Advanced Imaging Section

Section Lead:

• Neha Mantri, MD (@NehaMantri_MD)

Section Contributors:

• Talal Alnabelsi, MD
• Jorge Penalver, MD
• Sagar Ranka, MD (@RankaSagar)
• Siva Taduru, MD
• Srilakshmi Vallabhaneni, MD

• General Principles: 
• Myocardial injury is common among COVID-19 patients (up to 30%) and is associated with higher in-hospital mortality. 
• Avoid unnecessary cardiac imaging to reduce viral spread, protect healthcare professionals and limit PPE usage. 
• In patients with a low pre-test probability and/or alternative explanation for troponin elevation is found then cardiac imaging can be deferred. 
• Invasive angiography is recommended if the patient is high risk or suspicion for ACS is high (STEMI or high-risk NSTEMI).
• Intermediate risk for CAD / ACS then TTE/POCUS or CCTA is reasonable (Cosyns et al, Eur Heart J, 2020).
• TTE and further imaging should only be performed when findings will change management (Skulstad et al, EHJ, 2020)

• TTE Indications:
• Cardiac murmurs of unknown etiology, profoundly elevated cardiac biomarkers, or acute coronary syndrome (Shi et al, JAMA Cardiol, 2020; Zhou et al, Lancet, 2020)
• Acute dyspnea or pulmonary edema on chest imaging
• Suspected myocarditis or signs and symptoms of new onset acute heart failure 
• Cardiogenic shock or hemodynamic instability, including acute pulmonary embolism (Chen et al, Lancet, 2020)
• Persistent malignant arrhythmias (Guo et al, JAMA Cardiol, 2020)
• ST segment elevation on electrocardiography, concern for "STEMI mimicker" (Banglaore et al, NEJM, 2020).  
• Severe hemodynamic instability requiring mechanical circulatory support (i.e. extracorporeal membrane oxygenator), monitor for left ventricular function recovery (Tavazzi et al, EHJ, 2020)  

Algorithm from ASE for Determining Indication and Level of Protection of Patients and Echocardiography Service Providers during COVID-19

• Safe re-introduction of cardiovascular services:
• Guidance from North American Society Leadership (Wood et al, Can J Cardiol, 2020)
• Continued collaboration between public health officials, health authorities and cardiovascular care providers
• Important considerations when implementing guidance:
• Collaborative plan for PPE provision and COVID-19 screening must be in place
• If both tests have similar efficacy; consider the less invasive or alternate imaging modality
• Maintain reserve capacity to deal with a second surge
• Protection of patients and healthcare workers:
• Maintain physical distancing
• Consolidate tests into one visit
• Utilize virtual pre-procedure clinics and virtual consents
• Consider pre-test/procedure COVID-19 screening
• Response levels will vary by region and by testing modalities and the transition between levels requires close collaboration with healthcare authorities

• TTE Findings:
• Retrospective study of 112 patients with suspected myocardial injury in patients with COVID-19 (Deng et. al. Int J Cardiol. 2020)
• Non-severe (45, 40%) and severe (67, 59.8%)-no significant differences of cardiac chamber sizes between patients in non-severe and severe groups. (see Table below) There were 6 (5.4%) patients with LVEF <50% and no patients had LVEF <40%.
• The maximum depth of pericardial effusion was 6.2 ± 1.1mm and there were more patients in the severe group with this small amount of pericardial effusion (19 [28.3%] vs 3 [6.7%], p < 0.01).
• 15 (13.4%) patients presented with signs of pulmonary hypertension

Table: Imaging findings of patients with confirmed COVID-19. (Deng et. al. Int J Cardiol. 2020)

Table: Echocardiographic manifestations and possible causes in critically ill COVID-19 patients. (Peng, et al. Crit Care. April 2020) 

• Role & Protocol for Point of Care Ultrasound (POCUS) (Johri et al, ASE, 2020): 

1. POCUS should often be considered first line to aid in patient triaging given rapid assessment of bi-ventricular function
2. ASE recommends the following selected views: parasternal long axis, parasternal short axis, apical, and subcostal IVC views. ASE proposed protocol
3. POCUS indications:
4. Detection and characterization of pre-existing CV disease
5. Early identification of worsening cardiac dysfunction
6. Elucidation of specific COVID-19 CV abnormalities including pericardial effusion, myocarditis, cardiogenic shock
7. Deep vein thrombosis, pulmonary embolism, RV dysfunction, acute pulmonary hypertension
8. LV systolic dysfunction, either global or regional, associated with myocarditis, stress-induced cardiomyopathy pattern, epicardial or microvascular coronary thrombosis 
9. Lung POCUS can be performed when radiographic studies such as CT are limited 
10. EKG monitoring may be omitted and measurements can be performed offline. The reports should reflect the limited nature of the performed study.

ASE Protocol for POCUS Evaluation in COVID-19 Suspected or Confirmed Patients:

• Case Reports of TTE Findings: spectrum of findings based on case reports. Two main patterns seen include: 1) global biventricular myocardial dysfunction (suggesting ACS or myocarditis), 2) right ventricular strain pattern (suggesting pulmonary embolism)
• Left ventricular systolic function (Inciardi et al, JAMA Cardiol, 2020) and dilatation (Kim et al, EHJ, 2020).
• Left ventricular dysfunction with regional or global variation in myocarditis or myo-pericarditis (Inciardi, et al. JAMA Cardiology, 2020) 
• Left ventricular apical ballooning with hyperkinetic basal segment suggestive of typical takotsubo (Meyer et al, EJH, 2020)
• Segment wall motion abnormalities with inferolateral hypokinesis, consistent with reverse-takotsubo (Sala et al, EHJ, 2020)  
• Regurgitant valvular lesions, including mitral or tricuspid regurgitation in patients with underlying cardiomyopathy, incidence remains unknown
• Pericardial effusion (Inciardi et al, JAMA Cardiol, 2020) with cardiac tamponade (Hua et al, EHJ, 2020), (Dabbagh et al, JACC Case Rep, 2020) 
• Right ventricular failure due to PE (Ullah et al, JACC Case Rep. April 2020): 59-year-old women presented with weakness and mechanical fall along with mild productive cough with yellowish sputum. She tested positive for PCR SARS-CoV-2 and persistently hypoxic. CTA showed large bilateral central and proximal segmental pulmonary artery emboli and linear saddle PE (Figure 1). Echo showed RV dilatation with reduced function along with severe tricuspid regurgitation (Figure 2)

Figure 1: CT of the Chest and CT Pulmonary Angiography: (A) Axial unenhanced chest computed tomography (CT) scan obtained on day 1 after the onset of symptoms shows bilateral areas of ground-glass interstitial opacities. (B) Computed tomography pulmonary angiography demonstrates multiple bilateral filling defects involving lobar and segmental branches of the pulmonary artery (yellow arrow) and a linear saddle pulmonary embolus (red arrow).

Figure 2: Bedside TTE (A) Parasternal short-axis view of the heart showing a dilated right ventricle (red arrow). (B) Doppler echocardiographic view of severe tricuspid regurgitation.

• Acute DVT and PE due to hypercoagulable state (Hu et al, EHJ, 2020). Severely reduced right ventricular function and dilatation can can be associated with acute pulmonary embolism (Xie et al,RSNA, 2020) and severe pulmonary hypertension (Danzi et al, EHJ, 2020)

* Of note: TTE may be normal in patients with despite significant EKG abnormalities

1. Special considerations: 
2. Stress testing (including dobutamine or exercise stress echocardiography): not indicated in active COVID19 due risk of coughing and deep breathing 
3. Echo contrast: can be useful for myocardial in intubated patients with poor echocardiographic windows, however ensure to have on cart upon entry into patient room 
4. Left ventricular angiography: suggested as an alternative to TTE in hemodynamically stable STEMI patients (Skulstad et al, EHJ, 2020) 
5. Additional Resources:
6. Best practices for sonographers available on ASE website (Mitchell et al, ASE website) 
7. Recommendations on cleaning, disinfecting and protection of equipment and laboratory facilities detailed on ASE and ESC websites (Skulstad et al, EHJ, 2020; Kirkpatrick et al, ASE, 2020)

Precaution and Types of PPE outlined by ASE

1. Transesophageal Echocardiogram (TEE) 
2. Modified Appropriate Use Criteria in setting of COVID-19: 
3. Defer all elective TEEs: only perform those studies which change immediate management. Suspend elective non-essential cases (Skulstad EHJ, 2020; Kirkpatrick, ASE)
4. Peri-operative TEE will likely be performed in OR, structural heart and catheterization rooms, or the ICU. Patients with suspected or confirmed COVID-19 should undergo procedures in dedicated COVID-19 rooms or may be admitted to ICU rooms. 
5. Recommend performing abbreviated exams limited to patient’s clinical condition 
6. Consider alternative imaging modalities including CT/CMR/repeat TTE, if possible
7. Trainees should be knowledgeable and trained to reduce infection transmission. Do not recommend involvement of medical students or residents in performing TEEs in suspected or confirmed COVID-19 patients 
8. Peri-operative or peri-procedural TEE when benefits outweigh risks (Kirkpatrick et al, ASE website) 
9. Infective endocarditis with valvular or paravalvular involvement
10. Stanford type A dissection, particularly in presence of associated complications (aortic insufficiency, aortic root involvement, pericardial effusion) 
11. Initiation of temporary or durable MCS 
12. ACS with mechanical complications (ventricular septal defect, LV wall rupture, papillary muscle rupture) 
13. Prosthetic valve assessment
14. Cleaning, disinfecting, protection
15. Adhere by the same cleaning protocols, however, consider shutting down the TEE procedural room for 60 minutes post-exam to ensure > 99% of particles have dissipated as 6 air changes per hour for a non-negative pressure room. 
16. Recommended step-wise approach per ASE recommendations for TEE
17. Examples of use of a standard laparoscopic sleeve to reduce aerosolized contamination during the TEE exam. The TEE probe is inserted into the sleeve drape and the mouthpiece secured to the stretchable end of the drape. 

Figure: The TEE probe is inserted into the sleeve drape and the bite block/mouthpiece is secured to the stretchable end of the drape and secured with the sleeve’s tapes (Bracco, Can J Anesth, 2020)

Figure: Similar concept demonstrating: A: TEE probe with bite block pre-inserted. B: Insert TEE probe in the designated space in the middle of probe, C, D: TEE probe tip coming out of the US probe cover after making a hole (Jain, J Cardiothorac Vasc Anesth, 2020)

Stepwise Algorithm for TEE Examination in suspected or Confirmed COVID-19 patient by the ASE

1. SCCT Guidelines (Guideline Document)
2. For patients with confirmed or suspected COVID, the benefit of CCT scanning is likely lower than risk of COVID exposure. Recommend discussion on case by case basis. 
3. If CCT is deemed necessary (suspected or confirmed cases):
4. Ensure proper use of PPE
5. Appropriate environmental cleaning and decontamination
6. Defer CCT exams which can safely be postponed

1. Diagnostic utilities*:
2. Rule out LA thrombus; recommended over TEE 
3. Exclude CAD or high risk anatomy that could defer hospital admission
4. May be useful in carefully selected patients with elevated cardiac enzymes and possible ACS
5. Consider for quadruple rule out (PE, myocarditis, CAD and pneumonia)
6. Consider urgent CCT in symptomatic prosthetic valve dysfunction, endocarditis

*Use of CCT in these scenarios may reduce PPE utilization

1. Imaging findings:
2. Mid and basal LV hypokinesis with apical sparing suggestive of reverse-takatsubo (Sala et al, EHJ, 2020)
3. Absence epicardial coronary artery disease, despite ST elevation on EKG (Sala et al. EHJ, 2020)
4. Hypertrophied myocardium (edema) with sub-endocardial perfusion defect (Kim et al, EHJ, 2020)
5. Focal sub-epicardial perfusion defect (delayed imaging, after 7 min)*

*Protocol: obtain CCTA, re-inject contrast and obtain delayed post contrast image after 7min

1. SCMR guidelines (Guideline document)
2. All CMR requests should be reviewed by an imaging physician. Defer routine scans
3. CMR in COVID-19 patients not to be performed unless absolutely necessary and should be discussed on a case-by-case basis with the cardiology consult team
4. Urgent CMR’s should be short, targeted and focused on answering a specific question
5. If possible establish a dedicated CMR for COVID-19 patients (cardiac and general cases)
6. Allow 70 min for decontamination post scan
7. In COVID-19 patients, 1 tech wearing full PPE is responsible for helping the patient in and out of the scanner room and in sanitizing the room/equipment. 
8. No difference in scan interpretation or post processing for COVID-19 patients
9. Pay attention to non-cardiac findings especially pulmonary infiltrates and suggest further evaluation with CT Chest if pulmonary abnormalities present
10. Imaging findings
11. Wall thickness: 
12. Increased - suggestive of edema (Inciardi et al, JAMA Cardiol, 2020; Sala et al, EHJ, 2020; Kim et al, EHJ, 2020) (Figures 1, 2) 
13. LV function:
14. Global LV hypokinesis (Inciardi et al, JAMA Cardiol, 2020)
15. Regional hypokinesis (reverse takatsubo) (Sala et al, EHJ, 2020)
16. Short tau inversion recovery and T2-mapping:
17. Diffuse high signal intensity - suggestive of edema (Inciardi et al, JAMA Cardiol, 2020; Kim et al, EHJ, 2020)
18. Native T1 and ECV
19. Diffusely increased (Kim et al, EHJ, 2020)
20. LGE
21. Diffuse, involving LV and RV (Inciardi et al, JAMA Cardiol, 2020)
22. Transmural affecting anterior and lateral walls (Kim et al, EHJ, 2020)
23. Mid-myocardial, resolving on follow-up CMR (Siripanthong et al, Heart Rhythm, 2020) (Figure 3)
24. Absent
25. Pericardial effusion:
26. Absent
27. Circumferential pericardial effusion (Inciardi et al, JAMA Cardiol, 2020)

Figure 1

Figure 1: LVEF-64% by CMR with diffuse edema in the mid to basal left ventricular walls on short T1 inversion recovery confirmed by T1 and T2 mapping (average native T1 = 1188 ms, normal value <1045; average T2 = 61 ms, normal value <50). No late gadolinium enhancement was noted. (Inciardi et al, JAMA Cardiol, 2020)

Figure 2

Figure 2: Cardiac CT with hypertrophied myocardium due to edema and a sub-endocardial perfusion abnormality in the lateral wall. CMR of the same patient showing a sub-endocardial perfusion defect in the lateral wall. (Kim et al, EHJ, 2020)

Figure 3

Figure 3: Mid-myocardial LGE on CMR (left panel) which resolved on follow up CMR scan, suggesting myocardial edema during the acute phase. (Siripanthong et al, Heart Rhythm, 2020)

• General Considerations
• 18F -FDG PET/CT uptake in lung and lymph nodes due to infectious and inflammatory related processes causing early physiological changes/ 
• These are not specific for COVID-19 infection and 18F-FDG PET/CT not recommended for evaluation of patients with known or suspected COVID-19 infection (due to complexity in performing 18F-FDG PET/CT imaging with increased risk of disease transmission due to longer time). 
• Chest CT remains the suggested imaging method to evaluate COVID-19 pneumonia. 
• However, nuclear medicine physicians should pay attention to incidental findings of interstitial pneumonia (with ground-glass opacities) suspected for COVID-19 infection detected at 18F-FDG PET/CT (Treglia et al. Clin Transl Imaging, 2020) 

• Case Reports Showing Use of Nuclear Imaging
• Four patients in Wuhan- suspected of COVID-19, SARS-CoV-2 nucleic acid testing was not performed in three patients, was negative times two (RT-PCR) in one patient (Chunxia Qin et al, Eur J Nuc Med Mol Imaging, 2020) 
• All patients had peripheral ground glass opacities and/or lung consolidations in more than two pulmonary lobes high 18F-FDG uptake in the lung with lymph node involvement
• Tumors presenting as ground glass opacities are not FDG-avid, but the high tracer update with COVID-19 pulmonary infections reflects a significant inflammatory burden. Increased nodal FDG uptake in 3 out of the four cases with no enlargement suggesting possible lympadenitis
• 18F-FDG PET/CT not used in the emergency setting but may play a complementary diagnostic role in COVID-19- especially in early stages when clinical symptoms are not specific

Figure: Multiple peripheral FDG-avid GGOs in the right lung and multiple FDG-positive nodes in the mediastinum and the right subclavian region (Chunxia Qin et al, Eur J Nuc Med Mol Imaging, 2020) 

• 37-YOM with vertigo, fever, and diarrhea. 18F-FDG uptake in the lungs corresponding with ground-glass opacities seen on Chest CT.

Figure: PET/CT imaging revealed 18F-FDG uptake in bilateral lung parenchyma with corresponding ground glass opacities on chest CT.(Liu et al, Clin Nuc Med, 2020)

• SPECT/CT for diagnosis of PE in COVID-19 patients (Lu et al. Eur J Nucl Med Mol Imaging, 2020) 
• Perfusion SPECT/CT to diagnose PE during COVID-19 pandemic
• In symptomatic patients with contraindications for CT pulmonary angiography (CTPA) or non-diagnostic CTPA, obtain planar perfusion images first. If normal, PE ruled out.
• When planar perfusion images showed abnormality, further Q-SPECT/CT should be obtained. The PE diagnosis on Q-SPECT/CT images can be made using “MSKCC Q-SPECT/CT criteria” 
• This practice can make SPECT/CT diagnose two very important clinical findings at one- PE and identify if there are suspicious CT findings of COVID-19 pneumonia.
• Ventilation studies carry risk of airborne radioaerosol contamination hence was abolished at their center (MD Anderson)

Figure: Diagnostic algorithm for nuclear medicine evaluation of PE during COVID-19 pandemic (Lu et al. Eur J Nucl Med Mol Imaging, 2020) 

• General principles for COVID-19 protection: 
• ASNC Guidance and Best Practices
• Reschedule non-urgent visits
• Reschedule elective surgeries and procedures
• Using separate spaces for patients with known or suspected COVID-19 to prevent spread
• Ensure supplies are available
• Promote use of telehealth
• Test as Scheduled (Priority Class 1)
• Myocardial perfusion imaging for ischemic heart disease in the following scenarios:
• Recent acute coronary syndrome: evaluation of ischemia in a moderate to high-risk patients considered for urgent coronary revascularization
• New or accelerating symptoms Canadian Cardiovascular Society Class II-IV where diagnosis of CAD is uncertain (intermediate pretest likelihood), or where suspicion of CAD, is high but coronary angiography has greater risk.
• Preoperative evaluation: evaluation of ischemia in moderate to high-risk patients for pre-operative evaluation, in whom surgical procedure is urgent and revascularization is an option.
• 18F-FDG PET viability
• Patient with ongoing symptoms being considered for CABG in the next 2 weeks where viability imaging will impact revascularization decision
• 99mTc- PYP imaging for transthyretin cardiac amyloidosis
• Heart failure where transthyretin cardiac amyloidosis is suspected (Only in select cases)
• 18F-FDG PET for sarcoidosis
• Initial evaluation: Heart block or VT and suspected cardiac sarcoidosis (perform using caution)
• 18F-FDG PET for infective endocarditis
• Initial evaluation: Suspected prosthetic or device infection
• MUGA scan for LVEF estimation
• Assessment of left ventricular function, as an alternative to echocardiography with short duration of patient-staff interaction.
• Initial evaluation: Prior to initiation of cardiotoxic chemotherapy
• Follow-up evaluation: Prior to subsequent chemotherapy
• Organ transplant
• Liver transplant: preoperative evaluation in patients with intermediate or high cardiovascular risk and poor life expectancy from liver disease without transplantation (Only applies to the centers where active transplant surgeries are proceeding, and a patient is listed with a status sufficient that they may receive an organ in the next few weeks.)

• Postpone Testing by 2-4 months (Priority Class 2) or > 4 months (Priority Class 3)
• Myocardial Perfusion Imaging for Ischemic Heart Disease
• Stable angina: for evaluation of ischemia followup when there is no urgent revascularization plan
• 18F-FDG PET viability
• Stable chronic ischemic cardiomyopathy evaluation prior to cardiac transplant listing
• 99mTc- PYP imaging for transthyretin cardiac amyloidosis
• Heart failure where transthyretin cardiac amyloidosis is suspected
• 18F-FDG PET for sarcoidosis
• Initial evaluation: Heart block or VT and suspected cardiac sarcoidosis (Priority Class 1 or 2)
• Follow-up evaluation: Known cardiac sarcoidosis on therapy (Priority Class 2 or 3)
• 18F-FDG PET for infective endocarditis
• Follow-up evaluation: FDG PET prosthetic valve infective endocarditis
• Organ transplant
• Kidney transplant: preoperative evaluation - since most centers are not performing kidney transplants currently.
• Heart transplant: Routine evaluation for transplant vasculopathy

• Restarting your Nuclear Cardiology Lab Operations as the COVID-19 Pandemic Recedes

• Radiotracer shortage potential: April 6th 2020: NMEu advises that continued logistical difficulties create risk to security of supply of both bulk Mo-99 and Tc-99m generators, though no specific shortages are foreseen at the present (The NMEu Emergency Response Team Statement).