial damage and subsequent dysfunction. The factors contributing to
endothelial dysfunction include organ preservation solutions, ischemia and
reperfusion injury, acute allograft rejection episodes, dyslipidemia,
hypertension, diabetes mellitus, and the use of immunosuppressive drugs.
Notably, many of the currently used immunosuppressants cause endothelial
dysfunction after transplantation.  
  
The Kazmirczak et al article found that regadenoson stress CMR imaging is safe
and well tolerated in heart transplant recipients.36 An abnormal regadenoson
stress CMR identifies heart transplant recipients at a higher risk for major
adverse cardiovascular events. Also, Kan and Bangalore found that among renal
transplant recipients, SPECT-MPI predicted risk of cardiovascular death and
cardiovascular hospitalization events.38 The Sade et al article also concluded
that echocardiographic coronary flow reserve is very sensitive for detecting
cardiac allograft vasculopathy and increases the diagnostic accuracy of
dobutamine stress echocardiography in heart transplant recipients.39
Additionally, Elhendy et.al found dobutamine stress myocardial perfusion
imaging is a safe and feasible method for evaluation of coronary artery
disease in heart transplant recipients.40 Evidence-based guidelines10 also
recommend stress imaging prior to planned cardiac or other solid-organ
transplant.  
  
 **Situations in which cardiovascular stress testing is not recommended  
  
** Stress testing with or without imaging for pre-operative evaluation of
asymptomatic patients undergoing intermediate or high risk noncardiac surgery
would not be expected for patients 12 months following a normal stress
echocardiography, SPECT MPI, PET MPI, CMR, coronary computed tomography
angiography (CCTA), or cardiac catheterization.7,10,19 Also, utilization of
SPECT MPI, PET MPI, stress echocardiography or CMR for the pre-operative
evaluation of planned intermediate or high risk, noncardiac surgery, in the
patient with normal or minor changes in resting ECG would not be expected for
patients with no contraindications to exercise6-8,17,19  
  
The review of the American Diabetes Association standards of medical care in
diabetes 2018 states routine screening for CAD in asymptomatic patients is not
recommended as it does not improve outcomes if atherosclerotic cardiovascular
disease risk factors are treated. Screening is not recommended in part because
high risk patients should already be receiving intensive medical therapy-an
approach that provides benefit similar to that of invasive
revascularization.11 The review states to consider investigations for CAD in
the presence of atypical symptoms, signs and symptoms of associated vascular
disease, or electrocardiogram abnormalities.  
  
Absolute and relative contraindications to exercise testing are addressed by
Henzlova and Gibbons.2,5 Although exercise testing is generally a safe
procedure, both myocardial infarction and death have been reported at a rate
of approximately 1 per 2500 tests. Therefore, it is vital to use good clinical
judgement in decisions regarding which patients should undergo exercise
testing.  
  
Qaseem et al49 discussed the clinical practice guideline for diagnosis of
stable ischemic heart disease and indicated pharmacologic stress imaging by
MPI, echocardiography, or CMR are not recommended for patients with an
interpretable ECG and who are able to exercise. Cardiovascular stress testing
with or without cardiac imaging is also not recommended when a decision to
perform cardiac catheterization or other angiography has already been made or
for pre-operative evaluation for low risk noncardiac surgery. Also, only one
type of stress test should be performed in patients who recently demonstrated
coronary stenosis of uncertain functional significance in a major coronary
branch on an anatomic imaging study (coronary angiogram or CCTA).
Additionally, consistent with evidence-based guidelines, exercise testing or
radiologic imaging performed within 2 years of PCI without specific symptoms
(e.g., chest pain, ECG changes, etc.) is not recommended.8,17,18

Cardiac stress tests play an important role in the diagnosis and management of
cardiovascular disease. Pretest probability is used to establish if
cardiovascular stress testing or cardiac imaging is appropriate. Multiple
guidelines and appropriate use criteria are available for cardiovascular
stress testing with and without cardiac imaging. Meta-analyses of literature
offer recommendations regarding the suitable use of exercise stress testing
and pharmacologic stress testing in the diagnosis and treatment of symptomatic
or asymptomatic patients with known or suspected CAD. Pharmacologic imaging
studies may be appropriate for those patients who are unable to reach 75-100
percent of their age-predicted maximum heart rate by physiologic exercise. The
various guidelines and literature also address absolute and relative
contraindications to exercise testing.

Studies have shown that perioperative myocardial ischemia and cardiovascular
events were more common in those with poor functional status. Therefore, it
may be reasonable to perform cardiovascular stress testing in patients
undergoing high risk noncardiac surgery with poor (<4 METs) or unknown
functional capacity as this information could possibly impact decision making
or perioperative care. However, consistent with evidence-based guidelines,
patients who will be undergoing low-risk noncardiac surgery and patients who
will be undergoing elevated risk noncardiac surgery with moderate or greater
functional capacity do not require cardiovascular stress testing.

The SPECT MPI is highly accurate to diagnose flow-limiting CAD and to stratify
risk of ischemic heart disease events. A strength of SPECT is the availability
of robust software programs for the interpretation of MPI. Studies have also
shown that the SPECT-MPI has successfully predicted risk of cardiovascular
death and cardiovascular hospitalization events in renal transplant
recipients. Additionally, studies have indicated that dobutamine stress MPI is
a safe and feasible method for evaluation of coronary artery disease in heart
transplant recipients.

Studies show that patients with a negative stress CMR had a <1% annualized
event rate for cardiovascular death or nonfatal myocardial infarction whereas
patients with a positive stress CMR had a 5% annualized event rate suggesting
that the stress CMR provides an excellent prognostic stratification of
patients with known or suspected CAD. The stress CMR not only provides
assessment of ischemia and identifies the presence of LGE but can also
recognize valvular heart disease and assess cardiac structure and function.
Stress CMR also seems to be comparable to other stress testing modalities.
Studies have shown that an abnormal regadenoson stress CMR identifies heart
transplant recipients at a higher risk for major adverse cardiovascular
events. Studies indicate CMR imaging is safe and well tolerated as a
prognostic stratification tool for recognizing valvular heart disease,
assessing cardiac structure and function and identifying heart transplant
recipients at a higher risk for adverse cardiovascular events.

Stress echocardiography is used for patients with known or suspected CAD who
are symptomatic or asymptomatic. Stress echocardiography is used to assess
chronic valvular disease and pulmonary hypertension and for the detection of
LVOT obstruction. Also, studies have found that the echocardiographic coronary
flow reserve is very sensitive for detecting cardiac allograft vasculopathy
and increases the diagnostic accuracy of dobutamine stress echocardiography in
heart transplant recipients.

The F-18 FDG PET MPI is indicated to diagnose cardiac sarcoidosis in patients
who are unable to undergo MRI, have inconclusive MRI findings, or when high
probability of disease exists even after a negative MRI. The PET MPI is also
indicated to determine response to immunosuppressive therapy in patients
diagnosed with cardiac sarcoidosis. The PET MPI can be safely performed on
patients with intracardiac devices and advanced renal disease and is
considered to be an appropriate tool to predict and assess response under
therapy.

Stress echocardiography, SPECT MPI, PET MPI and CMR are considered equivalent
diagnostic tests. However, in addition to myocardial ischemia, stress
echocardiography can provide information that is not obtainable with MPI, such
as valve function, assessment of pulmonary pressure, and assessment of dynamic
obstruction.