Early-onset versus late-onset preeclampsia and risk of coronary atherosclerosis later in life: a clinical follow-up study.

BACKGROUND: Younger women with previous preeclampsia have an increased risk of coronary atherosclerosis. It is unknown if this risk is associated with the time of onset of preeclampsia. OBJECTIVES: The aim of the study was to investigate if women with early-onset preeclampsia have a higher risk of coronary atherosclerosis compared to women with late-onset preeclampsia, independent of other perinatal risk factors. STUDY DESIGN: A total of 911 women with previous preeclampsia aged 35-55 years participated in a clinical follow-up study, including clinical examination, comprehensive questionnaires, and cardiac computed tomography scan 13 years (range 0-28) after index pregnancy. Early-onset preeclampsia versus late-onset preeclampsia was defined as gestational age at delivery < versus ≥ 34+0 gestational weeks, respectively. The primary outcome of the study was the presence of coronary atherosclerosis on the cardiac computed tomography. A logistic regression analysis was performed to investigate the association between time of onset of preeclampsia, perinatal risk factors and the primary outcome. RESULTS: Women with early-onset preeclampsia (N=139) were older (46.2±5.7 vs. 44.4±5.5 years, P<0.001), more likely to have hypertension (51.1% vs. 35.1%, P=<0.001), and had a higher body mass index (27.9±6.3 vs. 26.9±5.5 kg/m2, P=0.051) compared to women with late-onset preeclampsia (N=772) at follow-up. The prevalence of the primary outcome coronary atherosclerosis on the cardiac computed tomography was 28.8% vs. 22.2% (P=0.088) with an adjusted OR=1.74, 95% CI (1.01-3.01), P=0.045 after adjustment for maternal age at index pregnancy, pre-pregnancy body mass index, parity, diabetes in pregnancy, smoking in pregnancy, offspring birth weight and sex, and follow-up length. CONCLUSIONS: Women with early-onset preeclampsia had a slightly higher risk of coronary atherosclerosis compared to women with late-onset preeclampsia. However, based on the current evidence it does not seem indicated to limit screening, diagnostic and preventive measures for cardiovascular disease only to women with early-onset preeclampsia.

Normal values of myocardial blood flow measured with dynamic myocardial CT perfusion.

AIMS: Dynamic myocardial CT perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD.We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. METHODS AND RESULTS: A total of 82 healthy individuals (46 women) aged 45-78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 mL/min/g and 3.58 ± 1.14 mL/min/g respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress) and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant inter-segmental differences were found (P < 0.01), which was not related to age, sex or coronary dominance. CONCLUSION: Myocardial blood flow assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex or coronary dominance. Normal values of myocardial blood flow may be helpful in the clinical evaluation of suspected myocardial ischemia using DM-CTP.

Early Coronary Atherosclerosis in Women With Previous Preeclampsia.

BACKGROUND: Women with previous preeclampsia have an increased risk of coronary artery disease later in life. OBJECTIVES: This study aimed to determine the prevalence of coronary atherosclerosis in younger women with previous preeclampsia in comparison with women from the general population. METHODS: Women aged 40-55 years with previous preeclampsia were matched 1:1 on age and parity with women from the general population. Participants completed an extensive questionnaire, a clinical examination, and a coronary computed tomography angiography (CTA). The main study outcome was the prevalence of any coronary atherosclerosis on coronary CTA or a calcium score >0 in case of a nondiagnostic coronary CTA. RESULTS: A total of 1,417 women, with a mean age of 47 years, were included (708 women with previous preeclampsia and 709 control subjects from the general population). Women with previous preeclampsia were more likely to have hypertension (284 [40.1%] vs 162 [22.8%]; P < 0.001), dyslipidemia (338 [47.7%] vs 296 [41.7%]; P = 0.023), diabetes mellitus (24 [3.4%] vs 8 [1.1%]; P = 0.004), and high body mass index (27.3 ± 5.7 kg/m2 vs 25.0 ± 4.2 kg/m2; P < 0.001). Cardiac computed tomography was performed in all women. The prevalence of any coronary atherosclerosis was higher in the preeclampsia group (193 [27.4%] vs 141 [20.0%]; P = 0.001) with an OR: 1.41 (95% CI: 1.08-1.85; P = 0.012) after adjustment for age, dyslipidemia, diabetes mellitus, smoking, body mass index, menopause, and parity. CONCLUSIONS: Younger women with previous preeclampsia had a slightly higher prevalence of coronary atherosclerosis compared with age- and parity-matched women from the general population. Preeclampsia remained an independent risk factor after adjustment for traditional cardiovascular risk factors. (The CoPenHagen PREeClampsia and cardIOvascUlar diSease study [CPH-PRECIOUS]; NCT03949829).

Optimization of image sampling rate to lower the radiation dose of dynamic myocardial CT perfusion.

BACKGROUND: Dynamic myocardial CT perfusion (CTP) has emerged as a potential strategy to combine anatomical and functional evaluation in a single modality. However, this method results in a high radiation dose. METHODS: Dynamic CTP was performed in 56 patients with suspected or known ischemic heart disease of whom 48 had complete CT-data. Datasets with reduced sampling rate of 2- and 3 RR-intervals (2RR and 3RR) were constructed post hoc. Myocardial blood flow (MBF) estimates from the 2RR and 3RR datasets were compared with estimates based on the full dataset (1RR) using the two one-sided test of equivalence for paired samples. RESULTS: Significant equivalence was found for rest MBFLV (p â€‹< â€‹0.001), stress MBFLV (p â€‹< â€‹0.001) and for the CFRLV (p â€‹= â€‹0.005) when comparing 2RR blood flow estimates with the results based on the 1RR dataset. The 2RR reconstruction protocol led to an estimated reduction in radiation dose of 35.4 â€‹± â€‹3.8%. CONCLUSION: MBF can be quantitated with dynamic CTP using a sampling strategy of one volume for every second heartbeat. This strategy could lead to a significant reduction in radiation dose.

Non-invasive CT-derived fractional flow reserve and static rest and stress CT myocardial perfusion imaging for detection of haemodynamically significant coronary stenosis.

Computed tomography derived fractional flow reserve (FFRCT) and computed tomography stress myocardial perfusion imaging (CTP) are techniques to assess haemodynamic significance of coronary stenosis. To compare the diagnostic performance of FFRCT and static rest/stress CTP in detecting fractional flow reserve (FFR) defined haemodynamically-significant stenosis (FFR ≤ 0.8). Fifty-one patients (96 vessels) with suspected coronary artery disease from a single institution planned for elective invasive-angiography prospectively underwent research indicated 320-detector-CT-coronary-angiography (CTA) and adenosine-stress CTP and invasive FFR. Analyses were performed in separate core-laboratories for FFRCT and CTP blinded to FFR results. Myocardial perfusion was assessed visually and semi-quantitatively by transmural perfusion ratio (TPR). Invasive FFR ≤ 0.8 was present in 33% of vessels and 49% of patients. FFRCT, visual CTP and TPR analysis was feasible in 96%, 92% and 92% of patients respectively. Overall per-vessel sensitivity, specificity and diagnostic accuracy for FFRCT were 81%, 85%, 84%, for visual CTP were 50%, 89%, 75% and for TPR were 69%, 48%, 56% respectively. Receiver-operating-characteristics curve analysis demonstrated larger per vessel area-under-curve (AUC) for FFRCT (0.89) compared with visual CTP (0.70; p < 0.001), TPR (0.58; p < 0.001) and CTA (0.70; p = 0.0007); AUC for CTA + FFRCT (0.91) was higher than CTA + visual CTP (0.77, p = 0.008) and CTA + TPR (0.74, p < 0.001). Per-patient AUC for FFRCT (0.90) was higher than visual CTP (0.69; p = 0.0016), TPR (0.56; p < 0.0001) and CTA (0.68; p = 0.001). Based on this selected cohort of patients FFRCT is superior to visually and semi-quantitatively assessed static rest/stress CTP in detecting haemodynamically-significant coronary stenosis as determined on invasive FFR.

Relationship between patient presentation and morphology of coronary atherosclerosis by quantitative multidetector computed tomography.

AIMS: Quantitative computed tomography (QCT) allows assessment of morphological features of coronary atherosclerosis. We aimed to test the hypothesis that clinical patient presentation is associated with distinct morphological features of coronary atherosclerosis. METHODS AND RESULTS: A total of 1652 participants, representing a spectrum of clinical risk profiles [787 asymptomatic individuals from the general population, 468 patients with acute chest pain without acute coronary syndrome (ACS), and 397 patients with acute chest pain and ACS], underwent multidetector computed tomography. Of these, 274 asymptomatic individuals, 254 patients with acute chest pain without ACS, and 327 patients with acute chest pain and ACS underwent QCT to assess coronary plaque volumes and proportions of dense calcium (DC), fibrous, fibro fatty (FF), and necrotic core (NC) tissue. Furthermore, the presence of vulnerable plaques, defined by plaque volume and tissue composition, was examined. Coronary plaque volume increased significantly with worsening clinical risk profile [geometric mean (95% confidence interval): 148 (129-166) mm3, 257 (224-295) mm3, and 407 (363-457) mm3, respectively, P < 0.001]. Plaque composition differed significantly across cohorts, P < 0.0001. The proportion of DC decreased, whereas FF and NC increased with worsening clinical risk profile (mean proportions DC: 33%, 23%, 23%; FF: 50%, 61%, 57%; and NC: 17%, 17%, 20%, respectively). Significant differences in plaque composition persisted after multivariable adjustment for age, gender, body surface area, hypertension, statin use at baseline, diabetes, smoking, family history of ischaemic heart disease, total plaque volume, and tube voltage, P < 0.01. CONCLUSION: Coronary atherosclerotic plaque volume and composition are strongly associated to clinical presentation.

Reproducibility of quantitative coronary computed tomography angiography in asymptomatic individuals and patients with acute chest pain.

PURPOSE: Quantitative computed tomography (QCT) provides important prognostic information of coronary atherosclerosis. We investigated intraobserver and interobserver QCT reproducibility in asymptomatic individuals, patients with acute chest pain without acute coronary syndrome (ACS), and patients with acute chest pain and ACS. METHODS: Fifty patients from each cohort, scanned between 01/02/2010-14/11/2013 and matched according to age and gender, were retrospectively assessed for inclusion. Patients with no coronary artery disease, previous coronary artery bypass graft surgery, and poor image quality were excluded. Coronary atherosclerosis was measured semi-automatically by 2 readers. Reproducibility of minimal lumen area (MLA), minimal lumen diameter (MLD), area stenosis, diameter stenosis, vessel remodeling, plaque eccentricity, plaque burden, and plaque volumes was assessed using concordance correlation coefficient (CCC), Bland-Altman, coefficient of variation, and Cohen's kappa. RESULTS: A total of 84 patients (63 matched) were included. Intraobserver and interobserver reproducibility estimates were acceptable for MLA (CCC = 0.94 and CCC = 0.91, respectively), MLD (CCC = 0.92 and CCC = 0.86, respectively), plaque burden (CCC = 0.86 and CCC = 0.80, respectively), and plaque volume (CCC = 0.97 and CCC = 0.95, respectively). QCT detected area and diameter stenosis ≥50%, positive remodeling, and eccentric plaque with moderate-good intraobserver and interobserver reproducibility (kappa: 0.64-0.66, 0.69-0.76, 0.46-0.48, and 0.41-0.62, respectively). Reproducibility of plaque composition decreased with decreasing plaque density (intraobserver and interobserver CCC for dense calcium (>0.99; 0.98), fibrotic (0.96; 0.93), fibro-fatty (0.95; 0.91), and necrotic core tissue (0.89; 0.84). Reproducibility generally decreased with worsening clinical risk profile. CONCLUSIONS: Semi-automated QCT of coronary plaque morphology is reproducible, albeit with some decline in reproducibility with worsening patient risk profile.

Functional Information in Coronary Artery Disease: The Case of Computed Tomography Myocardial Perfusion.

PURPOSE OF REVIEW: To review methodological and logistical aspects of CT myocardial perfusion, current clinical evidence and possible future directions, with specific focus on use in patients with coronary artery disease (CAD). RECENT FINDINGS: CT myocardial perfusion imaging may be performed as an add-on to standard coronary CT angiography (CCTA), to identify regions of myocardial hypoperfusion, at rest and during adenosine stress. The principle of measurement is well-validated in animal experimental models, and CT myocardial perfusion imaging has a high degree of concordance with already clinically available perfusion imaging methods. Combining CCTA and CT myocardial perfusion imaging increases the diagnostic accuracy to identify patients with CAD associated with ischemia. In patients suspected of CAD, CCTA frequently detects coronary atherosclerotic lesions, in which revascularization could be clinically beneficial. CT myocardial perfusion imaging may be helpful to identify coronary lesions associated with myocardial ischemia, and thus potentially suitable for coronary intervention.

Prediction of clinical outcome by myocardial CT perfusion in patients with low-risk unstable angina pectoris.

The prognostic implications of myocardial computed tomography perfusion (CTP) analyses are unknown. In this sub-study to the CATCH-trial we evaluate the ability of adenosine stress CTP findings to predict mid-term major adverse cardiac events (MACE). In 240 patients with acute-onset chest pain, yet normal electrocardiograms and troponins, a clinically blinded adenosine stress CTP scan was performed in addition to conventional diagnostic evaluation. A reversible perfusion defect (PD) was found in 38 patients (16 %) and during a median follow-up of 19 months (range 12-22 months) 25 patients (10 %) suffered a MACE (cardiac death, non-fatal myocardial infarction and revascularizations). Accuracy for the prediction of MACE expressed as the area under curve (AUC) on receiver-operating characteristic curves was 0.88 (0.83-0.92) for visual assessment of a PD and 0.80 (0.73-0.85) for stress TPR (transmural perfusion ratio). After adjustment for the pretest probability of obstructive coronary artery disease, both detection of a PD and stress TPR were significantly associated with MACE with an adjusted hazard ratio of 39 (95 % confidence interval 11-134), p < 0.0001, for visual interpretation and 0.99 (0.98-0.99) for stress TPR, p < 0.0001. Patients with a PD volume covering >10 % of the LV myocardium had a worse prognosis compared to patients with a PD covering <10 % of the LV myocardium, p = 0.0002. The optimal cut-off value of the myocardial PD extent to predict MACE was 5.3 % of the left ventricle [sensitivity 84 % (64-96), specificity 95 % (91-97)]. Myocardial CT perfusion parameters predict mid-term clinical outcome in patients with recent acute-onset chest pain.

Endocardial-epicardial distribution of myocardial perfusion reserve assessed by multidetector computed tomography in symptomatic patients without significant coronary artery disease: insights from the CORE320 multicentre study.

AIM: Previous animal studies have demonstrated differences in perfusion and perfusion reserve between the subendocardium and subepicardium. 320-row computed tomography (CT) with sub-millimetre spatial resolution allows for the assessment of transmural differences in myocardial perfusion reserve (MPR) in humans. We aimed to test the hypothesis that MPR in all myocardial layers is determined by age, gender, and cardiovascular risk profile in patients with ischaemic symptoms or equivalent but without obstructive coronary artery disease (CAD). METHODS AND RESULTS: A total of 149 patients enrolled in the CORE320 study with symptoms or signs of myocardial ischaemia and absence of significant CAD by invasive coronary angiography were scanned with static rest and stress CT perfusion. Myocardial attenuation densities were assessed at rest and during adenosine stress, segmented into 3 myocardial layers and 13 segments. MPR was higher in the subepicardium compared with the subendocardium (124% interquartile range [45, 235] vs. 68% [22,102], P < 0.001). Moreover, MPR in the septum was lower than in the inferolateral and anterolateral segments of the myocardium (55% [19, 104] vs. 89% [37, 168] and 124% [54, 270], P < 0.001). By multivariate analysis, high body mass index was significantly associated with reduced MPR in all myocardial layers when adjusted for cardiovascular risk factors (P = 0.02). CONCLUSION: In symptomatic patients without significant coronary artery stenosis, distinct differences in endocardial-epicardial distribution of perfusion reserve may be demonstrated with static CT perfusion. Low MPR in all myocardial layers was observed specifically in obese patients.

Patterns of myocardial perfusion in humans evaluated with contrast-enhanced 320 multidetector computed tomography.

Left ventricular (LV) myocardial contrast enhancement can be recorded using 320 multi detector computed tomography (MDCT). We aimed to (1) assess patterns of regional myocardial perfusion at rest and compare them with NH(3) positron emission tomography (PET) (2) and to assess the effect of intravenous adenosine infusion on regional myocardial perfusion. To evaluate myocardial perfusion patterns at rest, we scanned 14 healthy subjects with PET and 14 age and gender matched subjects with 320 MDCT. To evaluate the effect of adenosine stress on relative perfusion patterns 14 subjects with near-normal epicardial coronary arteries were studied at rest and during adenosine stress. Relative perfusion was assessed as attenuation density (AD) in 16 segments of the LV, and each segment was divided into 3 layers: endo-, mid- and epi-cardial. During rest the relative AD by MDCT was lower in the lateral wall compared with the remainder of the LV (P < 0.002). A similar pattern was found by PET-imaging. LV endocardial AD was higher than mid- and epicardial AD (P < 0.05). At rest the endocardial/epicardial ratio in the septum was 0.99 compared with 1.23 in non-septal segments (P < 0.001). During adenosine infusion transmural AD increased due to significant increases in the mid- and epicardium and the endocardial/epicardial ratio decreased by 18% in non-septal segments (from 1.23 to 1.05 P < 0.001). Relative perfusion at rest is lower in the lateral wall of the LV with both PET and MDCT compared to the remainder of the myocardium. During adenosine stress endocardial/epicardial ratio decrease significantly.