Mohamed Ouhlous

In Vivo Characterization and Quantification of Atherosclerotic Carotid Plaque Components With Multidetector Computed Tomography and Histopathological Correlation

Objective—In a previous in vitro study we have demonstrated that atherosclerotic plaque components can be characterized with multidetector computed tomography (MDCT) based on differences in Hounsfield values (HV). Now we evaluated the use of MDCT in vivo to characterize and quantify atherosclerotic carotid plaque components compared with histology as reference standard. Methods and Results—Fifteen symptomatic patients with carotid stenosis (>70%) underwent MDCT angiography before carotid endarterectomy (CEA). From each CEA specimen 3 histological sections and corresponding MDCT images were selected. The HV of the major plaque components were assessed. The measured HV were: 657±416HU, 88±18HU, and 25±19HU for calcifications, fibrous tissue, and lipid core, respectively. The cut-off value to differentiate lipid core from fibrous tissue and fibrous tissue from calcifications was based on these measurements and set at 60 HU and 130 HU, respectively. Regression plots showed good correlations (R2>0.73) between MDCT and histology except for lipid core areas, which had a good correlation (R2=0.77) only in mildly calcified (0% to 10%) plaques. Conclusions—MDCT is able to quantify total plaque area, calcifications, and fibrous tissue in atherosclerotic carotid plaques in good correlation with histology. Lipid core can only be adequately quantified in mildly calcified plaques.

Cerebral Ischemia after Carotid Intervention

Purpose: To determine the incidence of symptomatic and asymptomatic cerebral ischemic lesions found on diffusion-weighted magnetic resonance imaging (DW-MRI) after carotid interventions. Methods: A prospective study was conducted to assess new cerebral ischemic lesions using DW-MRI in symptomatic patients with carotid artery disease undergoing protected carotid artery stenting (CAS) or carotid endarterectomy (CEA). DW-MRI was performed before and after the intervention in 44 patients (21 CAS and 23 CEA). Two experienced radiologists not involved in the carotid procedures or neurological assessment compared the postprocedural DW-MR images with those acquired before the intervention. Results: Three (6.8%) of the 44 patients suffered strokes: 1 major and 1 minor stroke after CEA and 1 minor stroke after CAS. DW-MRI showed 15 new hyperintense lesions in 2 (9%) of 23 CEA patients; 31 new hyperintense lesions were found in 9 (43%) of the 21 CAS patients. The majority of new lesions were located in the ipsilateral vascular territory; 2 CAS patients also showed 6 new hyperintense lesions in the cerebellum. The mean lesion load per patient was 2.52 cm3 (range 0.31–4.74) in the CEA group and 1.74 cm3 (0.03–9.72) in the CAS group (p=0.35). The volume of the individual lesions in CEA patients was 0.39 cm3 (range 0.01–2.16) compared to 0.52 cm3 (range 0.01–5.47) in the CAS group (p=0.23). Patients who were asymptomatic after the intervention had fewer lesions (p=0.03) and a smaller lesion load than symptomatic patients. Conclusions: Ischemic lesions were more frequently seen on DW-MRI after carotid stenting than after endarterectomy. The majority of the detected lesions did not cause neurological deficits.

Fractional Flow Reserve Computed from Noninvasive CT Angiography Data: Diagnostic Performance of an On-Site Clinician-operated Computational Fluid Dynamics Algorithm

PURPOSE To validate an on-site algorithm for computation of fractional flow reserve (FFR) from coronary computed tomographic (CT) angiography data against invasively measured FFR and to test its diagnostic performance as compared with that of coronary CT angiography. MATERIALS AND METHODS The institutional review board provided a waiver for this retrospective study. From coronary CT angiography data in 106 patients, FFR was computed at a local workstation by using a computational fluid dynamics algorithm. Invasive FFR measurement was performed in 189 vessels (80 of which had an FFR ≤ 0.80); these measurements were regarded as the reference standard. The diagnostic characteristics of coronary CT angiography-derived computational FFR, coronary CT angiography, and quantitative coronary angiography were evaluated against those of invasively measured FFR by using C statistics. Sensitivity and specificity were compared by using a two-sided McNemar test. RESULTS For computational FFR, sensitivity was 87.5% (95% confidence interval [CI]: 78.2%, 93.8%), specificity was 65.1% (95% CI: 55.4%, 74.0%), and accuracy was 74.6% (95% CI: 68.4%, 80.8%), as compared with the finding of lumen stenosis of 50% or greater at coronary CT angiography, for which sensitivity was 81.3% (95% CI: 71.0%, 89.1%), specificity was 37.6% (95% CI: 28.5%, 47.4%), and accuracy was 56.1% (95% CI: 49.0%, 63.2%). C statistics revealed a larger area under the receiver operating characteristic curve (AUC) for computational FFR (AUC, 0.83) than for coronary CT angiography (AUC, 0.64). For vessels with intermediate (25%-69%) stenosis, the sensitivity of computational FFR was 87.3% (95% CI: 76.5%, 94.3%) and the specificity was 59.3% (95% CI: 47.8%, 70.1%). CONCLUSION With use of a reduced-order algorithm, computation of the FFR from coronary CT angiography data can be performed locally, at a regular workstation. The diagnostic accuracy of coronary CT angiography-derived computational FFR for the detection of functionally important coronary artery disease (CAD) was good and was incremental to that of coronary CT angiography within a population with a high prevalence of CAD.

The natural and unnatural history of the Mustard procedure: long-term outcome up to 40 years

AIMS To describe long-term survival, clinical outcome and ventricular systolic function in a longitudinally followed cohort of patients after Mustard repair for transposition of the great arteries (TGA). There is serious concern about the long-term outcome after Mustard repair. METHODS AND RESULTS This longitudinal single-centre study consisted of 91 consecutive patients, who underwent Mustard repair before 1980, at age <15 years, and were evaluated in-hospital every 10 years. Survival status was obtained of 86 patients. Median follow-up was 35 (IQR 34-38) years. Cumulative survival was 84% after 10 years, 80% after 20 years, 77% after 30 years, and 68% after 39 years. Cumulative survival free of events (i.e. heart transplantation, arrhythmias, reintervention, and heart failure) was 19% after 39 years. Reinterventions were mainly required for baffle-related problems. Supraventricular and ventricular arrhythmias occurred in 28 and 6% of the patients, respectively. Pacemaker and/or ICD implantation was performed in 39%. Fifty survivors participated in the current in-hospital investigation including electrocardiography, 2D-echocardiography, cardiopulmonary-exercise testing, NT-proBNP measurement, Holter monitoring, and cardiac magnetic resonance. Right ventricular systolic function was impaired in all but one patient at last follow-up, and 14% developed heart failure in the last decade. NT-proBNP levels [median 31.6 (IQR 22.3-53.2) pmol/L] were elevated in 92% of the patients. Early postoperative arrhythmias were a predictor for late arrhythmias [HR 3.8 (95% CI 1.5-9.5)], and development of heart failure [HR 8.1 (95% CI 2.2-30.7)]. Also older age at operation was a predictor for heart failure [HR 1.26 (95% CI 1.0-1.6)]. CONCLUSION Long-term survival after Mustard repair is clearly diminished and morbidity is substantial. Early postoperative arrhythmias are a predictor for heart failure and late arrhythmias.

Unnatural history of tetralogy of fallot: Prospective follow-up of 40 years after surgical correction

Background— Prospective data on long-term survival and clinical outcome beyond 30 years after surgical correction of tetralogy of Fallot are nonexistent. Methods and Results— This longitudinal cohort study consists of the 144 patients with tetralogy of Fallot who underwent surgical repair at <15 years of age between 1968 and 1980 in our center. They are investigated every 10 years. Cumulative survival (data available for 136 patients) was 72% after 40 years. Late mortality was due to heart failure and ventricular fibrillation. Seventy-two of 80 eligible survivors (90%) participated in the third in-hospital investigation, consisting of ECG, Holter, echocardiography, cardiopulmonary exercise testing, N-terminal pro-brain natriuretic peptide measurement, cardiac magnetic resonance (including dobutamine stress testing), and the Short Form-36 questionnaire. Median follow-up was 36 years (range, 31–43 years). Cumulative event-free survival was 25% after 40 years. Subjective health status was comparable to that in the normal Dutch population. Although systolic right and left ventricular function declined, peak exercise capacity remained stable. There was no progression of aortic root dilation. A previous shunt operation, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality (hazard ratio, 2.9, 1.1, and 2.5, respectively). An increase in QRS duration and a deterioration of exercise tolerance and ventricular dysfunction did not predict mortality. Insertion of a transannular patch was a predictor for late arrhythmias (hazard ratio, 4.0; 95% confidence interval, 1.2–13.4). Conclusions— Although many patients needed a reoperation or developed arrhythmias, late mortality was low, and the clinical condition and subjective health status of most patients remained good. Previous shunt, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality. # CLINICAL PERSPECTIVE {#article-title-36}Background— Prospective data on long-term survival and clinical outcome beyond 30 years after surgical correction of tetralogy of Fallot are nonexistent. Methods and Results— This longitudinal cohort study consists of the 144 patients with tetralogy of Fallot who underwent surgical repair at <15 years of age between 1968 and 1980 in our center. They are investigated every 10 years. Cumulative survival (data available for 136 patients) was 72% after 40 years. Late mortality was due to heart failure and ventricular fibrillation. Seventy-two of 80 eligible survivors (90%) participated in the third in-hospital investigation, consisting of ECG, Holter, echocardiography, cardiopulmonary exercise testing, N-terminal pro-brain natriuretic peptide measurement, cardiac magnetic resonance (including dobutamine stress testing), and the Short Form-36 questionnaire. Median follow-up was 36 years (range, 31–43 years). Cumulative event-free survival was 25% after 40 years. Subjective health status was comparable to that in the normal Dutch population. Although systolic right and left ventricular function declined, peak exercise capacity remained stable. There was no progression of aortic root dilation. A previous shunt operation, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality (hazard ratio, 2.9, 1.1, and 2.5, respectively). An increase in QRS duration and a deterioration of exercise tolerance and ventricular dysfunction did not predict mortality. Insertion of a transannular patch was a predictor for late arrhythmias (hazard ratio, 4.0; 95% confidence interval, 1.2–13.4). Conclusions— Although many patients needed a reoperation or developed arrhythmias, late mortality was low, and the clinical condition and subjective health status of most patients remained good. Previous shunt, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality.

Calcium imaging and selective computed tomography angiography in comparison to functional testing for suspected coronary artery disease: the multicentre, randomized CRESCENT trial

AIMS To compare the effectiveness and safety of a cardiac computed tomography (CT) algorithm with functional testing in patients with symptoms suggestive of coronary artery disease (CAD). METHODS AND RESULTS Between April 2011 and July 2013, 350 patients with stable angina, referred to the outpatient clinic of four Dutch hospitals, were prospectively randomized between cardiac CT and functional testing (2 : 1 ratio). The tiered cardiac CT protocol included a calcium scan followed by CT angiography if the Agatston calcium score was between 1 and 400. Patients with test-specific contraindications were not excluded from study participation. By 1 year, fewer patients randomized to cardiac CT reported anginal complaints (P = 0.012). The cumulative radiation dose was slightly higher in the CT group (6.6 ± 8.7 vs. 6.1 ± 9.3 mSv; P < 0.0001). After 1.2 years, event-free survival was 96.7% for patients randomized to CT and 89.8% for patients randomized to functional testing (P = 0.011). After CT, the final diagnosis was established sooner (P < 0.0001), and additional downstream testing was required less frequently (25 vs. 53%, P < 0.0001), resulting in lower cumulative diagnostic costs (€369 vs. €440; P < 0.0001). CONCLUSION For patients with suspected stable CAD, a tiered cardiac CT protocol offers an effective and safe alternative to functional testing. Incorporating the calcium scan into the diagnostic workup was safe and lowered diagnostic expenses and radiation exposure.

Coronary CT Angiography for Suspected ACS in the Era of High-Sensitivity Troponins: Randomized Multicenter Study.

BACKGROUND It is uncertain whether a diagnostic strategy supplemented by early coronary computed tomography angiography (CCTA) is superior to contemporary standard optimal care (SOC) encompassing high-sensitivity troponin assays (hs-troponins) for patients suspected of acute coronary syndrome (ACS) in the emergency department (ED). OBJECTIVES This study assessed whether a diagnostic strategy supplemented by early CCTA improves clinical effectiveness compared with contemporary SOC. METHODS In a prospective, open-label, multicenter, randomized trial, we enrolled patients presenting with symptoms suggestive of an ACS at the ED of 5 community and 2 university hospitals in the Netherlands. Exclusion criteria included the need for urgent cardiac catheterization and history of ACS or coronary revascularization. The primary endpoint was the number of patients identified with significant coronary artery disease requiring revascularization within 30 days. RESULTS The study population consisted of 500 patients, of whom 236 (47%) were women (mean age 54 ± 10 years). There was no difference in the primary endpoint (22 [9%] patients underwent coronary revascularization within 30 days in the CCTA group and 17 [7%] in the SOC group [p = 0.40]). Discharge from the ED was not more frequent after CCTA (65% vs. 59%, p = 0.16), and length of stay was similar (6.3 h in both groups; p = 0.80). The CCTA group had lower direct medical costs (€337 vs. €511, p < 0.01) and less outpatient testing after the index ED visit (10 [4%] vs. 26 [10%], p < 0.01). There was no difference in incidence of undetected ACS. CONCLUSIONS CCTA, applied early in the work-up of suspected ACS, is safe and associated with less outpatient testing and lower costs. However, in the era of hs-troponins, CCTA does not identify more patients with significant CAD requiring coronary revascularization, shorten hospital stay, or allow for more direct discharge from the ED. (Better Evaluation of Acute Chest Pain with Computed Tomography Angiography [BEACON]; NCT01413282).

The unnatural history of an atrial septal defect: Longitudinal 35 year follow up after surgical closure at young age

Objective To describe the very long-term outcome after surgical closure of an atrial septal defect (ASD). Design Longitudinal cohort study of 135 consecutive patients who underwent surgical ASD repair at age <15 years between 1968 and 1980. The study protocol included ECG, echocardiography, exercise testing, N-terminal prohormone of brain natriuretic hormone, Holter monitoring and cardiac MRI. Main outcome measures Survival, major events (cardiac reinterventions, stroke, symptomatic arrhythmia or heart failure) and ventricular function. Results After 35 years (range 30–41), survival status was obtained in 131 of 135 patients (97%): five died (4%), including two sudden deaths in the last decade. Fourteen patients (16%) had symptomatic supraventricular tachyarrhythmias and six (6%) had a pacemaker implanted which was predicted by early postoperative arrhythmias. Two reoperations were performed. One ischaemic stroke occurred. Left ventricular (LV) and right ventricular (RV) ejection fractions (EF) were 58±7% and 51±6%, respectively. RVEF was diminished in 17 patients (31%) and in 11 (20%) the RV was dilated. Exercise capacity and quality of life were comparable to the normal population. No clear differences were found between ASD-II or sinus venosus type ASD. Conclusions Very long-term outcome after surgical ASD closure in childhood shows good survival and low morbidity. Early surgical closure prevents pulmonary hypertension and reduces the occurrence of supraventricular arrhythmias. Early postoperative arrhythmias are predictive for the need for pacemaker implantation during early follow-up, but the rate of late pacemaker implantation remains low. Although RVEF was unexpectedly found to be decreased in one-third of patients, the functional status remains excellent.

‘Prognostic implications of non-culprit plaques in acute coronary syndrome: non-invasive assessment with coronary CT angiography’

Aims Non-culprit plaques are responsible for a substantial number of future events in patients with acute coronary syndrome (ACS). In this study, we evaluated the prognostic implications of non-culprit plaques seen on coronary computed tomography angiography (CTA) in patients with ACS. Methods and results Coronary CTA was performed in 169 patients (mean 59 ± 11 years, 129 males) admitted with ACS. Data sets were assessed for the presence of obstructive non-culprit plaques (>50% luminal narrowing), segment involvement score, and quantitative measures of plaque burden, after censoring initial culprit plaques. Follow-up was performed for the occurrence of major adverse cardiovascular events (MACEs) unrelated to the initial culprit plaque; cardiac death, second ACS, or coronary revascularization after 90 days. After a median follow-up of 4.8 (IQR 2.6–6.6) years, MACE occurred in 36 (24%) patients: 6 cardiac deaths, 16 second ACS, and 14 coronary revascularizations. Dyslipidaemia (hazard ratio [HR] 3.1 [95% confidence interval 1.5–6.6]) and diabetes mellitus (HR 4.8 [2.3–10.3]) were univariable clinical predictors of MACE. Patients with remaining obstructive non-culprit plaques (HR 3.66 [1.52–8.80]) and higher plaque burden index (HR 1.22 [1.01–1.48]) had a more risk of MACE. In multivariate analysis, with diabetes, dyslipidaemia, and plaque burden index, obstructive non-culprit plaques (HR 3.76 [1.28–11.09]) remained an independent predictor of MACE. Conclusion Almost a quarter of the study population experienced a new event arising from a non-culprit plaque during a follow-up of almost 5 years. ACS patients with remaining obstructive non-culprit plaques or high plaque burden have an increased risk of future MACE.

Coronary CT angiography outperforms calcium imaging in the triage of acute coronary syndrome

BACKGROUND In this prospective study we determine the diagnostic value of coronary CT angiography (CTA) and calcium imaging in low to intermediate risk acute chest pain patients. METHODS One hundred and eleven consecutive patients (57 ± 11 years, 71 males) presenting to the emergency department with chest pain suggestive of acute coronary syndrome (ACS), but without indication for immediate catheter angiography, underwent both coronary CTA and calcium imaging without disclosure of the findings to the treating physicians. RESULTS ACS was diagnosed in 19 patients (17%). Coronary calcium was present in 71 patients (64%). Coronary CTA identified 74 (67%) patients with coronary plaque and 36 (32%) patients with obstructive (≥ 50%) plaque. The sensitivity and specificity of the calcium scan were: 89% and 41%. The sensitivity and specificity of coronary CTA were: 100% and 40% based on the presence of any plaque and 89% and 79% based on the presence of >50% stenosis. C-statistics of the GRACE risk score (0.77 [95% CI 0.66-0.89]) improved after addition of coronary CTA (0.93 [0.88-0.98], p<0.01), though not after addition of calcium scores (0.81 [0.71-0.91], p=0.52). Follow-up at 3 months revealed four late revascularizations (no deaths or myocardial infarctions), all of whom had obstructive CAD with calcium on CT at presentation. CONCLUSIONS Coronary CTA outperforms calcium imaging in the triage of patients suspected of developing ACS. Absence of plaque on coronary CTA allows safe discharge. Coronary CTA has incremental value to clinical risk scores and has the potential to reduce unnecessary hospital admissions.