The Use and Efficacy of FFR-CT: Real-World Multicenter Audit of Clinical Data With Cost Analysis.

BACKGROUND: Fractional flow reserve-computed tomography (FFR-CT) is endorsed by UK and U.S. chest pain guidelines, but its clinical effectiveness and cost benefit in real-world practice are unknown. OBJECTIVES: The purpose of this study was to audit the use of FFR-CT in clinical practice against England's National Institute for Health and Care Excellence guidance and assess its diagnostic accuracy and cost. METHODS: A multicenter audit was undertaken covering the 3 years when FFR-CT was centrally funded in England. For coronary computed tomographic angiograms (CCTAs) submitted for FFR-CT analysis, centers provided data on symptoms, CCTA and FFR-CT findings, and subsequent management. Audit standards included using FFR-CT only in patients with stable chest pain and equivocal stenosis (50%-69%). Diagnostic accuracy was evaluated against invasive FFR, when performed. Follow-up for nonfatal myocardial infarction and all-cause mortality was undertaken. The cost of an FFR-CT strategy was compared to alternative stress imaging pathways using cost analysis modeling. RESULTS: A total of 2,298 CCTAs from 12 centers underwent FFR-CT analysis. Stable chest pain was the main symptom in 77%, and 40% had equivocal stenosis. Positive and negative predictive values of FFR-CT were 49% and 76%, respectively. A total of 46 events (2%) occurred over a mean follow-up period of 17 months; FFR-CT (cutoff: 0.80) was not predictive. The FFR-CT strategy costs £2,102 per patient compared with an average of £1,411 for stress imaging. CONCLUSIONS: In clinical practice, the National Institute for Health and Care Excellence criteria for using FFR-CT were met in three-fourths of patients for symptoms and 40% for stenosis. FFR-CT had a low positive predictive value, making its use potentially more expensive than conventional stress imaging strategies.

Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis.

BACKGROUND: Older patients with severe aortic stenosis (AS) are increasingly identified as having cardiac amyloidosis (CA). It is unknown whether concomitant AS-CA has worse outcomes or results in futility of transcatheter aortic valve replacement (TAVR). OBJECTIVES: This study identified clinical characteristics and outcomes of AS-CA compared with lone AS. METHODS: Patients who were referred for TAVR at 3 international sites underwent blinded research core laboratory 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy (Perugini grade 0: negative; grades 1 to 3: increasingly positive) before intervention. Transthyretin-CA (ATTR) was diagnosed by DPD and absence of a clonal immunoglobulin, and light-chain CA (AL) was diagnosed via tissue biopsy. National registries captured all-cause mortality. RESULTS: A total of 407 patients (age 83.4 ± 6.5 years; 49.8% men) were recruited. DPD was positive in 48 patients (11.8%; grade 1: 3.9% [n = 16]; grade 2/3: 7.9% [n = 32]). AL was diagnosed in 1 patient with grade 1. Patients with grade 2/3 had worse functional capacity, biomarkers (N-terminal pro-brain natriuretic peptide and/or high-sensitivity troponin T), and biventricular remodeling. A clinical score (RAISE) that used left ventricular remodeling (hypertrophy/diastolic dysfunction), age, injury (high-sensitivity troponin T), systemic involvement, and electrical abnormalities (right bundle branch block/low voltages) was developed to predict the presence of AS-CA (area under the curve: 0.86; 95% confidence interval: 0.78 to 0.94; p < 0.001). Decisions by the heart team (DPD-blinded) resulted in TAVR (333 [81.6%]), surgical AVR (10 [2.5%]), or medical management (65 [15.9%]). After a median of 1.7 years, 23% of patients died. One-year mortality was worse in all patients with AS-CA (grade: 1 to 3) than those with lone AS (24.5% vs. 13.9%; p = 0.05). TAVR improved survival versus medical management; AS-CA survival post-TAVR did not differ from lone AS (p = 0.36). CONCLUSIONS: Concomitant pathology of AS-CA is common in older patients with AS and can be predicted clinically. AS-CA has worse clinical presentation and a trend toward worse prognosis, unless treated. Therefore, TAVR should not be withheld in AS-CA.

How variable are the volumetric measurements from gated perfusion SPECT when a one-day stress-rest protocol is used?

BACKGROUND: Using myocardial perfusion scintigraphy (MPS), an increase in left ventricular (LV) volumes or a decrease in ejection fraction (EF) from rest to stress may be clinically important. The variation in these measures between the low-dose stress acquisition and high-dose rest acquisition in a one-day stress-rest protocol has not been established. We assessed the reproducibility of gated volumetric indices between stress and rest and the normal variation in ungated TID ratio for a one-day stress-rest 99mTc-tetrofosmin protocol. METHODS: Two thousand and one hundred and fifty eight (2158) 99mTc-tetrofosmin MPS patient studies were analyzed retrospectively. Studies were excluded for incomplete data, significant technical difficulties, or (for gated analysis but not for analysis of TID ratio) if the LV EF was > 75%. An analysis of gated data was undertaken to establish the reproducibility of ventricular volumes and EF between stress and rest scans. Ungated volume data were analyzed to determine the confidence limits of TID ratio according to ventricular volume. RESULTS: Gated data were analyzed for 621 patients without inducible hypoperfusion. Mean EF at rest was slightly higher than after stress (62.4% ± 10.3% vs 61.2% ± 10.4%, P < 0.001), and the standard deviation of the difference was 5.2% (95% CI 4.9% to 5.5%). Ungated volumes were available for 992 non-ischaemic patients. The upper 95% CI for TID ratio was 1.23. This increased from 1.20 to 1.37 between the highest and lowest deciles of rest ungated volume. CONCLUSION: Using a one-day stress-rest 99mTc-tetrofosmin protocol, a fall in LV EF between rest and stress of > 11.6% or a TID ratio of > 1.23 is likely to be clinically reliable. The upper limit of normal for TID ratio needs to be increased for patients with small LV chamber volumes.

The rationale for the primacy of coronary CT angiography in the National Institute for Health and Care Excellence (NICE) guideline (CG95) for the investigation of chest pain of recent onset.

The National Institute for Health and Care Excellence (NICE) provides independent evidence-based guidance for England's National Health Service. Its 2010 guideline for the "assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin" (CG95) recommended a variety of first-line investigations in stable patients, depending on the pre-test probability (PTP) of obstructive coronary artery disease (CAD). Following a limited review, NICE produced an updated version of CG95 in 2016. Formal calculation of PTP is no longer advised. Coronary computed tomographic angiography (CCTA) is recommended as the first-line investigation for all patients with angina (or non-anginal pain but an abnormal electrocardiogram) and no prior CAD, with second-line functional imaging if the CCTA is equivocal. Notwithstanding some controversies regarding NICE's methodology, the updated version of CG95 can be justified on several levels. The focus on angina reflects evidence that patients with non-anginal pain have a similar prevalence of CAD to an asymptomatic population, and may not benefit from further investigation. The elimination of PTP is reasonable in patients required to have cardiac-sounding (anginal) symptoms. The ability of CCTA to identify non-obstructive atheroma, invisible to functional testing, might lead to improved medical treatment. Conversely the argument sometimes made for first-line functional testing, that ischemia-guided coronary revascularization leads to improved outcomes, has little hard evidence to support it. The performance of a separate functional test following equivocal CCTA may improve diagnostic specificity, and similar information is now obtainable from the CT study itself via computational flow dynamics.

Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease: the CvLPRIT trial.

BACKGROUND: The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction is uncertain. OBJECTIVES: CvLPRIT (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized study comparing complete revascularization at index admission with treatment of the infarct-related artery (IRA) only. METHODS: After they provided verbal assent and underwent coronary angiography, 296 patients in 7 U.K. centers were randomized through an interactive voice-response program to either in-hospital complete revascularization (n = 150) or IRA-only revascularization (n = 146). Complete revascularization was performed either at the time of P-PCI or before hospital discharge. Randomization was stratified by infarct location (anterior/nonanterior) and symptom onset (≤ 3 h or >3 h). The primary endpoint was a composite of all-cause death, recurrent myocardial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months. RESULTS: Patient groups were well matched for baseline clinical characteristics. The primary endpoint occurred in 10.0% of the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after complete revascularization (p = 0.055 at 30 days). Although there was no significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen. There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced nephropathy, or stroke between the groups. CONCLUSIONS: In patients presenting for P-PCI with multivessel disease, index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA. In such patients, inpatient total revascularization may be considered, but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival.

Advances in SPECT in evaluating coronary disease.

Myocardial perfusion scintigraphy is the longest established of the functional imaging investigations for patients with known or suspected coronary artery disease. This article describes recent technical and clinical advances that are ensuring that the technique remains relevant some 40 years after its first introduction.

Cardiac iodine-123 metaiodobenzylguanidine imaging predicts ventricular arrhythmia in heart failure patients receiving an implantable cardioverter-defibrillator for primary prevention.

OBJECTIVE: To assess the prognostic value of cardiac iodine-123 metaiodobenzylguanidine ((123)I-MIBG) scintigraphy to predict ventricular arrhythmias in patients with heart failure (HF) listed for implantable cardioverter-defibrillator (ICD) devices as primary prevention. DESIGN, SETTING AND PATIENTS: A prospective cohort study in 27 patients with HF referred for ICD implantation (alone or in combination with cardiac resynchronisation therapy) at a tertiary cardiac centre. METHODS: Cardiac (123)I-MIBG scintigraphy was performed with calculation of early and late heart-to-mediastinum (H:M) ratios, washout rate, and summed defect score from single photon emission computed tomography (SPECT) acquisition. Resting myocardial perfusion SPECT using (99m)Tc-tetrofosmin was also performed and a summed score calculated. Innervation-perfusion mismatch was evaluated by comparing SPECT scores. MAIN OUTCOME MEASURE: Ventricular arrhythmia requiring ICD therapy. RESULTS: At 16 months median follow-up, 10 (37%) patients experienced a significant arrhythmic event. Compared with patients who suffered no event, these individuals had lower early and late H:M ratio and higher (123)I-MIBG SPECT defect scores: 1.83 ± 0.43 versus 2.34 ± 0.33 (p<0.001); 1.54 ± 0.38 versus 1.96 ± 0.38 (p=0.005); 37.0 ± 9.4 versus 25.5 ± 7.7 (p=0.001). Mismatch scores were also higher: 18.5 ± 8.5 versus 8.4 ± 5.0 (p<0.01). Optimal thresholds for predicting arrhythmia were <1.94 for early H:M ratio (sensitivity 70%, specificity 88%); <1.54 for late H:M ratio (sensitivity 60%, specificity 88%); (123)I-MIBG SPECT defect score ≥31 (sensitivity 78%, specificity 77%). CONCLUSIONS: In HF patients without prior ventricular arrhythmia, (123)I-MIBG imaging strongly predicts future arrhythmic risk. This may inform the process of case selection for ICD therapy on an individual basis, although no single measurement provides sufficient reassurance to obviate device implantation if otherwise clinically indicated.

Prognostic value of a nine-minute treadmill test in patients undergoing myocardial perfusion scintigraphy.

Exercise capacity is an important predictor of risk in known or suspected coronary disease. A negative treadmill test to 9 minutes of the Bruce protocol is often used in the screening process for vocational licensing; myocardial perfusion scintigraphy is an alternative for those unable to exercise, with apparent incremental prognostic power above exercise testing alone. We compared exercise test and myocardial perfusion scintigraphic (MPS) findings and risk of hard cardiac events (median 4 years) in patients completing ≥ 9-minute treadmill exercise. Patients undergoing myocardial perfusion scintigraphy who completed a 9-minute Bruce protocol exercise were identified over a 2-year period. Follow-up was performed by telephone, with case-note review when necessary; this was 97% complete. Five hundred sixteen patients were identified (73% men, median age 53 year). One hundred eighty-one (35%) had known coronary disease. One hundred forty-nine (29%) had a "high-risk" exercise test result (limiting chest pain or ST-segment depression), and 69 (13%) had high-risk MPS findings (>10% myocardium ischemic or ejection fraction <40%). Of 367 patients with a reassuring exercise test result, 38 (10.4%) had high-risk MPS findings. Of 149 with a high-risk exercise test, 118 (79%) had reassuring MPS findings. At median follow-up of 49 months, there were 8 cardiac events (1.6%). Only 2 patients with high-risk exercise test results (1.4%) and 1 with high-risk MPS findings (1.5%) had an event. In conclusion, for patients able to manage a 9-minute Bruce protocol, presence/absence of symptoms or electrocardiographic changes is a poor predictor of MPS findings. Irrespective of test findings, however, subsequent cardiac risk is extremely low. Ability to complete a 9-minute Bruce protocol treadmill exercise may itself provide adequate prognostic reassurance for most purposes.

Are diabetic patients less likely to feel angina than nondiabetic controls for a given extent of myocardial ischaemia?

OBJECTIVES: It is widely believed that diabetic patients with coronary artery disease have a reduced ability to feel angina. We investigated whether the diabetic patients referred for myocardial perfusion scintigraphy (MPS) are less likely to experience chest pain in daily life or during treadmill exercise than nondiabetic controls with equivalent extents of inducible hypoperfusion. METHODS: One hundred and fifteen diabetic patients with ischaemia on single-photon emission computed tomography (SPECT) MPS were matched with 115 nondiabetic controls for age, sex, ethnic origin, method of stress used for MPS, and the extent of reversible hypoperfusion. The prevalence of chest pain from the history and during treadmill exercise (where applicable) was compared between diabetic and nondiabetic patients. RESULTS: Of the diabetic patients, 18 (16%) were diet-controlled, 56 (49%) were treated with oral hypoglycaemic medication, and 41 (36%) used insulin. Compared with matched controls, diabetic patients were just as likely to give a history of chest pain (79 vs. 76%, P=NS), or to develop chest pain on the treadmill (31 vs. 39%, P=NS). CONCLUSION: When carefully matched for clinical factors and the extent of ischaemia, diabetic patients referred for MPS are just as likely to experience chest pain as nondiabetic controls, whether in daily life or during treadmill exercise testing.

Does myocardial perfusion scintigraphy predict improvement in symptoms and exercise capacity following successful elective percutaneous coronary intervention?

BACKGROUND: Elective percutaneous coronary intervention (PCI) without inducible ischaemia may not be beneficial. We investigated the prevalence of inducible hypoperfusion using myocardial perfusion scintigraphy (MPS) in patients undergoing PCI, and its ability to predict functional outcome. METHODS AND RESULTS: One hundred and twenty-three patients listed for elective PCI underwent MPS, using treadmill exercise where possible. Seventy-seven patients (63%) described chest pain in daily life. Seventy-four of 103 (72%) exercise ECG tests were positive. Ninety-one (74%) had inducible hypoperfusion on MPS (extensive in 25; 20%). Interventionalists were blinded to the scintigraphic results, and PCI was performed as planned. Six months later, Seattle Angina Questionnaire physical limitation score had improved from 66 to 76 (P < 0.0001), and peak treadmill workload from 7.2 +/- 2.3 to 9.0 +/- 2.7 METS (P < 0.0001). Sex, limiting chest pain on baseline exercise testing, and MPS summed difference score (SDS) were independent predictors of improvement. Patients with both limiting chest pain and SDS > or = 7 demonstrated an increase of 3.3 +/- 1.8 METS, compared with approximately 1.5 METS for other subgroups (P < 0.05). CONCLUSIONS: Many patients undergoing elective PCI in a UK centre have little or no evidence of inducible hypoperfusion. The combination of limiting chest pain during exercise testing and significant inducible hypoperfusion on MPS predicts a large increase in exercise capacity after PCI.

Is stress-only imaging practical when a 1-day stress-rest 99mTc-tetrofosmin protocol is used?

OBJECTIVES: To investigate whether a significant number of normal 1-day stress-rest 99mTc-tetrofosmin myocardial perfusion scintigraphy (MPS) studies can be identified from the low-dose stress acquisition alone, and whether technical staff can find such studies reliably. METHODS: The supervising consultant and four technologists independently graded the stress acquisitions from 200 consecutive MPS studies using a five-point scale. Studies were classified as normal or abnormal according to the final clinical report based on the completed stress-rest protocol. RESULTS: Between 31 and 62 studies (16-31%) were classified as definitely normal from the stress acquisition alone, of which 0-4 (0-9%) proved abnormal on the final report. Of stress studies graded definitely normal by each technologist, the consultant disagreed in 13-34% of cases. Of 78 stress studies graded definitely normal by at least one technologist, 6% turned out to be abnormal and the consultant disagreed in 33%. When there was agreement between at least two technologists (57 studies), the rates fell to 4% and 21% respectively. CONCLUSIONS: Technologists could make the decision to avoid a resting study in up to 30% of patients following a normal low-dose stress acquisition. The supervising nuclear cardiologist would disagree in perhaps one in five cases, even when there was consensus between two or more technologists. These patients would suffer minor inconvenience by being recalled for a rest acquisition on a second day, but there would be important savings in time and radiation exposure for the majority.