With hybrid SPECT/CT and PET/CT systems a prospectively gated calcium score scan can be acquired along with the MPI or the CTAC obtained during PET–CT or SPECT–CT MPI can be visually assessed for coronary artery calcification with good accuracy.24,25 Several studies wherein subjects underwent both a CAC score study and MPI (at the same setting or at different settings) have demonstrated that subjects with normal MPI may have extensive underlying calcified atherosclerosis, and this finding may influence physicians to prescribe aspirin and lipid-lowering agents.26 The frequency of ischemia in subjects with Agatston calcium score of >400 is high (>20%)27–31; a myocardial perfusion study is considered appropriate among individuals with CAC score >400 or among individuals with high CHD risk and CAC score 100 to 400 independent of symptoms.32 As with CAC score, investigators33 have evaluated the diagnostic and prognostic value of a zero CAC score in conjunction with stress SPECT MPI in patients presenting to the emergency room with chest pain. In that study, 0.8% of patients had an abnormal MPI (5/625 patients, four of whom had no CAD on subsequent invasive angiography), and 0.3 event rate (mildly elevated troponin, no cardiac death) over a mean follow-up of 7 months. These authors33 concluded that most of the patients with chest pain in the ED have a calcium score of 0, which predicts both a normal stress SPECT result and an excellent short-term outcome. A recent meta-analysis by Bavishi et al.34 confirmed that zero to low CAC scores were infrequently associated with ischemia, but there was a wide variance in the frequency of ischemia among patients with intermediate to high CAC scores (Tables 25-1 and 25-2).
Table 25-1A Listing of Studies That Reported on the Prevalence of CAC Score and Myocardial Ischemia ||Download (.pdf) Table 25-1 A Listing of Studies That Reported on the Prevalence of CAC Score and Myocardial Ischemia
|First Author ||Year of Publication ||Sample Size ||Patient Characteristics ||Age (years) ||Male (%) ||HTN (%) ||DM (%) ||HL (%) ||CAC Categories ||Ischemia Prevalence (%) |
|Anand ||2004 ||220 ||Asymptomatic, suspected CAD ||56 ± 11 ||72 ||35 ||30 ||30 ||100–399, ≥400 ||30 |
|Anand ||2006 ||180 ||Asymptomatic, Type II DM ||53 ± 8 ||61 ||22 ||100 ||62 ||≤10, 11–100, 101–400, 401–1000, >1,000 ||31.7 |
|Blumethal ||2006 ||260 ||Siblings of premature CAD ||51 ± 8 ||38 ||60 ||14 ||38 ||0, 1–10, 11–100, 101–399, ≥400 ||18.8 |
|Chang ||2015 ||946 ||Suspected CAD ||58 ± 9 ||75 ||50 ||10 ||57 ||0–10, 11–100, 101–400, ≥400 ||10.9 |
|Estevez ||2008 ||80 ||Symptomatic, suspected CAD ||62 ± 15 ||39 ||80 ||30 ||38 ||0, >0 ||15.5 |
|Fathala ||2011 ||157 ||Suspected CAD ||64 ± 10 ||60 ||18 ||17 ||16 ||0, >10 ||31.8 |
|Ghardi ||2013 ||462 ||Known or suspected CAD ||63 ± 11 ||68 ||53 ||17 ||40 ||0, >0 ||22.9 |
|He ||2000 ||411 ||Suspected CAD ||53 ± 8 ||69 ||39 ||6 ||54 ||0, 1–10, 11–100, 101–399, ≥400 ||19.7 |
|Ho ||2007 ||703 ||Suspected CAD ||59 ± 9 ||79 ||48 ||7 ||69 ||0–10, 11–100, 101–400, 401–1000, >1000 ||7.4 |
|Moser ||2003 ||102 ||Asymptomatic, suspected CAD ||NR ||NR ||NR ||NR ||NR ||0–100, 101–400, ≥400 ||18.6 |
|Nishida ||2005 ||83 ||Symptomatic, suspected CAD ||68 ||66 ||63 ||27 ||48 ||0, >0 ||42.2 |
|Piers ||2008 ||531 ||Suspected CAD ||55 ± 11 ||57 ||57 ||12 ||41 ||<10, 10–99, 100–399, ≥400 ||13.9 |
|Ramakrishna ||2007 ||835 ||Suspected CAD ||55 ± 10 ||77 ||42 ||14 ||67 ||0, 1–10, 11–100, 101–400, >400 ||8.3 |
|Rozanski ||2007 ||1153 ||Suspected CAD ||58 ± 10 ||74 ||38 ||8 ||65 ||0, 1–9, 10–99, 100–399, 400–999, ≥1,000 ||5.6 |
|Rosman ||2006 ||126 ||Asymptomatic, Suspected CAD ||59 ± 11 ||67 ||39 ||10 ||72 ||0, 1–99, 100–399, 400–999, ≥1000 ||18.3 |
|Schenker ||2008 ||621 ||Suspected CAD patients ||61 ± 11 ||40 ||74 ||28 ||54 ||0, 1–399, ≥400 ||28.8 |
|Schepis ||2007 ||77 ||Suspected CAD Patients ||66 ± 9 ||62 ||73 ||18 ||NR ||≤10, 11–100, 101–400, 401–1,000, ≥1000 || |
|Scholte ||2008 ||100 ||Asymptomatic, Type II DM ||53 ± 10 ||65 ||51 ||100 ||53 ||0, 1–10, 11–100, 101–400, 401–1000, ≥1000 ||23 |
|Seyahi ||2011 ||35 ||Renal Transplant ||37 ± 11 ||67 ||81 ||6 ||NR ||101–400, ≥400 ||17.1 |
|Yao ||2004 ||73 ||Suspected CAD ||53 ± 11 ||NR ||NR ||NR ||NR ||0, 1–10, 11–100, 101–399, ≥400 ||42.5 |
Table 25-2Pooled Prevalence and Odds Ratio for Ischemia by CAC Categories ||Download (.pdf) Table 25-2 Pooled Prevalence and Odds Ratio for Ischemia by CAC Categories
|CAC Categories ||Patients (n) ||Pooled Prevalence of Ischemia (%) ||Range of Ischemia (%) ||Pooled Odds Ratio (95% CI) |
|0 ||487 ||6.6 ||0.0–24.1 ||Reference |
|1–100 ||529 ||8.5 ||2.1–50.0 ||1.7 (1.04–8.2) |
|101–399 ||513 ||10.5 ||4.0–63.6 ||3.3 (1.4–8.2) |
|≥400 ||594 ||23.6 ||12.4–57.1 ||6.9 (3.5–13.4 |
Indeed, the broad range of CAC scores27–31 among patients with both normal and abnormal perfusion scans in multiple studies, supports the concept that presence of calcified coronary atherosclerosis does not necessarily predict ischemia. Moreover, in subjects without overt CAD, the degree of CAC showed no relation35 or a weak inverse relation to peak hyperemic myocardial blood flow and coronary flow reserve and direct relation to coronary vascular resistance.36–38 The results of these studies suggest that CAC score and coronary microvascular function may provide biologically different information and could be complementary for risk assessment.
When combined with SPECT or PET MPI, CAC score provides independent and complementary information about risk of death or myocardial infarction.30,31 In a previous SPECT study, including a lower-risk cohort with some asymptomatic subjects, and normal MPI, calcium scores did not show an incremental prognostic value over MPI over a mean follow-up of 32 months.39 In contrast, with a longer follow-up (mean follow-up of 6.9 years), Chang et al.30 demonstrated that individuals with high calcium score had greater annualized cardiac event rates (3%), despite a normal MPI (Fig. 25-5). The addition of a CAC score to 82Rb perfusion data provided incremental prognostic information in patients with both ischemic and nonischemic perfusion studies.40 These combined data supports the concept that while a normal relative MPI may indicate excellent short-term prognosis a high CAC score may indicate a worse intermediate-term prognosis despite a normal MPI.
Adjusted annualized total cardiac death, MI, and coronary revascularization (A) and all-cause death/MI (B) event rates based on CACS and SPECT results. CACS, coronary artery calcium score; MI, myocardial infarction. (Reproduced with permission from Chang SM, Nabi F, Xu J, et al. The coronary artery calcium score and stress myocardial perfusion imaging provide independent and complementary prediction of cardiac risk. J Am Coll Cardiol. 2009;54(20):1872–1882.)
Hybrid Coronary CTA and MPI
Imaging coronary atherosclerosis and its functional consequences with hybrid SPECT/CT and PET/CT devices in a single or a sequential study is now a reality. When performed on the same day, coronary CTA is typically performed after completion of stress MPI, so that beta-blockers can be administered to slow the heart rate for the coronary CTA without affecting ischemia assessment on MPI. Radionuclide and coronary CTA images can be interpreted independently or together using one of several software options to fuse the images.
The relationship between anatomic assessment of CAD and functional assessment of perfusion is complex. Lesion severity as assessed by coronary angiography does not account for the degree of endothelial dysfunction or the effect of serial stenosis on vascular resistance. Multiple single-center studies with coronary CTA and MPI have demonstrated the relatively poor ability of coronary CTA to predict ischemia on perfusion imaging with a modest PPV ~30%.41 Similarly, a normal myocardial perfusion scan is a relatively poor discriminator for the presence or absence of nonobstructive CAD.42 In addition, the extent of CAD can often be underestimated due to reduced heterogeneity of flow in patients with underlying CAD and concomitant endothelial dysfunction. Given the imperfect relationship between anatomic lesion severity and the degree of ischemia, a hybrid approach of radionuclide MPI and coronary CTA may allow for a more comprehensive characterization of CAD burden. However, both coronary CTA and MPI may not be indicated in all patients. A strategy of sequential imaging with initial MPI followed by coronary CTA (if MPI is not normal or severely abnormal) may be considered in subjects with an intermediate to high pretest likelihood. In contrast, an initial coronary CTA followed by MPI (unless the coronary CTA demonstrates normal arteries or critical CAD) may be a better strategy in subjects with low or low intermediate pretest likelihood of CAD. Others have proposed a coronary CTA along with stress MPI. An example of how this hybrid approach can provide useful clinical information is demonstrated in Figure 25-6.
A 42-year-old female with hypertension and family history of premature coronary atherosclerosis presented with chest pain. Exercise myocardial perfusion SPECT images demonstrated a small defect of moderate intensity involving the apical septum and true apex that is completely reversible. Coronary CT angiogram reveals a noncalcified plaque involving the proximal left anterior descending artery (LAD; black arrow in axial plane, white arrow on short axis of LAD) with a severe stenosis of >70%. Invasive coronary angiography confirmed severe mid-LAD stenosis (bottom left panel shows long-axis views and the right panel shows short-axis views of the mid-LAD lesion) that was stented successfully.
Several studies to date support the notion that both CAC score and coronary CTA offer incremental diagnostic and prognostic information to MPI. A few clinical scenarios wherein a hybrid approach of combined MPI along with coronary CTA may be helpful are: (1) to detect severe multivessel CAD in the setting of mild perfusion abnormalities when the clinical suspicion is high (balanced ischemia); (2) to diagnose microvascular dysfunction in subjects with abnormal MPI by excluding atherosclerosis; (3) to evaluate patients with structural abnormalities of the coronary arteries.43 Discordant findings on MPI and coronary CTA can result from microvascular dysfunction (abnormal blood flow without obstructive epicardial CAD, calcified and nonobstructive CAD with normal perfusion or obstructive CAD that is not flow-limiting (due to hemodynamic or collateral changes), and imaging artifacts. Therefore, combined MPI and CTA can provide better characterization of the extent and severity of underlying CAD and potential benefit from revascularization than does either technique alone.18 Indeed, one recent study showed that combining stress-only SPECT with coronary CTA in individuals presenting to the emergency room offers the added advantage of feasibility (no contraindications to SPECT), lower radiation dose when stress-only MPI was used, and higher prognostic value.44 However, the coronary CTA approach was less costly, and none of the individuals with a 0 calcium score had significant CAD or cardiac event during follow-up.
There is also emerging evidence that diagnostic performance of SPECT or PET MPI and coronary CTA is superior than SPECT/PET MPI or coronary CTA alone (Table 25-3).45–50 The EVINCI study, a multicenter study, included 292 symptomatic individuals with at least intermediate pretest likelihood of CAD, who underwent coronary CTA and at least one form of ischemia testing and were referred to invasive coronary angiography with an intention of evaluating FFR in intermediate lesions. These patients were followed up for 30 days and coronary revascularization was documented. Invasive coronary angiograms by QCA were considered obstructive with >50% stenosis in the left main or >70% stenosis in any of the other coronary arteries or 30% to 70% stenosis with an FFR ≤0.8. Majority of the individuals (70%) in the EVINCI study underwent SPECT MPI and the rest underwent PET MPI. Overall about 41% of the patients had normal hybrid imaging (MPI and coronary CTA normal) and 24% had a hybrid match (perfusion defect in the territory of a stenotic artery). As in prior single-center studies,51–54 rate of coronary revascularization was highest in the matched group (70%), intermediate in the mismatch group (36%), and least in the normal group (10%), p < 0.001. However, radiation dose with the hybrid imaging approach was high (PET/coronary CTA: 9.4 mSv and SPECT/coronary CTA: 18.5 mSv (range 6–31 mSv). Before advocating a combined imaging approach, larger studies with longer-term follow-up are necessary to determine the optimal strategy for hybrid imaging. Whether a combined imaging strategy improves patient outcomes by identification of patients who will benefit from revascularization, avoidance of invasive angiography, or improved adherence to optimal medical therapy is still being determined.
Table 25-3Diagnostic Accuracy of Integrated MPI and Coronary CTA: Vessel-Based Analysis in Identifying Obstructive CAD on Invasive Angiography ||Download (.pdf) Table 25-3 Diagnostic Accuracy of Integrated MPI and Coronary CTA: Vessel-Based Analysis in Identifying Obstructive CAD on Invasive Angiography
|First Author/Year ||N ||Gold Standard (Definition of Significant CAD) ||Sensitivity ||Specificity ||PPV ||NPV ||Hybrid Technique |
|Namdar (2005)58 ||25 ||Flow limiting coronary stenoses requiring revascularization (ICA + PET) ||90 ||98 ||82 ||99 ||13N-ammonia PET/4 slice CT |
|Rispler (2007)46 ||56 ||Flow limiting coronary stenoses (>50% stenosis on ICA and SPECT positive) ||96 ||95 ||77 ||99 ||99mTc SPECT/16 slice CT |
|Groves (2009)59 ||33 ||>50% stenosis on ICA ||88 ||100 ||97 ||99 ||82Rb PET/64 slice CT |
|Sato (2010)60 ||130 ||>50% stenosis on ICA ||94 ||92 ||85 ||97 ||99mTc SPECT/64 slice CTc |
|Kajander (2010)61 ||107 ||Flow limiting coronary stenoses (>50% stenosis on ICA + FFR) ||93 ||99 ||96 ||99 ||15O-water PET/64 slice CT |
|Danad (2013)62 ||120 ||Flow limiting coronary stenoses, CFR (>50% stenosis on ICA + FFR) ||72 ||89 ||69 ||90 ||15O-water PET/64 slice CT |
|Thomassen (2013)63 ||44 ||ICA, QCA, 50% stenoses ||88 ||97 ||85 ||97 ||15O-water PET/64 slice CT |
|Schaap (2013)a54 ||98 ||Flow limiting coronary stenoses (>50% stenosis on ICA + FFR) ||96 ||95 ||96 ||95 ||99mTc SPECT/64 slice CT |
|Dong (2014)64 ||78 ||ICA/CTA ≥50% with ischemic SPECT defect ||89 ||92 ||81 ||96 ||99mTc SPECT/ 16 slice CT |
|Wintherb (2015)65 ||138 ||Flow limiting coronary stenoses (>50% stenosis on ICA) ||67 ||86 ||57 ||90 ||99mTc SPECT/ Dual source CT |
|Liga (2016)57 ||252 ||Flow limiting coronary stenoses ([>50% stenosis on ICA] or [30–50% stenosis on ICA and FFR +] and perfusion defect) ||83 ||68 ||NA ||NA ||SPECT/PET/CTA |
Hybrid Cardiac CT and Radionuclide Imaging
Cardiac Inflammation and Infection
Hybrid imaging is uniquely suited to localize radiotracer uptake in hotspot radionuclide imaging and for molecular imaging (Fig. 25-7). As discussed in Chapter 24,18F-FDG imaging is emerging as a valuable technique to diagnose and manage sarcoidosis and prosthetic valve or cardiac device infection, and provides incremental value to diagnose infective endocarditis in prosthetic valves and intracardiac devices wherein echocardiography, cardiac CT, and cardiac magnetic resonance imaging (CMR) may be inconclusive.
Positron emission tomography (PET)–computed tomographic (CT) imaging of morphology and biology. In a model of regional adenoviral transfer of the VEGF (121) gene to myocardium of healthy pigs, PET–CT using multiple molecular-directed radiotracers was employed. Representative short-axis tomographic images are shown. On the left is a short-axis image of contrast-enhanced multislice CT showing the location of titanium clip markings. On the right is PET image showing significant accumulation of the reporter probe [18F]fluoro-hydroxymethylbutyl-guanine (FHBG). The middle image (overlay of PET and CT) shows that the FHBG accumulation colocalizes with clip markings in areas expressing the herpes simplex virus 1-sr39tk receptor gene. (Reproduced with permission from Wagner B, Anton M, Nekolla SG, et al. Noninvasive characterization of myocardial molecular interventions by integrated positron emission tomography and computed tomography. J Am Coll Cardiol. 2006;48(10):2107–2115.)
Complex Congenital Heart Disease
Hybrid imaging is well suited for imaging individuals with complex congenital heart disease.55,56 In addition to improved image quality, and attenuation correct, the CT portion of the PET or SPECT MPI helps distinguish prosthetic material-related perfusion defects from fibrosis.