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Inside the myocardial wall: do we have enough imaging power to assess the transmural distribution of ischemia and scar?

An article from the e-journal of the ESC Council for Cardiology Practice

In patients with myocardial infarction, contrast MRI has an emerging role as gold standard for the transmural characterisation of viable myocardium that has not yet entered clinical cardiology for several reasons, such as cost and availibility.



As a consequence, the transmural extent of a scar is not yet a clinical question that allows the use of cMRI as a first line diagnostic tool. In the meantime, preliminary data suggest that beyond ischemia, Myocardial perfusion scintigraphy (MPI) reflects enough “transmurality” in the assessment of viability.

Background

Despite the fact that quantitative estimation of transmural blood flow is possible in experimental preparations, it is not yet possible on a clinical basis to measure the transmural distribution of hypoperfusion or viable myocardium in patients.

Methods for estimating infarct size in patients

In clinical practice, the most diffuse approaches to estimating infarct size – electrocardiographic techniques, enzyme release and wall motion abnormalities – have major limitations. None of these procedures provides an estimate of the transmural distribution of infarcted myocardium precise enough to be clinically useful.

Myocardial perfusion scintigraphy (MPI) has provided important diagnostic and prognostic information in the field of ischemia and viability, and the semiquantitative evaluation of severity and extension of ischemia has been shown to have an incremental value in the diagnosis of coronary artery disease. MPI provides an excellent estimation of infarct size that, when combined with volume measurements and regional wall motion analysis, identifies high risk patients and predicts reversible dysfunction after revascularisation (1). However, despite the availability of an extensive database, MPI does not provide a transmural identification of ischemia and scar. In fact, especially in infarcted walls object size falls below the resolution of the gamma camera, and the partial volume effect limits the attribution of scar to different myocardial layers.

Magnetic resonance imaging (MRI) is a clinical standard in the assessment of biventricular function and mass. Moreover, experimental and clinical studies show that magnetic resonance can directly visualie healed myocardium with delayed contrast imaging (cMRI). The high spatial resolution of cMRI and the high contrast gradient between scar and normal tissue allow the assessment of the transmural extent of fibrosis (2).

Positron Emission Tomography (PET) has improved its intrinsic resolution and may allow with 3-D imaging a quantification of subendocardial and subepicardial myocardial blood flow and the relative coronary flow reserves using (15)O-labeled water. In a recent experimental study (3), Rimoldi et al showed that despite the partial volume effect, dynamic PET measurements allow regional estimates of the transmural distribution of MBF over a wide flow range, and that PET subendocardial and subepicardial flow reserves were in good agreement with the microsphere values. In the field of multidetector-row computed tomography no data is available about the transmural assessment of blood flow in humans.

Does MPI reflect any transmural information?

Due to its excellent spatial resolution, cMRI may provide the assessment of the transmural extent of hypoperfusion that no other method can offer as “image”. Thus, if available data suggests that cMRI is superior to any other currently used methods, which is the meaning of presence, location and spatial extent of a myocardial infarction studied by MPI? Clinical and experimental data suggest that MPI and cMRI detect transmural myocardial infarcts at similar rates, and also that MPI does not detect 50% of subendocardial infarcts that are identified by cMRI (4).

More recently, 99mTc tetrofosmin injected at rest after nitrates have been, demonstrated to inversely correlate with the transmural extent of scar in patients with previous myocardial infarction and severe left ventricular dysfunction (5) and reduce the percentage of MPI false viable segments to 22%. Thus, in line with previous observations that nitrates ameliorate the diagnostic and the prognostic approach to tissue viability, they also allow a better correlation between regional uptake and the distribution of cMRI hyperenhancement.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

Conclusion:

In patients with myocardial infarction, contrast MRI has an emerging role as gold standard for the transmural characterisation of viable myocardium, but it has not yet entered clinical cardiology for several reasons:

  • cost of a cMRI is not negligible and is higher than that of an MPI;
  • cMRI requires specific cardiological knowledge that is not available in all MRI centers;
  • availability of “cardiac” MRI devices is still low;
  • although interesting and innovative, cMRI results are preliminary and obtained in selected study groups;
  • cMRI data are limited to viability and for technical reasons do not extend to the transmural characterisation of transient ischemia while the detection of stress perfusion defects caused by coronary artery disease is the keypoint of MPI.
  • the incremental diagnostic and prognostic value of cMRI has not been evaluated.

As a consequence, the transmural extent of a scar is not yet a clinical question that allows the use of cMRI as a first line diagnostic tool.

This question will expand and the exact definition of scar through an imaging approach will contribute to rewrite significant parts of the pathophysiology of coronary artery disease and to understand some unsolved issues in the field of non-responders to medical treatment, revascularisation or even resynchronisation. In the meantime, preliminary data obtained in patients with previous myocardial infarction studied by different imaging protocols suggest that beyond ischemia MPI reflects enough “transmurality” in the assessment of viability, especially when 99mTc tracers are correctly associated with nitrates. Finally, experimental data obtained with PET and labeled water (3) and the possibility to use “tracer” adenosine (6) are also encouraging toward the characterisation of the transmural extent of viable myocardium.

References


1. Flotats A, Carrio I, Estorch M, Berna L, Catafau AM, Mari C, Ballester M. Nitrate administration to enhance the detection of myocardial viability by technetium-99m tetrofosmin single-photon emission tomography. Eur J Nucl Med. 1997; 24:767-773
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9211763&query_hl=2&itool=pubmed_docsum

2. Wu E, Judd RM, Vargas JD, Klocke FJ, Bonow RO, Kim RJ. Visualization of presence, location and transmural extent of healed Q-wave and non-Q-wave myocardial infarction. Lancet 2001; 357, 21-28.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11197356&query_hl=1&itool=pubmed_docsum

3. Rimoldi O, Schafers KP, Boellaard R, Turkheimer F, Stegger L, Law MP, Lammerstma AA, Camici PG. Quantification of subendocardial and subepicardial blood flow using 15O-labeled water and PET: experimental validation. J Nucl Med. 2006; 47, 163-172. 
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16391201&query_hl=3&itool=pubmed_docsum

4. Wagner A, Mahrholdt H, Holly TA, Elliot MD, Regenfus M, Parker M, Klocke FJ, Bonow RO, Kim RJ, Judd RM. Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study. Lancet  2003; 361, 374-379
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12573373&query_hl=5&itool=pubmed_DocSum

5. Giorgetti A, Pingitore A, Favilli B, Kusch A, Lombardi M, Marzullo P. Baseline/postnitrate tetrofosmin SPECT for myocardial viability assessment in patients with postischemic severe left ventricular dysfunction: new evidence from MRI. J Nucl Med. 2005; 46,1285-1293.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16085584&query_hl=7&itool=pubmed_docsum

6. Lauer T, Loncar R, Deussen A. Tracer  adenosine:  a novel myocardial flow marker; J Nucl Med 2003; 44, 641-648. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12679411&query_hl=9&itool=pubmed_docsum

 

VolumeNumber:

Vol4 N°24

Notes to editor


Paolo Marzullo, MD, FACC, FESC.
Nucleus Member and past Chairman Working Group Nuclear Cardiology.
Director, Nuclear Cardiology, CNR Pisa, Italy.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

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