The impact of diabetes on the relationship of coronary artery disease and outcome: a study using multimodality imaging.

BACKGROUND: Patients with prediabetes or diabetes are at increased risk of developing cardiovascular disease and adverse outcomes. First-line coronary computed tomography angiography (CTA) followed by selective use of positron emission tomography (PET) myocardial perfusion imaging is a feasible strategy to diagnose and risk-stratify patients with suspected coronary artery disease (CAD). The aim of the present study was to study whether diabetes changes the relationship of CAD and long-term outcome. METHODS: We retrospectively identified consecutive symptomatic patients who underwent coronary CTA for suspected CAD. In patients with suspected obstructive CAD on CTA, myocardial ischemia was evaluated by 15O-water PET myocardial perfusion imaging. The relationship of the phenotype of CAD and long-term outcome in patients with no diabetes, prediabetes, or type 2 diabetes was investigated. A composite endpoint included all-cause mortality, myocardial infarction (MI), and unstable angina pectoris (UAP). RESULTS: A total of 1743 patients were included: 1214 (70%) non-diabetic, 259 (15%) prediabetic, and 270 (16%) type 2 diabetic patients. During 6.43 years of median follow-up, 164 adverse events occurred (106 deaths, 41 MIs, 17 UAPs). The prevalence of normal coronary arteries on CTA was highest in the non-diabetic patients (39%). The prevalence of hemodynamically significant CAD (abnormal perfusion) increased from 14% in non-diabetic patients to 20% in prediabetic and 27% in diabetic patients. The event rate was lowest in patients with normal coronary arteries and highest in patients with concomitant type 2 diabetes and hemodynamically significant CAD (annual event rate 0.2% vs. 4.7%). However, neither prediabetes nor diabetes were independent predictors of the composite adverse outcome after adjustment for the clinical risk factors and imaging findings. CONCLUSIONS: Coronary CTA followed by selective downstream use of PET myocardial perfusion imaging predicts long-term outcome similarly in non-diabetic and diabetic patients.

Global and segmental absolute stress myocardial blood flow in prediction of cardiac events: [15O] water positron emission tomography study.

PURPOSE: We evaluated the value of reduced global and segmental absolute stress myocardial blood flow (sMBF) quantified by [15O] water positron emission tomography (PET) for predicting cardiac events in patients with suspected obstructive coronary artery disease (CAD). METHODS: Global and segmental sMBF during adenosine stress were retrospectively quantified in 530 symptomatic patients who underwent [15O] water PET for evaluation of coronary stenosis detected by coronary computed tomography angiography. RESULTS: Cardiovascular death, myocardial infarction, or unstable angina occurred in 28 (5.3%) patients at a 4-year follow-up. Reduced global sMBF was associated with events (area under the receiver operating characteristic curve 0.622, 95% confidence interval (95% CI) 0.538-0.707, p = 0.006). Reduced global sMBF (< 2.2 ml/g/min) was found in 22.8%, preserved global sMBF despite segmentally reduced sMBF in 35.3%, and normal sMBF in 41.9% of patients. Compared with normal sMBF, reduced global sMBF was associated with the highest risk of events (adjusted hazard ratio (HR) 6.970, 95% CI 2.271-21.396, p = 0.001), whereas segmentally reduced sMBF combined with preserved global MBF predicted an intermediate risk (adjusted HR 3.251, 95% CI 1.030-10.257, p = 0.044). The addition of global or segmental reduction of sMBF to clinical risk factors improved risk prediction (net reclassification index 0.498, 95% CI 0.118-0.879, p = 0.010, and 0.583, 95% CI 0.203-0.963, p = 0.002, respectively). CONCLUSION: In symptomatic patients evaluated for suspected obstructive CAD, reduced global sMBF by [15O] water PET identifies those at the highest risk of adverse cardiac events, whereas segmental reduction of sMBF with preserved global sMBF is associated with an intermediate event risk.

Lipid-Lowering Medication and Outcomes After Anatomical and Functional Imaging in Suspected Coronary Artery Disease.

BACKGROUND: Anatomical and functional imaging identify different phenotypes of coronary artery disease (CAD) that may have implications for lipid-lowering medication (LLM). OBJECTIVES: The aim of this study was to assess the associations between LLM and long-term outcomes after combined anatomical and functional imaging in patients with suspected obstructive CAD. METHODS: Consecutive patients (n = 1,973; 41% men; median age: 63 years) underwent coronary computed tomography angiography (CTA) because of suspected CAD. Patients in whom obstructive CAD was not ruled out by CTA underwent ischemia testing by positron emission tomography. Data on LLM purchases were collected until 2 years, and the combined endpoints of death, myocardial infarction, and unstable angina pectoris were assessed at a median of 6.7 years. RESULTS: After imaging, LLM was used by 24% of patients with no CAD, 51% of patients with nonobstructive CAD, 72% of patients with obstructive CAD on CTA without myocardial ischemia, and 91% of patients with myocardial ischemia. The use of LLM decreased during follow-up, with 77% of patients with myocardial ischemia using LLM for 2 years. The use of LLM was associated with a lower annual rate of adverse events in patients with myocardial ischemia (6.1% vs 2.8%; P = 0.032) or obstructive CAD without myocardial ischemia (2.9% vs 1.4%; P = 0.004) but not in patients with nonobstructive CAD (1.5% vs 1.4%; P = 0.89) or no CAD (0.3% vs 0.3%; P = 0.68). CONCLUSIONS: The CAD phenotype defined by anatomical and functional imaging guides the use of LLM. The presence of myocardial ischemia and anatomical obstructive coronary lesions were associated with a long-term outcome benefit from LLM.

Prognostic value of combined coronary CT angiography and myocardial perfusion imaging in women and men.

AIMS: Combined anatomical and functional imaging enables detection of non-obstructive and obstructive coronary artery disease (CAD) as well as myocardial ischaemia. We evaluated sex differences in disease profile and outcomes after combined computed tomography angiography (CTA) and positron emission tomography (PET) perfusion imaging in patients with suspected obstructive CAD. METHODS AND RESULTS: We retrospectively evaluated 1948 patients (59% women) referred for coronary CTA due to suspected CAD during the years 2008-2016. Patients with a suspected obstructive lesion on coronary CTA (n = 657) underwent 15O-water PET to assess stress myocardial blood flow (MBF). During a mean follow-up of 6.8 years, 182 adverse events (all-cause death, myocardial infarction, or unstable angina) occurred. Women had more often normal coronary arteries (42% vs. 22%, P < 0.001) and less often abnormal stress MBF (9% vs. 28%, P < 0.001) than men. The annual adverse event rate was lower in women vs. men (1.2% vs. 1.7%, P = 0.02). Both in women and men, coronary calcification, non-obstructive CAD, and abnormal stress MBF were independent predictors of events. Abnormal stress MBF was associated with 5.0- and 5.6-fold adverse event rates in women and men, respectively. There was no interaction between sex and coronary calcification, non-obstructive CAD, or abnormal stress MBF in terms of predicting adverse events. CONCLUSION: Among patients evaluated for chronic chest pain, women have a lower prevalence of ischaemic CAD and a lower rate of adverse events. Combined coronary CTA and PET myocardial perfusion imaging predict outcomes equally in women and men.

Extensive and balanced reduction of myocardial blood flow in patients with suspected obstructive coronary artery disease: 15O-water PET study.

BACKGROUND: Detection of obstructive coronary artery disease (CAD) by stress myocardial perfusion imaging (MPI) is conventionally based on relative differences in perfusion. This may lead to either underestimation of the extent of myocardial ischemia, or the ischemia might be completely missed in case of balanced perfusion reduction. Using absolute quantification of myocardial blood flow (MBF) by positron emission tomography (PET), we evaluated how common are extensive and balanced myocardial perfusion abnormalities in symptomatic patients with suspected obstructive CAD. METHODS AND RESULTS: Among 758 consecutive symptomatic patients undergone coronary computed tomography angiography (CTA), 286 patients subsequently underwent quantitative 15O-water adenosine-stress PET MPI to assess the hemodynamic significance of suspected obstructive stenosis. Out of these, 46 (16%) patients had reduced (≤2.3 ml/g/min) absolute stress MBF in all three standard coronary territories (LAD, LCX, RCA). Subsequently, relative stress MBF in each coronary territory was calculated, considering a territory with the highest absolute stress MBF as a reference region. Among the 46 patients, 72% had significant regional heterogeneity in myocardial perfusion (defined as having ≥1 territory with relative stress MBF <80%) while the remaining 28% (4.5% of the whole MPI cohort) showed balanced perfusion reduction (all relative MBF values ≥80%). CONCLUSIONS: Among symptomatic patients with suspected obstructive stenosis on coronary CTA, quantitative PET revealed that 16% of patients had reduced stress MBF involving all three coronary artery territories, of whom approximately one third showed balanced reduction. Thus, in 4.5% of the patients the perfusion abnormalities could have been missed by conventional relative MPI analysis.

Prognostic Value of Coronary CT Angiography With Selective PET Perfusion Imaging in Coronary Artery Disease.

OBJECTIVES: The purpose of this study was to evaluate the prognostic value of sequential hybrid imaging strategy in which positron emission tomography (PET) perfusion imaging is performed selectively in patients with suspected obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA). BACKGROUND: Coronary CTA is an accurate diagnostic test for excluding obstructive CAD. However, the positive predictive value is suboptimal. METHODS: We investigated 864 consecutive symptomatic patients with intermediate probability of CAD who adhered to the sequential imaging approach. PET myocardial perfusion imaging using 15O-labeled water during adenosine stress was performed when suspected obstructive stenosis was present on coronary CTA. The major adverse events (AEs) including all-cause mortality, myocardial infarction (MI), and unstable angina pectoris (UAP) were recorded. RESULTS: During a median follow-up of 3.6 years, 16 deaths, 10 MIs, and 5 UAPs occurred. Obstructive CAD was excluded by coronary CTA in 462 (53%) patients who had significantly lower annual AE rate than did patients with suspected obstructive stenosis on coronary CTA (0.4% vs. 1.5%; p = 0.003). The latter underwent PET study, on which 195 (49%) had normal and 207 had abnormal perfusion. The annual rate of AEs was 5 times higher in those with abnormal perfusion than with normal perfusion (2.5% vs. 0.5%; p = 0.004). Patients with normal perfusion had AE rate comparable to patients without obstructive CAD on coronary CTA (p = 0.77). CONCLUSIONS: In patients with suspected CAD obstructive disease can be excluded in 53% of patients by coronary CTA, and these patients have good outcome. About one-half (49%) of the remaining patients have normal perfusion and event rate comparable to patients without obstructive CAD on coronary CTA while patients with ischemia have clearly worse outcome. Sequential approach utilizing anatomical imaging by coronary CTA followed by selective functional perfusion imaging is a feasible strategy to diagnose and risk-stratify patients with suspected CAD.

Coronary computed tomography angiography derived risk score in predicting cardiac events.

BACKGROUND: We evaluated the prognostic value of an integrated atherosclerosis risk score combining the markers of coronary plaque burden, location and composition as assessed by computed tomography angiography (CTA). METHODS: 922 consecutive patients underwent CTA for suspected coronary artery disease (CAD). Patients without atherosclerosis (n = 261) and in whom quantitative CTA analysis was not feasible due to image quality, step-artefacts or technical factors related to image acquisition or data storage (n = 153) were excluded. Thus, final study group consisted of 508 patients aged 63 ± 9 years. Coronary plaque location, severity and composition for each coronary segment were identified using automated CTA quantification software and integrated in a single CTA score (0-42). Adverse events (AE) including death, myocardial infarction (MI) and unstable angina (UA) were obtained from the national healthcare statistics. RESULTS: There were a total of 20 (4%) AE during a median follow-up of 3.6 years (9 deaths, 5 MI and 6 UA). The CTA risk score was divided into tertiles: 0-6.7, 6.8-14.8 and > 14.8, respectively. All MI (n = 5) and most of the other AE occurred in the highest risk score tertile (3 vs. 3 vs. 14, p = 0.002). After correction for age and gender, the CTA risk score remained independently associated with AE. CONCLUSIONS: Comprehensive CTA risk score integrating the location, burden and composition of coronary atherosclerosis predicts future cardiac events in patients with suspected CAD.

Frequency and angiographic characteristics of coronary microvascular dysfunction in stable angina: a hybrid imaging study.

AIMS: Coronary microvascular dysfunction (CMD) can cause angina in the absence of obstructive coronary artery disease (CAD). We studied the frequency and angiographic characteristics of CMD in symptomatic patients with suspected stable CAD and identified CMD as diffusely abnormal coronary vasodilator capacity by positron emission tomography (PET) perfusion imaging. METHODS AND RESULTS: We recruited prospectively 189 patients with intermediate pre-test probability of CAD who underwent coronary computed tomography angiography and quantitative 15O-water PET perfusion imaging followed by invasive coronary angiography, and assessment of fractional flow reserve when feasible. Prevalence of obstructive epicardial CAD was 37%. Absolute myocardial blood flow was diffusely reduced (<2.4 mL/g/min) within the left ventricle during adenosine stress in 32 (17%) patients. In 15 (8%) patients, this was explained by three-vessel obstructive CAD, whereas the remaining 17 (9%) were diagnosed with CMD. Of these, 2 (1% of all patients) had no coronary atherosclerosis, 5 (3% of all patients) had non-obstructive atherosclerosis, and in 10 (5% of all patients) CMD co-existed with obstructive CAD. Atypical angina or non-anginal chest pain (53%) was the most common presentation. Older age and male sex were associated with CMD, but other risk factors of CAD were equally common in patients with or without CMD. CONCLUSION: Coronary microvascular dysfunction exists in 9% of symptomatic stable patients with suspected CAD. However, the prevalence of microvascular dysfunction without any coronary atherosclerosis is low (1%) in this population.

Incidence of persistent renal dysfunction after contrast enhanced coronary CT angiography in patients with suspected coronary artery disease.

Contrast-induced nephropathy (CIN) is a potentially serious complication of contrast agents used in computed tomography angiography (CTA). The aim of this study was to evaluate whether persistent renal dysfunction occurs in patients undergoing coronary CTA for suspected stable coronary artery disease (CAD). From a cohort of 957 patients undergone coronary CTA, we identified 402 patients with plasma creatinine levels collected before and within 6 months after CTA. According to the definition of CIN, patients with a ≥25 % increase in plasma creatinine after CTA were evaluated. The post-CTA measurements in 402 patients (195 men, age 62.9 ± 9.3 years) were performed at a median of 99 days after CTA. On average, there was no change in plasma creatinine level between the pre- and post-CTA measurements (75.8 ± 16.0 and 75.7 ± 16.4 µmol/L, respectively; P = 0.63) but both increases and decreases were commonly detected. Fourteen (3.5 %) patients had a ≥25 % increase in plasma creatinine levels after CTA. A more detailed evaluation of these patients revealed that in 4 patients the increase was explained by other morbidities, whereas in 9 patients the creatinine level returned to the previous levels at later follow-up (median time to normalization: 311 days). Only in 1 (0.2 %) remaining patient, there was a persistent increase in plasma creatinine level, possibly related to the iodine contrast agent exposure. Alterations in plasma creatinine concentration occur frequently. Persistent renal dysfunction attributable to iodine contrast agent exposure is rare in patients referred to coronary CTA for suspected CAD.