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European Nuclear Medicine Guide
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European Nuclear Medicine Guide
Chapter 2.3

Cardiac Function/ERNA

2.3.1 Radiopharmaceuticals

  • 99mTc-labelled red blood cells (RBCs)
  • 99mTc-labelled human serum albumin (HSA)
  • [99mTc]pertechnetate

2.3.2 Uptake mechanism / biology of the tracer

In vivo labelling: injection of a reconstituted solution of a Sn2+ agent followed by injection of sodium [99mTc]pertechnetate 20-30 min later.

In vitro labelling: a small volume (1-10mL) of blood, anticoagulated with heparin or acid citrate dextrose (ACD) solutions, is incubated with a reconstituted Sn2+ agent for 5-10 min in a closed vial to avoid exposure to oxygen. When stannous citrate is used for pre-tinning of the RBCs, the incubation is followed by the addition of 0.1% sodium hypochlorite and ACD solution. In this case, free tin in the plasma may be removed as a tin citrate complex. After incubation, the cells are separated by centrifugation, the plasma is removed, and the RBCs are incubated with 99mTc-pertechnetate for 5-20 min. After incubation, unbound activity is washed away by addition of saline and centrifugation. The supernatant is removed, and the red cells are resuspended in saline before re-injection. With the Ultratag method, the centrifugation steps are not required.

In vivo/in vitro labelling: the injection of a stannous agent is followed 20-30min later by withdrawal of 3-10mL of pre-tinned blood through a cannula into a shielded syringe containing an anticoagulant and the required amount of [99mTc]pertechnetate. The blood is mixed with the [99mTc]pertechnetate and allowed to incubate for 10-20 min. The unbound activity may be washed by centrifugation before reinjection or, alternatively, the radiolabelled RBCs can be reinjected without the washing step. Technetium-99m radiolabelled human serum albumin (HSA) is an alternative to radiolabelled RBCs [17,18].

2.3.3 Indications

Equilibrium Radionuclide Angiocardiography (ERNA) can be used to assess:

  • regional and global wall motion;
  • cardiac chamber volumes and morphology;
  • ventricular systolic and diastolic function indices including LV and right ventricular (RV) EF;
  • response of above parameters to exercise or other interventions and stroke volume ratios.
  •  

2.3.4 Contra-indications

  • The only absolute contra-indication is pregnancy.
  • Breast feeding should be interrupted for 12 h following the examination [3].  Breast milk could be collected and stored beforehand, in order to be provided to the infant during the interruption period.

2.3.5 Clinical performances

Assessment of LV function and volumes has important prognostic value and are powerful predictors of long-term outcome after acute myocardial infarction. Moreover, in patients with known or suspected heart failure, ERNA can help distinguish systolic from diastolic causes of congestive heart failure. Evaluation of LVEF and LV volumes has important prognostic significance, and evaluation of the function of the RV has a prognostic value. In these patients, initial assessment of LV and RV function is considered a class I indication.

Identification of patients who could benefit from an internal cardioverter defibrillator or from cardiac resynchronization therapy is other important issue, and radionuclide imaging is one of the techniques that can provide an accurate assessment of LVEF. Moreover, ERNA presents the advantage of high inter-operator reproducibility. The evaluation of cardiac function in patients undergoing chemotherapy is considered a fundamental parameter for monitoring cardiotoxicity induced by cytotoxic drugs which can cause depressed LVEF and progressive heart failure.

ERNA has an important role in the evaluation of Patients with Chagas’ myocarditis/ cardiomyopathy and assessment of ventricular function in patients with valvular heart disease such as aortic regurgitation.

Assessment of RV function is recognized to be important in subgroups of patients including those with arrhythmogenic RV, lung transplant candidates, and after myocardial infarction (MI), possibly including RV infarction, with high prognostic value of demonstrating RV dysfunction.

Finally, candidates for and monitoring after heart transplantation need an accurate determination of LVEF which is used to determine the right time for referral to heart transplantation and for monitoring post-transplant patients.

2.3.6 Activities to administer

For adults, the range of the administered activities is 555-1110 MBq for any 99mTc-tracer. In paediatric nuclear medicine, the activities should be modified according to the EANM paediatric dosage card (https://www.eanm.org/publications/dosage-calculator/). The minimum recommended activity is 80 MBq.

2.3.7 Dosimetry

The effective doses per administered activity are [3]:

  • 99mTc-labelled red blood cells (RBCs): 7 µSv/MBq
  • 99mTc-labelled human serum albumin: 11 µSv/MBq
  • [99mTc]pertechnetate: 13 µSv/MBq

The range of the effective doses for the suggested activities is: 3.9-14.4 mSv.

Caveat

“Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but  it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."

2.3.8 Interpretation criteria/major pitfalls

Interpreting ERNA requires both visual and quantitative analyses.

The preferred projection is the best-septal (a 30-45° modified Left Oblique Orientation (LOA) projection) that best demonstrates left/right ventricular separation and left ventricular/left atrial separation. The other views are left lateral projection and anterior projection.

Computer-based analysis of ERNA studies can accurately evaluate ventricular volumes. By using equilibrium technique, a quantitative measurement of regional left ventricular function can be obtained with different methods. The more utilized method for the assessment of regional function is the phase and amplitude analysis based upon the onset, timing and extent of contraction. The use of SPECT imaging can be needed to better localize RV.

Major pitfalls include:

  • RBC labelling: when an in vitro method is used, a fail-safe procedure must be implemented to assure that administration of labelled cells to the wrong patient is prevented. Moreover, certain medications and disease processes will decrease labelling efficiency and reduce the target-to background ratio.
  • Images acquisition: the EF may be inaccurately calculated by inadequate separation of the LV from other cardiac structures.
  • Gating errors due to a poor ECG signal (atrial fibrillation or ventricular ectopy).
  • Inadequate counts/frame may compromise image interpretation as well as decrease the statistical reliability of quantitative measurements.
  • Processing errors:
    • Inclusion of non-ventricular activity or exclusion of ventricular activity from ventricular regions of interest (ROIs);
    • Inclusion of structures such as the spleen or the descending aorta in the background ROI.

2.3.9 Patient preparation

No special preparation is required for a resting ERNA. It is not necessary to withdraw any medications. The electrodes used for cardiac gating must be placed on the thorax to ensure an optimal ECG signal.

For an exercise ERNA, the patient should be fasting for at least 3-4h before the study. Exercise stress is generally preferred. Patients who are unable to exercise may undergo pharmacologic stress testing. Medications that may alter the heart rate response may be withdrawn unless medically contraindicated or the efficacy of the medication is being tested by the exercise test [18]. Continuous, preferably 12 - lead ECG monitoring must be performed throughout all phases of the stress study.

2.3.10 Methods

The detailed recommendations regarding the modality of acquisition of radionuclide ventriculography are available in the EANM/ESC guidelines for radionuclide imaging of cardiac functioning  EANM/ESC guidelines for radionuclide imaging of cardiac function and in the SNMMI Procedure Standard/EANM Guideline for Gated Equilibrium Radionuclide Angiography [17,18].