Georgios Benetos

Incremental Predictive Value of Carotid Inflammation in Acute Ischemic Stroke

Background and Purpose— Microwave Radiometry (MWR) allows in vivo noninvasive assessment of internal temperature of tissues. The aim of the present study was to evaluate in patients with ischemic stroke and bilateral carotid plaques (1) whether ipsilateral carotid arteries exhibit higher temperature differences (&Dgr;T), as assessed by MWR; (2) the predictive accuracy of MWR in symptomatic carotid artery identification. Methods— Consecutive patients with recent acute anterior circulation ischemic stroke because of large artery atherosclerosis were included in the study. Carotid arteries of all patients were evaluated by carotid ultrasound and MWR. Results— In total, 50 patients were included in the study. Culprit carotid arteries had higher &Dgr;T compared with nonculprit (0.93±0.58 versus 0.58±0.35°C; P<0.001). The addition of &Dgr;T to a risk prediction model based only on ultrasound plaque characteristics increased its predictive accuracy significantly (c-statistic: 0.691 versus 0.768; Pdif=0.05). Conclusions— Culprit carotid arteries show higher thermal heterogeneity compared with nonculprit carotid arteries in patients with acute ischemic stroke and bilateral carotid plaques. MWR has incremental value in culprit carotid artery discrimination.

Vulnerable plaque imaging: updates on new pathobiological mechanisms.

Early identification of vulnerable, rupture-prone atherosclerotic plaques with the optimal goal of cardiovascular event prevention is a field of vigorous research. Despite the advances in imaging modalities and the in vivo identification of many characteristics of vulnerability, few of these plaques actually rupture and even fewer lead to clinical events, questioning the predictive value of the above techniques in clinical practice. Factors causing the higher local vulnerability of the culprit plaque within a prothrombotic environment of widespread inflammation are generally unknown. Newly recognized local features, including microcalcifications and biomechanical factors, seem to contribute. In this review article, we target on new mechanisms, implicated in vulnerable plaque formation and rupture, analysing their potential clinical value.

Morphological and Functional Assessment of Carotid Plaques Have Similar Predictive Accuracy for Coronary Artery Disease

Background and Purpose— Microwave radiometry allows noninvasive in vivo measuring of internal temperature of tissues reflecting inflammation. In the present study, we evaluated the predictive accuracy of this method for the diagnosis of coronary artery disease (CAD). Methods— Consecutive patients (n=287) scheduled for coronary angiography were included in the study. In carotid arteries of both groups, the following measurements were performed: (1) intima-media thickness (IMTmax) and (2) temperature measurements by microwave radiometry (&Dgr;Tmax). C-statistic and net reclassification improvement were used to compare the prediction ability of the markers IMTmax and &Dgr;Tmax for the presence of CAD and multivessel CAD. Results— Of 287 patients, 239 had stenoses ≥50% (CAD group), and 48 did not have significant stenoses (NO-CAD group). &Dgr;Tmax was an independent predictor for the presence of CAD and multivessel CAD, showing similar predictive accuracy to intima-media thickness, as assessed by c-statistic and net reclassification improvement. Conclusions— Local inflammatory activation, as detected by microwave radiometry, has similar predictive accuracy to intima-media thickness for the presence and extent of CAD.

Catheter based inhibition of arterial calcification by bisphosphonates in an experimental atherosclerotic rabbit animal model.

BACKGROUND Vascular calcification is an active process, sharing common molecular mechanisms with bone formation. Bisphosphonates are components, which inhibit calcification. The aim of the present study was to evaluate the safety and effectiveness of local delivery of the bisphosphonate zoledronate on inhibition of calcium formation in the arterial wall in an experimental animal model. METHODS Sixteen New Zealand rabbits were placed on vitamin D enriched atherogenic diet for 3 weeks. Subsequently, all animals underwent angiography of abdominal aorta and common iliac arteries. A mixture containing 500 μg/l zoledronate was delivered on the vascular wall of the target iliac artery, using a dedicated balloon catheter. A placebo mixture was administered on the contralateral iliac artery of each animal, which was used as control. At 28 days all animals were sacrificed. Histologic sections of each common iliac artery were stained with hematoxylin-eosin and von Kossa. Computer-assisted histomorphometry was performed for the calcium content quantification of each section from the target and the control iliac artery. RESULTS In all animals the local delivery of zoledronate and placebo mixtures was successful and uncomplicated. The mean percentage of the calcium content of the media was higher in the control artery segments compared to the target (2.66 ± 0.73 versus 1.08 ± 0.62 % of the area of the media, p<0.01). CONCLUSIONS Inhibition of vascular calcification by local catheter-based delivery of bisphosphonate zolendronic acid is effective without evident short-term complications. These finding and its potential clinical implication remain to be confirmed in human studies.

Effects of Chios mastic gum on cholesterol and glucose levels of healthy volunteers: A prospective, randomized, placebo-controlled, pilot study (CHIOS-MASTIHA):

Background Chios mastic gum (CMG) possesses anti-oxidant, anti-inflammatory, anti-atheromatic, lipid- and glucose-lowering properties. We evaluated the effects of CMG on cholesterol and fasting plasma glucose (FPG) levels of healthy volunteers. Design A prospective, randomized, placebo-controlled, pilot study. Methods One hundred and seventy nine volunteers with total cholesterol levels >200 mg/dl were randomized to four groups. Finally, 156 volunteers completed the follow-up period and were analysed: (1) control group (C, n = 23), receiving placebo; (2) total mastic (TM, n = 72) receiving daily a total dose of 1 g of crude CMG (330 mg capsules, tid); (3) polymer-free mastic (PFM, n = 33), receiving daily a total dose of 1 g of polymer free mastic (330 mg caps, tid); and (4) powder mastic (PM, n = 28), receiving daily a total dose of 2 g of crude CMG. Results After eight weeks, the TM group reduced total cholesterol by 11.5 mg/dl (p < 0.05) and FPG by 4.5 mg/dl (p < 0.05) adjusted for age, gender, BMI and baseline characteristics. The effect was stronger in overweight and obese patients (BMI > 25), with an estimated mean reduction of total cholesterol by 13.5 mg/dl (p < 0.05) and FPG by 5.1 mg/dl (p < 0.05). Administration of PFM and PM resulted in no statistically significant alteration. No effect was observed on LDL, HDL, triglycerides, uric acid and CRP. No gastrointestinal, liver or renal adverse events were recorded. Conclusions CMG has a significant lowering effect on total cholesterol and glucose levels of healthy volunteers, with excellent tolerance and no detectable side effects, especially in overweight and obese individuals.

Inflamed human carotid plaques evaluated by PET/CT exhibit increased temperature: insights from an in vivo study

Aims To explore the relationship between temperature measurements derived by microwave radiometry (MWR) and carotid flurodeoxyglucose (FDG) uptake and assess their association with histological and immunohistochemistry findings in patients with high-grade carotid stenosis. Methods and results In 21 patients undergoing carotid endarterectomy, carotid inflammation was evaluated by both FDG positron emission/computed tomography (FDG-PET/CT) imaging and MWR measurements. Carotid inflammation was assessed by PET/CT as target-to-background ratio (TBR) by obtaining measurements in consecutive axial slices 2 cm below to 2 cm above the carotid bifurcation. Temperature difference (ΔT) by MWR was assigned as the maximum-minimum temperature measurements over the corresponding carotid segments. The extent of lipid core, calcification as well as CD68 and CD31 levels were also assessed. There was a significant correlation between ΔT values and FDG uptake (R = 0.40, P = 0.01), but no correlation between the degree of angiographic stenosis and ΔT values (R = -0.02, P = 0.91) or PET/CT measurements (R = -0.28, P = 0.86). Patients with plaques containing high lipid core extension or low calcification exhibited higher ΔT (P = 0.001 and P < 0.001, respectively) and FDG uptake values (P = 0.02 and P = 0.02, respectively). Patients with plaques containing increased CD68 expression exhibited higher ΔT and FDG uptake measurements. Conclusion Carotid plaque inflammation was evaluated by temperature measurements, which were correlated with FDG-PET/CT indices, confirmed by histopathology and immunohistochemistry findings. Structural changes did not predict inflammatory process. The implications of these findings in risk stratification and management of patients with carotid atherosclerosis and the precise algorithm for potential clinical utilization of MWR and PET/CT remain to be determined.

Outcomes of Same Day Pacemaker Implantation after TAVI

Transcatheter aortic valve implantation (TAVI) is often associated with conduction disturbances, followed by permanent pacemaker (PPM) implantation. Because of the potential reversibility of these conduction disorders, controversy exists regarding the right timing of PPM implantation. TAVI is routinely performed under dual‐antiplatelet and antithrombotic therapy, which poses an additional hemorrhagic risk on a same‐day procedure. The aim of the present study was to evaluate the safety and effectiveness of same‐day PPM implantation in patients undergoing TAVI.

Advances in anticoagulation management of patients undergoing cardioversion of nonvalvular atrial fibrillation

Atrial fibrillation (AF) is a major cause of stroke. The restoration of sinus rhythm through cardioversion, either chemical or electrical is a common practice. Interestingly, there is an incremental increase from the baseline risk for embolisation in the immediate post-cardioversion period, with most events occurring within 10 days from cardioversion. Especially patients with recent onset AF show the lowest rates of antithrombotic therapy, while having a high stroke risk. Despite the increased risk for embolisation, anticoagulation in patients undergoing cardioversion of atrial fibrillation is often inadequate. Moreover, since the implementation of non-vitamin K antagonists oral anticoagulants (DOACs) there are several therapeutic approaches for pericardioversion anticoagulant therapy and not all suits to all patients. In addition, the extensive use of transesophageal echocardiography provides an alternative strategy, especially useful for patients of high haemorrhagic risk. In this review article, we aim to provide an update on the anticoagulation strategies for patients undergoing cardioversion of non-valvular atrial fibrillation in the advent of the use of DOACs.

INHIBITION OF AORTIC VALVE CALCIFICATION IN AN EXPERIMENTAL MODEL OF AORTIC VALVE STENOSIS

Local delivery of bisphosphonates has been proven to inhibit calcification of the arterial wall in an experimental model of atherosclerosis. The aim of the present study was to evaluate the anticalcific action of bisphosphonates on the aortic valve in an experimental model of aortic stenosis.

Female gender is independently associated with increased carotid temperatures in patients with coronary artery disease

BACKGROUND Limited are the data regarding the sex differences in functional carotid artery characteristics. Microwave Radiometry (MWR) is a new noninvasive method, which measures in vivo instantly the internal temperatures of tissues, reflecting inflammation. The aim of the present study was to investigate whether in patients with coronary artery disease (CAD), gender related differences apply in carotid plaque functional characteristics, as assessed by MWR. METHODS Consecutive patients with significant CAD were included in the study. All patients underwent evaluation of both carotid arteries by 1) ultrasound and 2) MWR. During ultrasound common carotid IMT and plaque thickness were assessed according to Mannheim consensus. During MWR measurements, temperature difference (ΔT) was assigned as maximal temperature along the carotid artery minus minimum. ΔT ≥0.90°C was assigned as high ΔT. RESULTS In total 364 patients with significant CAD were included in the study. Of these 54 were female and 310 were male. Max plaque thickness and ccIMT were similar between males and females (2.38±1.16 vs. 2.46±1.12mm, p=0.63 and 0.944±0.172 vs. 0.942±0.169mm, p=0.96). Carotid arteries of females showed higher ΔT values (1.16±0.48 vs 0.87±0.45°C, p<0.001). Interestingly, females had more commonly high ΔT values bilaterally (35.2% vs 15.5%, p=0.001). In multivariate analysis, female sex was independently associated with bilateral high ΔT, when adjusted to potential covariates (OR=2.78, 95% CI=1.42-5.45, p=0.003). CONCLUSIONS In patients with CAD, sex specific differences apply in functional but not in structural carotid artery characteristics. Whether this discrepancy has prognostic significance, remains to be clarified in future studies.