Outcomes of leadless pacemaker implantation in patients with mechanical heart valves.

INTRODUCTION: Device infections constitute a major complication of transvenous pacemakers. Mechanical heart valves (MHV) increase the risk of infective endocarditis (IE) and pacemaker infection, requiring lifelong vitamin K-antagonists (VKA), which may affect patient management. Leadless pacemakers (LP) are associated with low infection rates, posing an attractive option in MHV patients requiring permanent pacing. This study describes outcomes following LP implantation in patients with MHV. METHODS: This is a multicenter, observational, retrospective study including consecutive patients implanted with an LP at 5 centers between June 2015 and January 2020. Procedural outcomes, antithrombotic management, complications, performance during follow-up and episodes of bacteremia and IE were compared between patients with and without an MHV (MHV and non-MHV groups). RESULTS: Four hundred fifty-nine patients were included (74 in the MHV group, 16.1%, and 385 in the non-MHV group, 83.9%). Procedural outcomes and acute electrical performance were comparable between groups. Vascular complications and cardiac perforation occurred in 2.7 versus 2.3% (p = 1) and 0% versus 0.8% (p = 1) in the MHV group and non-MHV group. One case of IE occurred in the MHV group and 2 in the non-MHV group. In MHV patients, uninterrupted VKA was used in 83.8%, whereas 16.2% were heparin-bridged. Vascular complication or tamponade occurred in 1 (8.3%) MHV heparin-bridged patient versus 1 (1.6%) MHV uninterrupted VKA patient (p = .3). CONCLUSION: LP implantation outcomes in MHV patients are comparable to the general LP population. Device-related infections are rare following LP implantation, including in patients with MHV. In the MHV group, periprocedural anticoagulation management was not associated with significantly different rates of tamponade or vascular complication.

Lithotripsy for calcified in-stent restenosis. The "rock strata peeling pattern": A novel fracture pattern detected by optical coherence tomography.

Calcified neoatherosclerosis represents a particularly challenging scenario in patients with in-stent restenosis (ISR), frequently associated with worse angiographic and optical coherence tomography (OCT) results compared with other patients with typical ISR. Intravascular lithotripsy (IVL) has emerged as a safe and effective technology to circumferentially modify calcium in heavily calcified coronary lesions. Preliminary data also suggest its usefulness in calcified neoatheroscerosis. This case report aims to describe a novel fracture pattern after IVL identified by OCT (the "rock strata peeling pattern") in patients presenting with ISR due to calcified neoatherosclerosis.

The double injection technique to improve visualization of severe coronary lesions with optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is a high-resolution imaging modality that provides a precise evaluation of coronary anatomy. However, the presence of severe coronary lesions can prevent the required adequate distal contrast flushing resultting in inadequate blood clearance and poor image quality or complete blood shadowing of the underlying vessel wall. OBJECTIVES: The aim of this prospective study was to evaluate the feasibility and safety of a novel "double injection technique" (DIT) to overcome the limitations of the conventional technique (CT) in patients with severely stenotic lesions. METHODS: Twenty-three patients with severe angiographic lesions were sequentially imaged before intervention with OCT with the CT and then with DIT. A total of 5125 OCT frames were carefully matched and analyzed by an independent central core lab. A semiquantitative image quality score was used to grade the number of quadrants (0-4) with vessel wall visualization. RESULTS: Optimal OCT visualization (Grades 3-4) significantly improved by the DIT (68% vs. 38% of frames, p < 0.001). The DIT also improved the mean score (3.1 ± 0.6 vs. 2.0 ± 0.8; p < 0.05; mean improvement of 1.1 ± 0.5 per patient). There were no complications associated with the DIT. CONCLUSION: The DIT significantly improved preintervention image quality of OCT in severe coronary lesions.

Severe coronary spasm in a COVID-19 patient.

Myocardial injury is frequently detected in coronavirus disease 2019 (COVID-19) patients. However, up to one-third of COVID-19 patients showing ST-segment elevation on the electrocardiogram have angiographically normal coronary arteries. We present a case of an acute coronary syndrome due to a coronary spasm in a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patient. This pathophysiological mechanism was clearly demonstrated by intracoronary imaging techniques (optical coherence tomography) and invasive vasospasm test.

Dimensional analysis of the upper airway in obstructive sleep apnoea syndrome patients treated with mandibular advancement device: A bi- and three-dimensional evaluation.

BACKGROUND: The efficiency of the mandibular advancement device (MAD) in patients with obstructive sleep apnoea syndrome (OSAS) has been demonstrated. Nevertheless, the behaviour of the upper airway once MAD is placed and titrated, and its correlation with the apnoea-hypopnoea index (AHI) is still under discussion. OBJECTIVES: To analyse the morphological changes of the upper airway through a bi- and three-dimensional study and correlate it with the polysomnographic variable, AHI. METHODS: Patients were recruited from two different hospitals for the treatment of OSAS with a custom-made MAD. A cone-beam computer tomography and a polysomnography were performed at baseline and once the MAD was titrated. RESULTS: A total of 41 patients completed the study. Treatment with MAD reduced the AHI from 22.5 ± 16.8 to 9.2 ± 11.6 (p ≤ .05). There was a significant increase of the total airway volume with MAD from 21.83 ± 7.05 cm3 to 24.19 ± 8.19 cm3 , at the expense of the oropharynx. Moreover, the correlation between the improvement of the AHI and the augmentation of the volume of the upper airway was not statistically significant. CONCLUSIONS: The oral device used in this prospective study increased the mean upper pharyngeal airway volume and significantly reduced the AHI. Future studies that measure the muscular tone are needed to completely understand the association between the AHI and the physiological and anatomical response of the upper airway.

Magnesium-Based Resorbable Scaffold Versus Permanent Metallic Sirolimus-Eluting Stent in Patients With ST-Segment Elevation Myocardial Infarction: The MAGSTEMI Randomized Clinical Trial.

BACKGROUND: The use of poly-l-lactide acid-based bioresorbable scaffolds is limited in daily clinical practice because of safety concerns and lack of physiological benefit. Magnesium-based bioresorbable scaffold (MgBRS) presents a short resorption period (<1 year) and have the potential of being thromboresistant and exhibiting early restoration of vasomotor function. To date, however, no randomized clinical trial has investigated the performance of MgBRS. Therefore, this study aimed to compare the in-stent/scaffold vasomotion between MgBRS and permanent metallic sirolimus-eluting stent (SES) at 12-month follow-up in ST-segment-elevation myocardial infarction patients. METHODS: This investigator-driven, multicenter, randomized, single-blind, controlled trial randomized ST-segment-elevation myocardial infarction patients 1:1 to SES or MgBRS at 11 academic centers. The primary end point was the rate of increase (≥3%) after nitroglycerin in mean lumen diameter of the in-stent/scaffold segment at 12 months with superiority of MgBRS over SES in the as-treated population. The main secondary end points included angiographic parameters of restenosis, device-oriented composite end point, their individual components, and device thrombosis rate. Besides, endothelial-dependent vasomotor response to acetylcholine (ie, endothelial function) was also assessed in a subgroup of patients (n=69). RESULTS: Between June 2017 and June 2018, 150 ST-segment-elevation myocardial infarction patients were randomized (MgBRS, n=74; SES, n=76). At 1 year, the primary end point was significantly higher in the MgBRS arm (56.5% versus 33.8%; P=0.010). Conversely, late lumen loss was significantly lower in the SES group (in-segment: 0.39±0.49mm versus 0.02±0.27mm, P<0.001; in-device: 0.61±0.55mm versus 0.06±0.21mm; P<0.001). The device-oriented composite end point was higher in the MgBRS arm driven by an increase in ischemia-driven target lesion revascularization rate (12[16.2%] versus 4[5.2%], P=0.030). Definite thrombosis rate was similar between groups (1[1.4%] in the MgBRS arm versus 2[2.6%] in the SES group; P=1.0). Endothelial function assessment at device segment evidenced a more pronounced vasoconstrictive response to maximal dose of acetylcholine in the MgBRS arm (-8.3±3.5% versus -2.4±1.3% in the SES group, P=0.003). CONCLUSIONS: When compared to SES, MgBRS demonstrated a higher capacity of vasomotor response to pharmacological agents (either endothelium-independent or endothelium-dependent) at 1 year. However, MgBRS was associated with a lower angiographic efficacy, a higher rate of target lesion revascularization, without thrombotic safety concerns. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03234348.

Prospective, randomized trial of bioresorbable scaffolds vs. everolimus-eluting stents in patients undergoing coronary stenting for myocardial infarction: the Intracoronary Scaffold Assessment a Randomized evaluation of Absorb in Myocardial Infarction (ISAR-Absorb MI) trial.

Aims: Bioresorbable scaffolds (BRS) provide short-term coronary artery scaffolding and drug delivery. Although prior trials showed a higher rate of device failure compared with conventional drug-eluting stents (DES), only a single trial investigated patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (MI). We aimed to compare outcomes with BRS vs. DES in patients undergoing PCI for MI. Methods and results: We did a prospective, randomized, multicentre, non-inferiority, clinical trial of everolimus-eluting BRS vs. durable polymer everolimus-eluting stents (EES) in patients with acute MI. Patients were eligible for enrolment if they presented with ST-elevation MI, or non-ST-elevation MI with thrombosis visual at angiography and were randomly allocated to treatment with BRS or EES in 2:1 proportion. Angiographic follow-up was scheduled at 6-8 months and clinical follow-up was done at 12 months. The primary endpoint was percentage diameter stenosis in-segment at follow-up. A total of 262 patients were enrolled and were allocated to BRS (n = 173) or EES (n = 89). Angiographic follow-up was available for 213 (81.3%) patients. Mean diameter stenosis was 24.6 ± 12.2% with BRS vs. 27.3 ± 11.7% with EES (mean difference -2.7%, upper limit of one-sided 97.5% confidence limit 0.7%, pre-specified margin of non-inferiority 5%, Pnon-inferiority <0.001). The rate of the device-oriented composite of cardiac death/target vessel MI/target lesion revascularization [BRS: 12 (7.0%) vs. EES: 6 (6.7%), hazard ratio (HR) 1.04, 95% confidence interval (CI) 0.39-2.78] and definite/probable stent thrombosis [3 (1.7%) vs. 2 (2.3%), HR 0.76, 95% CI 0.13-4.56] were comparable in both groups. Conclusion: In patients undergoing PCI for acute MI BRS were non-inferior to EES for percentage diameter stenosis at angiographic follow-up. Rates of clinical events were comparable between the treatment groups, although the study was not powered to detect differences in clinical outcomes. Clinical trial registration: The trial was registered at www.clinicaltrials.gov (NCT01942070).

Early restenosis of resorbable magnesium scaffolds: Optical coherence tomography findings.

Resorbable Magnesium Scaffolds (RMS) represent an interesting alternative to current drug-eluting stents. Current data from clinical trials seems to confirm good performance of these new devices with low rates of late device failure. Little is known about mechanisms leading to RMS failure. Herein, we present the first description of an early RMS in-scaffold restenosis. Optical coherence tomography (OCT) analysis at implantation detected acute non-severe malapposition and underexpansion as main promoters of RMS failure. OCT during in-scaffold restenosis intervention confirmed early severe neointimal proliferation and RMS late recoil and dismantling as the main mechanisms of device failure. We hypothesize that the fast resorption process of RMS may lead to an early loss of radial strength, that could favor late recoil, acquired underexpansion, device dismantling and might interact with distribution of sirolimus. This case also illustrates that OCT is pivotal to unravel both acute and acquired mechanisms related to RMS failure.

Optical Coherence Tomography Findings in Patients With Coronary Stent Thrombosis: A Report of the PRESTIGE Consortium (Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort).

BACKGROUND: Stent thrombosis (ST) is a serious complication following coronary stenting. Intravascular optical coherence tomography (OCT) may provide insights into mechanistic processes leading to ST. We performed a prospective, multicenter study to evaluate OCT findings in patients with ST. METHODS: Consecutive patients presenting with ST were prospectively enrolled in a registry by using a centralized telephone registration system. After angiographic confirmation of ST, OCT imaging of the culprit vessel was performed with frequency domain OCT. Clinical data were collected according to a standardized protocol. OCT acquisitions were analyzed at a core laboratory. Dominant and contributing findings were adjudicated by an imaging adjudication committee. RESULTS: Two hundred thirty-one patients presenting with ST underwent OCT imaging; 14 (6.1%) had image quality precluding further analysis. Of the remaining patients, 62 (28.6%) and 155 (71.4%) presented with early and late/very late ST, respectively. The underlying stent type was a new-generation drug-eluting stent in 50.3%. Mean reference vessel diameter was 2.9±0.6 mm and mean reference vessel area was 6.8±2.6 mm2. Stent underexpansion (stent expansion index <0.8) was observed in 44.4% of patients. The predicted average probability (95% confidence interval) that any frame had uncovered (or thrombus-covered) struts was 99.3% (96.1-99.9), 96.6% (92.4-98.5), 34.3% (15.0-60.7), and 9.6% (6.2-14.5) and malapposed struts was 21.8% (8.4-45.6), 8.5% (4.6-15.3), 6.7% (2.5-16.3), and 2.0% (1.2-3.3) for acute, subacute, late, and very late ST, respectively. The most common dominant finding adjudicated for acute ST was uncovered struts (66.7% of cases); for subacute ST, the most common dominant finding was uncovered struts (61.7%) and underexpansion (25.5%); for late ST, the most common dominant finding was uncovered struts (33.3%) and severe restenosis (19.1%); and for very late ST, the most common dominant finding was neoatherosclerosis (31.3%) and uncovered struts (20.2%). In patients presenting very late ST, uncovered stent struts were a common dominant finding in drug-eluting stents, and neoatherosclerosis was a common dominant finding in bare metal stents. CONCLUSIONS: In patients with ST, uncovered and malapposed struts were frequently observed with the incidence of both decreasing with longer time intervals between stent implantation and presentation. The most frequent dominant observation varied according to time intervals from index stenting: uncovered struts and underexpansion in acute/subacute ST and neoatherosclerosis and uncovered struts in late/very late ST.

Effectiveness of a mandibular advancement device in obstructive sleep apnea patients: a prospective clinical trial.

PURPOSE: This study aimed to determine the effectiveness of a mandibular advancement device in a sample of obstructive sleep apnea syndrome patients by the evaluation of respiratory and neurophysiologic parameters and clinical symptoms. Second, the influence of certain predictor factors related with the patient and the intraoral device, were considered in the final response with this treatment option. METHODS: Forty-one patients constituted the final sample. Outcomes were measured using polysomnography, Epworth sleepiness scale and an analogue visual snoring scale, before treatment and once the device was properly titrated. RESULTS: Mean apnea-hypopnea index decreased from 22.5 ± 16.8 to 9.1 ± 11.6 (p ≤ 0.05), influencing only gender and Fujita index as predictor factors. The oxygen saturation, arousal index, percentages of sleep stages and sleep efficiency significantly improved with the mandibular advancement device (MAD) placement. The snoring index improved in absolute terms in 6.1 units and the excessive daytime sleepiness was reduced from 12.2 ± 4.7 to 8.5 ± 3.8 (p ≤ 0.00). CONCLUSIONS: The successful treatment rate with the MAD was 65.8%. The placement and posterior regulation of the intraoral appliance efficiently reduced the apnea-hypopnea index, improved the sleep quality and the clinical symptomatology associated. Obstructive sleep apnea syndrome is a highly prevalent disease. and dentists should be aware of the benefits enhanced by this prosthetic device, considered the first treatment option by certain physicians.

Diagnostic accuracy of a hybrid approach of instantaneous wave-free ratio and fractional flow reserve using high-dose intracoronary adenosine to characterize intermediate coronary lesions: Results of the PALS (Practical Assessment of Lesion Severity) prospective study.

OBJECTIVES: We sought to investigate the diagnostic accuracy of instantaneous wave-free ratio (iFR) and high-dose intracoronary adenosine fractional flow reserve (IC-FFR) compared with classical intravenous adenosine fractional flow reserve (IV-FFR) to assess coronary stenosis severity. The usefulness of two hybrid strategies combining iFR and high-dose IC-FFR was also evaluated. BACKGROUND: Physiological assessment of intermediate coronary stenoses to guide revascularization is currently recommended. METHODS: Consecutive real-world patients with angiographically intermediate coronary stenosis (40-80% diameter stenosis) were prospectively included in the PALS (Practical Assessment of Lesion Severity) study. In every target lesion iFR, high-dose IC-FFR and IV-FFR were systematically measured to assess the accuracy of an hybrid sequential approach combining iFR and IC-FFR. RESULTS: A total of 106 patients with 121 intermediate coronary lesions were analyzed. Both, iFR and IC-FFR showed a significant correlation with IV-FFR (iFR: r = 0.60, 95%CI 0.48-0.70; IC-FFR: r = 0.88; 95%CI: 0.83-0.92). High-dose IC-FFR provided lower FFR values than IV-FFR (0.81 ± 0.08 vs. 0.82 ± 0.09, P = 0.25). Using a receiver-operating-characteristic curve an optimal iFR threshold of 0.91 for the screening test was identified. A sequential test strategy (initial iFR followed by IC-FFR only in lesions with iFR <0.91) yielded an excellent diagnostic accuracy (96.7%, 95%CI 96.7-99.1%) with a sensitivity, specificity, positive and negative predicted values of 100%, 94.7%, 91.8%, and 100%, respectively. A hybrid approach using the previously described iFR gray zone (0.85-0.94) also provided an excellent diagnostic accuracy (95%, 95%CI: 89.5-98.1%). CONCLUSIONS: In patients with intermediate coronary lesions a hybrid strategy by using a sequential approach of iFR and high-dose IC-FFR, provided a very good diagnostic performance to identify physiologically significant stenoses. © 2017 Wiley Periodicals, Inc.

A pooled analysis of the efficacy of fesoterodine for the treatment of overactive bladder, and the relationship between safety, co-morbidity and polypharmacy in patients aged 65 years or older.

Background: overactive bladder (OAB) is a common condition in older persons. Antimuscarinic treatment remains the mainstay of treatment of OAB but clinicians have been reluctant to prescribe this to older patients. This study examined efficacy and safety information from patients >65 in fesoterodine trials to reaffirm efficacy and to explore the relationships between treatment emergent adverse events (TEAEs), coexisting medication and co-morbidity. Methods: data from 10 double-blind, placebo-controlled studies were analysed. A logistic regression analysis, where TEAE incidence was predicted by treatment, prior antimuscarinic treatment, number of coexisting medications, number of concomitant diseases and all possible combinations of two-way interaction terms with treatment was conducted. Results: of 4,040 patients who participated in trials; fesoterodine treatment was associated with statistically significant reductions in all disease-related and patient-reported outcomes compared to placebo. There was a significant increase in the likelihood of reporting a TEAE in association with the number of coexistent medications (odds ratio (OR) = 1.028, 95% CI: 1.0143-1.044, P < 0.003). The OR of having a TEAE with increase in the number of concomitant diseases was 1.058 (95% CI: 1.044-1.072, P < 0.0001). Central nervous system (CNS) events were few. Discussion: fesoterodine treatment led to clinically meaningful improvements across all included patient reported outcomes. The number of concomitant conditions had the greatest influence on the likelihood of an adverse event being reported. CNS TEAE were not associated with fesoterodine dose and were low across all categories of concomitant disease and coexisting medication.

Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice.

Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a severe neuropsychiatric disorder that associates with prominent memory and behavioural deficits. Patients' antibodies react with the N-terminal domain of the GluN1 (previously known as NR1) subunit of NMDAR causing in cultured neurons a selective and reversible internalization of cell-surface receptors. These effects and the frequent response to immunotherapy have suggested an antibody-mediated pathogenesis, but to date there is no animal model showing that patients' antibodies cause memory and behavioural deficits. To develop such a model, C57BL6/J mice underwent placement of ventricular catheters connected to osmotic pumps that delivered a continuous infusion of patients' or control cerebrospinal fluid (flow rate 0.25 µl/h, 14 days). During and after the infusion period standardized tests were applied, including tasks to assess memory (novel object recognition in open field and V-maze paradigms), anhedonic behaviours (sucrose preference test), depressive-like behaviours (tail suspension, forced swimming tests), anxiety (black and white, elevated plus maze tests), aggressiveness (resident-intruder test), and locomotor activity (horizontal and vertical). Animals sacrificed at Days 5, 13, 18, 26 and 46 were examined for brain-bound antibodies and the antibody effects on total and synaptic NMDAR clusters and protein concentration using confocal microscopy and immunoblot analysis. These experiments showed that animals infused with patients' cerebrospinal fluid, but not control cerebrospinal fluid, developed progressive memory deficits, and anhedonic and depressive-like behaviours, without affecting other behavioural or locomotor tasks. Memory deficits gradually worsened until Day 18 (4 days after the infusion stopped) and all symptoms resolved over the next week. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies, predominantly in the hippocampus (maximal on Days 13-18), that after acid extraction and characterization with GluN1-expressing human embryonic kidney cells were confirmed to be against the NMDAR. Confocal microscopy and immunoblot analysis of the hippocampus showed progressive decrease of the density of total and synaptic NMDAR clusters and total NMDAR protein concentration (maximal on Day 18), without affecting the post-synaptic density protein 95 (PSD95) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. These effects occurred in parallel with memory and other behavioural deficits and gradually improved after Day 18, with reversibility of symptoms accompanied by a decrease of brain-bound antibodies and restoration of NMDAR levels. Overall, these findings establish a link between memory and behavioural deficits and antibody-mediated reduction of NMDAR, provide the biological basis by which removal of antibodies and antibody-producing cells improve neurological function, and offer a model for testing experimental therapies in this and similar disorders.

Frustrated expected reward induces differential transcriptional changes in the mouse brain.

Frustration represents a particular aspect of the addictive process that is related to loss of control when the expected reward is not obtained. We aim to study the consequences of frustrated expected reward on gene expression in the mouse brain. For this purpose, we used an operant model of frustration using palatable food as reward combined with microarrays. Transcriptomic profiles of frontal cortex, ventral striatum and hippocampus were analysed in five groups of mice: (1) positive control receiving palatable food and the cue light as conditioned stimulus; (2) frustrated group only receiving the cue light; (3) extinction learning group that did not receive palatable food nor the light; (4) negative control that never received the reinforcer nor the light during the whole experiment; and (5) yoked that received palatable food passively. Gene expression changes produced by frustration were revealed in the frontal cortex and ventral striatum, but not in the hippocampus. Most of the changes, such as the modification of the dopamine-DARPP-32 signalling pathway, were common in both areas and estimated to have neuronal origin. Extinction learning induced transcriptional changes only in the ventral striatum, with most genes showing down-regulation and without alteration in the dopamine-DARPP-32 signalling pathway. Active palatable food-seeking behaviour induced changes in gene expression in ventral striatum mainly affecting cell communication. In conclusion, frustration behaviour-induced changes in frontal cortex and ventral striatum mainly related to dopamine-DARPP-32 signalling that could play an important role in the loss of behavioural control during the addictive processes.

Relationships between serotonergic and cannabinoid system in depressive-like behavior: a PET study with [11C]-DASB.

Chronic stress represents a major environmental risk factor for mood disorders in vulnerable individuals. The neurobiological mechanisms underlying these disorders involve serotonergic and endocannabinoid systems. In this study, we have investigated the relationships between these two neurochemical systems in emotional control using genetic and imaging tools. CB1 cannabinoid receptor knockout mice (KO) and wild-type littermates (WT) were exposed to chronic restraint stress. Depressive-like symptoms (anhedonia and helplessness) were produced by chronic stress exposure in WT mice. CB1 KO mice already showed these depressive-like manifestations in non-stress conditions and the same phenotype was observed after chronic restraint stress. Chronic stress similarly impaired long-term memory in both genotypes. In addition, brain levels of serotonin transporter (5-HTT) were assessed using positron emission tomography. Decreased brain 5-HTT levels were revealed in CB1 KO mice under basal conditions, as well as in WT mice after chronic stress. Our results show that chronic restraint stress induced depressive-like behavioral alterations and brain changes in 5-HTT levels similarly to those revealed in CB1 KO mice in non-stressed conditions. These results underline the relevance of chronic environmental stress on serotonergic and endocannabinoid transmission for the development of depressive symptoms. Chronic restraint stress induces depressive-like behavior and reduced 5-HTT levels in WT mice similar to those revealed in non-stressed CB1-KO mice. Reduced 5-HTT in both genotypes increases synaptic 5-HT concentration. The 5-HT release is modulated through CB1 receptors and the absence of inhibitory CB1 receptor causes decreased inhibition of 5-HT release resulting in high synaptic 5-HT concentration that are not further enhanced by stress.

Spontaneous coronary artery dissection.

Spontaneous coronary artery dissection (SCAD) is a rare but challenging clinical entity of unknown etiology. From a pathophysiological standpoint, SCAD may occur in patients with a coronary intimal tear (presenting with the classic angiographic "flap" and multiple lumens), but also in patients without an intimal rupture (presenting as an intramural hematoma). Until now, available information on SCAD was largely based on multiple, small case-series studies but, recently, data from relatively large registries have cast a new light on this disease. Classically, SCAD was thought to present in young females without traditional atherosclerotic risk factors but recent reports suggest a broader clinical spectrum encompassing older patients with associated coronary artery disease. In this review, we concentrate on 3 main aspects of this unique disease: (1) the value of intracoronary diagnostic techniques (intravascular ultrasound and optical coherence tomography) to complement coronary angiography and to provide novel diagnostic insights on this elusive clinical condition; (2) the growing clinical evidence suggesting an association and potential causation between fibromuscular dysplasia and SCAD; and (3) the challenges of coronary revascularization in this adverse anatomic setting, together with recent data suggesting that a initial, conservative medical management may be preferable for the majority of patients with SCAD.