Cost Effectiveness

Cost effectiveness

Various studies have compared different strategies utilising MPS either as a first line or sole test in the management of patients with symptoms suggestive of IHD.

The END study (ref 1)

  • Observational study originating from the USA (over 5000 patients in each arm)

  • Comparison between MPS and direct coronary angiography (no ETT performed)

  • MPS guided arm had

    • Lower overall cost

    • Fewer coronary angiograms

    • Lower normal coronary angiogram rate

    • Less revascularisation

    • No difference in cardiac mortality rate

The EMPIRE study (ref 2)

  • Europe-wide retrospective analysis

  • Four strategies were employed using a combination of ETT, MPS and coronary angiography (CA)

  • Diagnostic and management costs were allocated to each strategy

  • Comparing ETT/CA with ETT/MPS/CA

    • No difference in cardiac event rates

    • Overall costs significantly lower using MPS to guide management

Others

  • A prospective comparison between ETT/CA and MPS/CA has been performed (ref 3)

  • Significant reduction in patients given an intermediate post-test likelihood diagnostic label

  • Significant reduction in patients undergoing CA

  • Less expensive to employ MPS, as a first line test for suspicious chest pain, in all patients apart from those with the lowest likelihood of having IHD to begin with

Conclusion

  • Strategies utilising MPS within the diagnostic algorithm are cost effective

  • A normal MPS is reassuring and reduces the need for further expensive & invasive tests.

References

  1. Shaw LJ, Hachamovitch R, Berman DS, et al. The economic consequences of available diagnostic and prognostic strategies for the evaluation of stable angina patients: An observational assessment of the value of precatheterization ischemia. J Am Coll Cardiol 1999; 33:661–9. (The END study).

  2. Underwood SR, Godman B, Salyani S, et al. Economics of myocardial perfusion imaging in Europe – the EMPIRE study.Eur Heart J 1999; 20: 157–66.

  3. Sabharwal NK, Stoykova B, Taneja AK, et al. A randomized trial of exercise treadmill ECG versus stress SPECT myocardial perfusion maging as an initial diagnostic strategy in stable patients with chest pain and suspected CAD: Cost analysis. J Nucl Cardiol 2007; 14: 174–86.

Cardiac PET

Cardiac positron emission tomography (Cardiac PET)

  • requires intravenous administration of a radionuclide on its own or tagged to a chemical

  • the radionuclide used for PET ultimately emit pairs of high energy gamma photons which move in opposite directions which can be imaged using a special equipment (PET camera)

  • PET tracers are produced either in a cyclotron or locally with a generator. Cyclotrons are very expensive (both capital and maintenance costs) and hence not every centre with a PET camera can afford it. Longer lived radionuclide like F-18 can be remotely produced and transported to other centres

Cardiac PET has a number of clinical uses including

  • identification of coronary artery disease and risk stratification

  • in patients who have an equivocal SPECT scan

  • currently in clinical practice it is mostly utilised for stress-rest myocardial perfusion imaging using Rubidium-82

  • or hibernation imaging using a combination of both 18F-FDG for metabolic viability and Rubidium-82 for perfusion

Rubidium-82 is the most commonly used cardiac PET perfusion tracer

  • It decays with a half life of 75 seconds making stress imaging possible only with pharmacological agents

  • Its short half life means lower radiation (typically 3 mSv) compared to conventional SPECT ( range 7 -15 mSv)

  • It is delivered via a generator making it available locally and it replenishes activity every 10 minutes to be delivered to the patient

  • It requires delivery every 4 weeks and the generator is expensive requiring a reasonably high throughput to justify generator cost

N-13 Ammonia is another perfusion tracer which is cyclotron produced

  • It has better tracer kinetics than Rubidium but an on-site cyclotron is necessary, due to its short half life (10 minutes), hence limiting its use

Another commonly used metabolic imaging tracer is 18F-fluorodeoxyglucose (18F-FDG)

  • this analogue combines glucose with the radioisotope Fluorine-18

  • it is used principally for myocardial viability imaging

  • Optimal uptake of 18F-FDG requires euglycaemia and the presence of insulin, which may require an oral glucose load to be given to the patient to stimulate native insulin production prior to imaging

Cardiac PET with 18F-FDG is the most sensitive means by which to identify hibernating myocardium. This is myocardium that has the potential for functional recovery if revascularised and is therefore important to distinguish from scar tissue.
The use of Cardiac PET has been increasing in recent years, particularly in the US and in some selected centres in Europe. There are both advantages and disadvantages of Cardiac PET compared to SPECT.

Advantages of Cardiac PET over SPECT

  • higher spatial and contrast resolution

  • higher diagnostic accuracy

  • lower radiation dose with Rubidium

  • exact attenuation and excellent scatter correction

  • ability to quantify absolute myocardial blood flow in ml/gm/min

  • procedure time of 30-40 minutes with Rubidium 82 tracer

  • peak stress wall motion and function assessment

  • can be combined with CT imaging to get structural information e.g. coronary calcium scoring

  • bette in patients who have more soft tissue attenuation; e.g. obese patients

Disadvantages of Cardiac PET

  • perfusion imaging almost exclusively with pharmacological stress

  • requires expensive equipment (PET camera, generator and cyclotron access)

  • limited availability

There is ongoing research into PET tracers, especially on longer acting tracers. One such agent is 18F-BMS

  • it has a high first pass extraction of 94%

  • its half life of 110 minutes allows it to be used during treadmill exercise as well as pharmacological stress

  • it is easier to distribute due to its longer half life

  • it is likely in future that it is utilised for PET myocardial perfusion studies

Utilisation of Cardiac PET will likely occur for certain patient groups in specialist centres but SPECT is likely to remain as the most utilised nuclear cardiology investigation.

References

  1. Schindler, Schelbert, Quercioli et al. Cardiac PET imaging for the Detection and Monitoring of Coronary Artery Disease and Microvascular Health. J. Am. Coll. Cardiol. Img. 2010. 3;623-640

  2. Heller, Calnon and Dorbala. Recent advances in cardiac PET and PET/CT myocardial perfusion imaging. Journal of Nuclear Cardiology. 2009. 16(6); 962-9

  3. Dilsizian et al. American Society of Nuclear Cardiology procedure guidelines (PDF). 2009.

Molecular imaging

This is an evolving field that seeks to assess in vivo biologic processes noninvasively using targeted imaging. It is hoped that it will be a useful clinical utility in all fields of Cardiology from coronary artery disease and subsequent ischaemia through to global inflammatory processes such as myocarditis. The aims of molecular imaging are:

  • to detect metabolic changes that reflect disease allowing early identification and treatment of disease

  • as a tool in assessing responses to therapeutic interventions

There are some requirements for successful molecular imaging these are:

  • Identification of a target molecule of interest which must be expressed in large numbers at the site of interest

  • construction of a molecular contrast agent which typically consists of two components;

  • A ligand; a molecule that is able to bind to the target molecule of interest retaining the contrast agent at this site, e.g. an antibody or peptide

  • A contrast element which in the case of SPECT or PET imaging is a radionuclide tracer which can then be detected and quantified

Current research has been focusing on the following various disease processes, which are key to diseases affecting the heart. These are:

  • Angiogenesis- formation of new blood vessels; important in repair from ischaemia and prediction of plaque rupture. It is thought that the degree of angiogenesis may impact on patient prognosis, with impaired angiogenesis conferring a poorer prognosis

    • Targets- VEGF (vascular endothelial growth factor) and αvβ3 integrin

    • Contrast agents- 64Cu-6DOTA-VEGF121, 111In-RP748 and 99mTc-RAFT-RGD, 18F-Galakto-RGD

  • Inflammation- integral part of healing process

    • Targets-myosin heavy chainsand tenascin-C

    • Contrast agents- 111In-antimyosin antibodies, 99mTc-labeled monoclonal antibody fragments and111In-labeled antitenascin-C

  • Apoptosis – programmed cell death, increased levels of apotosis in myocardial infarction, heart failure and cardiomyopathies

    • Targets-annexin V and caspase 3

    • Contrast agents- 99mTc-labeled annexin V and a caspase-3 inhibitor; 18F-WC-II-89

  • Ventricular remodelling- complex changes involving other disease processes that result in alterations in the tissues of the damaged area

    • Targets- matrix metalloproteinases and factor XIII

    • Contrast agents- 111In-RP782, 99mTc-RP805 and 111In-DOTA-FXIII

  • Atherosclerosis- involves inflammation and plaque formation within arteries. Plaques with an increased metabolism due to an increase in inflammatory cells, especially macrophages have a higher risk of rupture. Could be used to assess treatment effects such as statin therapy.

    • Targets- macrophages

    • Contrast agents- 18F-FDG

A method termed indirect molecular imaging has emerged recently in animal models. This is a complex technique but aims to avoid having to develop a different ligand for each area of study.

The basis of this method is:

  • a gene of interest (a reporter gene) is introduced into the cell nucleus

  • it then undergoes the processes of transcription and translation, utilising the cells own machinery, to produce proteins

  • these proteins then interact with a complimentary reporter probe labelled with a radioactive nucleotide

  • this interaction can take various forms depending upon the protein generated by the reporter gene, for example the encoded protein may be a cell surface receptor to which the probe may then bind.

However, work utilising this approach is still in the early phases in animal models and requires further identification of the molecular processes of interest to utilise this technique.

Molecular imaging is likely to represent an ongoing area of expansion; it should allow us to better understand pathological processes at a molecular level which hopefully will ultimately lead to improved treatments and prevention of the end stage effects of the underlying disease.

References

1. Morrison and Sinusas . Advances in radionuclide molecular imaging in myocardial biology. Journal of Nuclear Cardiology.2010. 17(1);116-34
2. Kate, Sijbrands, Valkema et al. Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques? Journal of Nuclear Cardiology. 2010. 17(5); 897-912