Viability Studies - Comparison of Techniques

Abstract

Ischemic cardiomyopathy is one of the most common causes of congestive heart failure. Despite multiple therapeutic options, morbidity and mortality remain high. Revascularization is one of the best options to improve ejection fraction and survival in patients with hibernating myocardium. This article discusses the role of positron emission tomography (PET), single-photon emission computed tomography (SPECT), dobutamine stress echocardiography (DSE), and magnetic resonance imaging (MRI)-based viability studies and their comparative evaluation.

Correspondence
Dmitriy Kireyev, MD, FACC, Cambridge Health Alliance, Whidden Memorial Hospital, 103 Garland Street, Everett, MA 02149. E: dkireyev@cha.harvard.edu
Citation
American Heart Hospital Journal 2011;9(2):107-11
DOI
https://doi.org/10.15420/ahhj.2011.9.2.107

More than 20 million people worldwide are estimated to have been diagnosed with congestive heart failure (CHF).1 In the US, more than 5.8 million cases have been reported, with approximately 670,000 new cases each year.2 Heart failure is a diagnosis associated with high morbidity and mortality. CHF can be categorized as either systolic (reduced left ventricular ejection fraction) or diastolic (preserved ejection fraction) heart failure. Systolic heart failure may be due to multiple causes, one of these being dilated cardiomyopathy which can develop secondary to ischemic myocardium.

Medical therapy of CHF due to systolic dysfunction has evolved significantly during the last several decades. Beta-blockers, such as bisoprolol, carvedilol, and metoprolol XL/CR, were shown to improve mortality and reduce hospitalizations in patients with systolic heart failure.3–7 Angiotensin-converting enzyme inhibitors and some angiotensin receptor blockers have been demonstrated to significantly decrease morbidity and mortality in patients with CHF.8–14 Competitive antagonists of aldosterone, such as spironolactone, as well as the aldosterone receptor blocker eplerenone further decrease mortality when added to standard therapy for CHF.15,16 Cardiac resynchronization therapy improves symptoms and quality of life and decreases mortality in patients with CHF and cardiac dyssynchrony.17

The most common cause of CHF is ischemic cardiomyopathy (ICM).18 A significant percentage of patients (more than 50 % in some studies) with ICM will have decreased ejection fraction but viable myocardium.19,20 Revascularization remains one of the best treatment options in such cases.21

Multiple studies have shown an improvement in left ventricular ejection fraction and functional status and better long-term prognosis in patients undergoing revascularization based on the presence of viable myocardium.22–25 The outcome after revascularization is related not only to the presence, but also to the extent of viable myocardium, thus making it especially important to quantify the amount of viable myocardium so as to properly assess the risks and benefits of potential interventions.26–28 Although multiple retrospective trials and meta-analyses showed the benefit of using viability studies, one of the more recent substudies of the Surgical treatment for ischemic heart failure (STICH) trial did not show the same.

Even though presence of viable myocardium, as assessed by single-photon emission computed tomography (SPECT) or dobutamine echocardiography, was associated with an increased probability of survival, this finding was not found to be statistically significant after adjustment for multiple baseline factors for mortality.29 However, the analyzed subgroup represented fewer than 50 % of patients from the study and there was no randomization of the patients. The assessment of viability was performed by two commonly used techniques. However, neither of them is considered a gold standard of viability evaluation and, since there was no randomization and double-blinded control, we cannot conclude with certainty that the result of viability studies did not influence the final treatment strategy.

Currently, positron emission tomography (PET), SPECT, dobutamine stress echocardiography, and magnetic resonance imaging (MRI) are among the most common methods of assessment of viability in ICM.

Positron Emission Tomography

The extent of myocardial viability using PET may be evaluated by comparison of myocardial perfusion and metabolism in segments with balanced reduction of function and perfusion. Myocardial perfusion is evaluated with a flow tracer using either 13N-ammonia or rubidium-82. Metabolism is evaluated with cellular 18F-fluorodeoxyglucose (FDG) uptake. Positive 18F-FDG uptake indicates cellular viability. The presence of a mismatch pattern between cellular viability and myocardial perfusion is considered to show areas of the heart where hibernating myocardium is present and myocardial function may be improved if the blood supply is restored.

PET is considered to be the gold standard for the evaluation of myocardial viability.30 Studies have demonstrated the importance of FDG-PET for morbidity and mortality benefit in patients undergoing revascularization. Revascularization of patients with viable myocardium is reported to improve patient prognosis in 55 % and left ventricular ejection fraction in 27 % of patients with ICM.31 Revascularization decisions incorporating myocardial viability evaluation have significantly improved mortality and prognosis ofpatients with ICM.32

Single-photon Emission Computed Tomography

Myocardial viability may be assessed by analysis of myocardial uptake of thallium-201, technetium-99m sestamibi, or technetium-99m tetrofosmin by SPECT. Myocardium is considered viable if the uptake of the above-mentioned radionuclide tracer is more than 50–60 % in the dysfunctional myocardium.33,34

Thallium-201 is a radioactive substance that has cellular uptake similar to that of potassium. Thallium uptake by the myocardial cell is partially an active process involving the sodium/potassium adenosine triphosphatase (Na/K ATPase) pump and requires both myocardial cell integrity and good perfusion for delivery to different areas of the heart.

In 1977, it was suggested that stress-induced thallium defects could normalize (‘redistribute’) on images repeated in several hours.35 This was considered to be useful in the differentiation of transient perfusion abnormalities related to ischemic tissue versus infarct. Redistribution after four hours can overestimate the extent of myocardial necrosis. Reinjection of a smaller dose of thallium-201 immediately before the redistribution images are taken improves the detection of viable myocardium.36 This method has been shown to detect viability in 50–70 % of territories that would be necrotic on standard thallium redistribution imaging.36–38 Viability studies performed with the use of technetium-99m sestamibi and technetium-99m tetrafosmin are reported to be comparable with studies performed using thallium-201.34,39

Although FDG-PET scanning is considered to be the gold standard for assessing myocardial viability, its widespread use is limited by the high cost of the imaging system and tracers. Bonow et al. evaluated the compatibility of viability assessment by both FDG and thallium-201-based methods.41 Four hundred thirty-two myocardial segments were analyzed from comparable transaxial tomograms. One hundred sixty-six segments were found to be irreversible on the standard four-hour redistribution using thallium. FDG uptake occurred in 121 of these regions (73 %). When using the thallium reinjection method only 78 of the 166 regions (47 %) showed thallium activity. This is significantly lower than FDG uptake images obtained by PET. However, in subgroup analysis the areas with severe thallium reuptake defect after reinjection (<50 % of peak activity) showed uptake in 51 % of the segments, which is consistent with results obtained from FDG uptake in the same group. Irreversible defects with mild or moderate reduction in thallium activity represent viable myocardium in a majority of cases as was confirmed by FDG uptake analysis. The superiority of PET viability studies was also shown by Alexanderson et al.41 Their analysis showed that PET has a 30 % higher viability detection rate when compared with thallium SPECT redistribution.

Myocardial FDG uptake evaluation using SPECT has been suggested as a practical alternative to PET for detecting myocardial viability.42 FDG-SPECT requires higher collimator efficiency to assess uptake of 18F-FDG. FDG-SPECT showed concordance with PET images in 90 % of the cases, with the kappa test showing good agreement between the two tests. Even though FDG-SPECT is inferior to FDG-PET in assessing myocardial viability and provides inferior imaging characteristics, it is more widely available, provides good concordance (90 %), and can thus be used as a reliable alternative when PET is not available.

Dual-isotope simultaneous acquisition SPECT(DISA-SPECT) using 18F-FDG as metabolic tracer and technetium-99m sestamibi as flow tracer can be used as an alternative method for the evaluation of myocardial viability. This method permits the assessment of both myocardial perfusion and glucose utilization in one imaging test. This method was shown to have myocardial viability and wall motion abnormality evaluation that is similar to PET and MRI techniques.43 However, in a more recent study using a thorax–heart phantom, the DISA-SPECT method failed to provide correct results for all the inserts in the cardiac–thoracic phantom whileFDG-PET correctly identified two non-viable myocardium inserts.44 PET had significantly higher sensitivity, with the difference in sensitivity between both tests being a factor of 2.5. These differences were attributed to the lower resolution with SPECT images and higher septal penetration with PET images.

Thus the literature supports the superiority of FDG-PET imaging for assessing myocardial viability over SPECT. FDG-PET has higher resolution, sensitivity, and specificity for evaluation of viable myocardium when compared with SPECT and DISA-SPECT.40,41,44

Dobutamine Stress Echocardiography

Dobutamine stress echocardiography is another method being used to assess myocardial viability. It evaluates the inotropic reserve of dysfunctional, but viable myocardium after administration of low-dose dobutamine. The prevalence of contractile reserve during low-dose dobutamine echocardiography in patients with coronary artery disease (CAD) and left ventricular dysfunction is independent of the angiographic extent and severity of CAD.45,46 The increase in contractility induced by low-dose dobutamine infusion in dysfunctional viable myocardium supplied by nearly occluded vessels occurs even in the absence of a significant increase of blood flow.45,47

The positive predictive value of dobutamine echocardiography viability study and recovery prognosis after revascularization is significantly increased with biphasic response: improvement of contractility at a low dose, due to use of contractile reserve, and worsening at a high dose, due to subendocardial ischemia.47,48 When compared with thallium-201 SPECT and FDG-PET myocardial viability assessment, dobutamine echo required a higher percentage of viable myocardium proven by histology in the affected myocardial segment to show response.50 While nuclear imaging methods of assessment of viability are more sensitive, dobutamine echocardiography is reported to be more specific for the detection of viable myocardium.51

Magnetic Resonance Imaging

More recently, cardiac MRI has been proposed as an effective modality for the assessment of myocardial viability. Three variables have been assessed for the evaluation of cardiac viability using MRI. Evaluation of end-diastolic wall thickening has high sensitivity but low specificity for the evaluation of myocardial viability.52 Unfortunately, this method is reliable only four months after the myocardial infarction. Assessment of contractile reserve provided further insight for viability evaluation. Contrast-enhanced MRI for the detection of myocardial viability along with metabolic imaging techniques, such as phosphorus-31 magnetic resonance (MR) spectroscopy and sodium-23 MR imaging, give another approach to viability evaluation.52 A combined review of studies showed that sensitivity and specificity of viability evaluation by MRI were 91 % and 45 % using end-diastolic wall thickening, 72 % and 82 % using dobutamine stress MRI, and 84 % and 73 % using contrast-enhanced MRI.53

Ansari et al. showed that hyperenhancement evaluation by cardiac MR correlated well with thallium-201 uptake by SPECT for evaluation of non-viable myocardium in all regions except for the inferoseptal region which showed decreased correlation, most probably secondary to increased diaphragmatic attenuation.54

Gutberlet et al. evaluated viability assessment in patients using end-diastolic wall thickness, delayed-enhancement MRI, stress MRI with the use of dobutamine, and thallium-201 SPECT.55 Myocardial recovery at six months after coronary artery bypass graft surgery was used as a gold standard for the evaluation.

Delayed enhancement on cardiac MRI was associated with the highest sensitivity (99 %), specificity (94 %), and negative predictive value (94 %). MRI end-diastolic wall thickness, wall motion analysis, and thallium SPECT were associated with lower sensitivity (96 %, 88 %, 86 %), specificity (35 %, 90 %, 68 %), and negative predictive value (57 %, 56 %, 44 %), respectively.

Several studies have compared MRI with FDG-PET, which is considered the gold standard for the detection of myocardial viability. An excellent correlation between the two methods was found.56 Gadolinium MRI was found to have 96 % sensitivity and 84 % specificity when compared with FDG-PET.

Conclusions

ICM remains one of the most common causes of CHF. Despite the development of multiple pharmacological and therapeutic options, mortality and morbidity continue to be high. Myocardial revascularization is one of the most effective treatment modalities in a properly chosen patient population. Viability studies remain a cornerstone of risk stratification for patients prior to referral for coronary artery bypass surgery. With the aging of the population and increase in the amount of comorbidities of patients referred for surgery, a proper evaluation is increasingly important to determine the best possible treatment strategy for CHF patients.

PET scan is considered to be the gold standard for viability evaluation. However, the higher cost and lack of availability of this technique have limited its use in the past. Quantitative coronary blood flow determination by PET and calculation of regional coronary flow reserve can further enhance myocardial perfusion assessment for comparison with metabolism.57

MRI is another method for the evaluation of viable myocardium. Its sensitivity and specificity for the detection of viable myocardium are similar to PET. With the more widespread use of this technology it appears to be a reasonable alternative to PET.

SPECT using thallium-201 and dobutamine echocardiography appear to be inferior to PET and MRI in sensitivity and specificity of diagnosing viable myocardium. However these tests remain a practical alternative to both PET and MRI and are currently widely used throughout the US.

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