Search

A European guideline on craniofacial microsomia was developed within the European Reference Network for rare and/or complex craniofacial anomalies and ear, nose, and throat disorders and published in 2020. The guideline provides an overview of optimal care provisions for patients with craniofacial microsomia and recommendations for the improvement of care. This document seeks to provide a tailored overview of this guideline for patients and their families.

Aims To compare cardiac magnetic resonance (CMR) measurement of T1 reactivity (DT1) with [ 15O]H 2O positron emission tomography (PET) measurements of quantitative myocardial perfusion. ................................................................................................................................................................................................... Methods Forty-three patients with suspected obstructed coronary artery disease underwent [ 15O]H 2O PET and CMR at and results 1.5-T, including rest and adenosine stress T1 mapping (ShMOLLI) and late gadolinium enhancement to rule out presence of scar tissue. DT1 was determined for the three main vascular territories and compared with [ 15O]H 2O PET-derived regional stress myocardial blood flow (MBF) and myocardial flow reserve (MFR). DT1 showed a significant but poor correlation with stress MBF (R 2 = 0.04, P = 0.03) and MFR (R 2 = 0.07, P = 0.004). Vascular territories with impaired stress MBF (i.e. 15O]H 2O PET measurements of absolute myocardial perfusion. Stress T1 and DT1 are lower in vascular territories with reduced stress MBF but have poor accuracy for detecting impaired myocardial perfusion.

Objectives: This study aimed to investigate the performance of computed tomography derived fractional flow reserve based interactive planner (FFRCT planner) to predict the physiological benefits of percutaneous coronary intervention (PCI) as defined by invasive post-PCI FFR. Background: Advances in FFRCT technology have enabled the simulation of hyperemic pressure changes after virtual removal of stenoses. Methods: In 56 patients (63 vessels) invasive FFR measurements before and after PCI were obtained and FFRCT was calculated using pre-PCI coronary CT angiography. Subsequently, FFRCT and invasive coronary angiography models were aligned allowing virtual removal of coronary stenoses on pre-PCI FFRCT models in the same locations as PCI was performed. Relationships between invasive FFR and FFRCT, between post-PCI FFR and FFRCT planner, and between delta FFR and delta FFRCT were evaluated. Results: Pre PCI, invasive FFR was 0.65 ± 0.12 and FFRCT was 0.64 ± 0.13 (p =.34) with a mean difference of 0.015 (95% CI: −0.23–0.26). Post-PCI invasive FFR was 0.89 ± 0.07 and FFRCT planner was 0.85 ± 0.07 (p CT were 0.23 ± 0.12 and 0.21 ± 0.12 (p =.09) with a mean difference of 0.025 (95% CI: −0.20–0.25). Significant correlations were found between pre-PCI FFR and FFRCT (r = 0.53, p CT planner (r = 0.41, p =.001), and between delta FFR and delta FFRCT (r = 0.57, p CT planner tool demonstrated significant albeit modest agreement with post-PCI FFR and change in FFR values after PCI. The FFRCT planner tool may hold promise for PCI procedural planning; however, improvement in technology is warranted before clinical application.

To evaluate the effect of percutaneous coronary intervention (PCI) of coronary chronic total occlusions (CTOs) on left ventricular (LV) strain assessed using cardiac magnetic resonance (CMR) tissue tracking. In 150 patients with a CTO, longitudinal (LS), radial (RS) and circumferential shortening (CS) were determined using CMR tissue tracking before and 3 months after successful PCI. In patients with impaired LV strain at baseline, global LS (10.9 ± 2.4% vs 11.6 ± 2.8%; P = 0.006), CS (11.3 ± 2.9% vs 12.0 ± 3.5%; P = 0.002) and RS (15.8 ± 4.9% vs 17.4 ± 6.6%; P = 0.001) improved after revascularization of the CTO, albeit to a small, clinically irrelevant, extent. Strain improvement was inversely related to the extent of scar, even after correcting for baseline strain (B = − 0.05; P = 0.008 for GLS, B = − 0.06; P = 0.016 for GCS, B = − 0.13; P = 0.017 for GRS). In the vascular territory of the CTO, dysfunctional segments showed minor improvement in both CS (10.8 [6.9 to 13.3] % vs 11.9 [8.1 to 15.0] %; P P

Objectives: This study evaluated myocardial viability as well as global and regional functional recovery after successful chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) using sequential quantitative cardiac magnetic resonance (CMR) imaging. Background: The patient benefits of CTO PCI are being questioned. Methods: In a single high-volume CTO PCI center patients were prospectively scheduled for CMR at baseline and 3 months after successful CTO PCI between 2013 and 2018. Segmental wall thickening (SWT) and percentage late gadolinium enhancement (LGE) were quantitatively measured per segment. Viability was defined as dysfunctional myocardium (50%, N = 26 [4%], −0.08 ± 1.09 mm, p < 0.01). Patients with ≥2 CTO segments viability showed more SWT increase in the CTO territory compared to patients with 0–1 segment viability (0.49 ± 0.93 vs. 0.12 ± 0.98 mm, p = 0.03). Conclusions: Detection of dysfunctional myocardial segments without extensive scar (≤50% LGE) as a marker for viability on CMR aids in identifying patients with significant regional functional recovery after CTO PCI.

Aims Myocardial ischaemic burden (IB) is used for the risk stratification of patients with coronary artery disease (CAD). This study sought to define a prognostic threshold for quantitative [15O]H2O positron emission tomography (PET)-derived IB. Methods and results A total of 623 patients with suspected or known CAD who underwent [15O]H2O PET perfusion imaging were included. The endpoint was a composite of death and non-fatal myocardial infarction (MI). A hyperaemic myocardial blood flow (hMBF) and myocardial flow reserve (MFR)-derived IB were determined. During a median follow-up time of 6.7 years, 62 patients experienced an endpoint. A hMBF IB of 24% and MFR IB of 28% were identified as prognostic thresholds. Patients with a high hMBF or MFR IB (above threshold) had worse outcome compared to patients with a low hMBF IB [annualized event rates (AER): 2.8% vs. 0.6%, P Conclusion A hMBF IB ≥24% was a stronger predictor of adverse outcome than an MFR IB ≥28%. Nevertheless, classifying patients according to concordance of IB result allowed for the identification of low- and high-risk patients.

Objectives: The authors sought to evaluate the impact of ischemic burden reduction after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on long-term prognosis and cardiac symptom relief. Background: The clinical benefit of CTO PCI is questioned. Methods: In a high-volume CTO PCI center, 212 patients prospectively underwent quantitative [ 15O]H 2O positron emission tomography perfusion imaging before and three months after successful CTO PCI between 2013-2019. Perfusion defects (PD) (in segments) and hyperemic myocardial blood flow (hMBF) (in ml · min −1 · g −1) allocated to CTO areas were related to prognostic outcomes using unadjusted (Kaplan-Meier curves, log-rank test) and risk-adjusted (multivariable Cox regression) analyses. The prognostic endpoint was a composite of all-cause death and nonfatal myocardial infarction. Results: After a median [interquartile range] of 2.8 years [1.8 to 4.3 years], event-free survival was superior in patients with ≥3 versus −1 · g −1) versus below the population median (p < 0.01; risk-adjusted p < 0.01; HR: 0.16 [95% CI: 0.05 to 0.54]) after CTO PCI. Furthermore, event-free survival was superior in patients without versus any residual PD (p < 0.01; risk-adjusted p = 0.02; HR: 0.22 [95% CI: 0.06 to 0.76]) or with a residual hMBF level >2.3 versus ≤2.3 ml · min −1 · g −1 (p < 0.01; risk-adjusted p = 0.03; HR: 0.25 [95% CI: 0.07 to 0.91]) at follow-up positron emission tomography. Patients with residual hMBF >2.3 ml · min −1 · g −1 were more frequently free of angina and dyspnea on exertion at long-term follow-up (p = 0.04). Conclusions: Patients with extensive ischemic burden reduction and no residual ischemia after CTO PCI had lower rates of all-cause death and nonfatal myocardial infarction. Long-term cardiac symptom relief was associated with normalization of hMBF levels after CTO PCI.

Background: This study aimed to investigate the diagnostic value of comprehensive on-site coronary computed tomography angiography (CCTA) using stenosis and plaque measures and subtended myocardial mass (V sub) for fractional flow reserve (FFR) defined hemodynamically obstructive coronary artery disease (CAD). Additionally, the incremental diagnostic value of off-site CT-derived FFR (FFR CT) was assessed. Methods: Prospectively enrolled patients underwent CCTA followed by invasive FFR interrogation of all major coronary arteries. Vessels with ≥30% stenosis were included for analysis. On-site CCTA assessment included qualitative and quantitative stenosis (visual grading and minimal lumen area, MLA) and plaque measures (characteristics and volumes), and V sub. Diagnostic value of comprehensive on-site CCTA assessment was tested by comparing area under the curves (AUC). In vessels with available FFR CT, the incremental value of off-site FFR CT was tested. Results: In 236 vessels (132 patients), MLA, positive remodeling, non-calcified plaque volume, and V sub were independent on-site CCTA predictors for hemodynamically obstructive CAD (p < 0.05 for all). V sub/MLA 2 outperformed all these on-site CCTA parameters (AUC = 0.85) and V sub was incremental to all other CCTA predictors (p = 0.02). In subgroup analysis (n = 194 vessels), diagnostic performance of FFR CT and V sub/MLA 2 was similar (AUC 0.89 and 0.85 respectively, p = 0.25). Furthermore, diagnostic performance significantly albeit minimally increased when FFR CT was added to on-site CCTA assessment (ΔAUC = 0.03, p = 0.02). Conclusions: In comprehensive on-site CCTA assessment, V sub/MLA2 demonstrated greatest diagnostic value for hemodynamically obstructive CAD and V sub was incremental to all evaluated CCTA indices. Additionally, adding FFR CT only minimally increased diagnostic performance, demonstrating that on-site CCTA assessment is a reasonable alternative to FFR CT. Several novel indices have been proposed to increase the diagnostic performance of coronary computed tomography angiography (CCTA). The diagnostic value of comprehensive on-site CCTA assessment using qualitative and quantitative stenosis and plaque measures and subtended myocardial mass (V sub) for fractional flow reserve (FFR) defined hemodynamically obstructive CAD was assessed in 236 vessels with ≥30% stenosis (132 patients). V sub/MLA 2 demonstrated greatest diagnostic value and V sub was incremental to all evaluated CCTA indices. The addition of off-site CT-derived FFR (FFR CT, in 192 vessels) only minimally increased diagnostic performance, demonstrating that on-site CCTA assessment is a reasonable alternative to off-site assessment using FFR CT.

Pulmonary hypertension is common in heart failure with preserved ejection fraction (HFpEF). Here, we tested the hypothesis that comorbidities [diabetes mellitus (DM, streptozotocin), hypercholesterolemia (HC, high-fat diet) and chronic kidney disease (CKD, renal microembolization)] directly impair pulmonary vasomotor control in a DM + HC + CKD swine model. 6 months after induction of DM + HC + CKD, pulmonary arterial pressure was similar in chronically instrumented female DM + HC + CKD (n = 19) and Healthy swine (n = 18). However, cardiac output was lower both at rest and during exercise, implying an elevated pulmonary vascular resistance (PVR) in DM + HC + CKD swine (153 ± 10 vs. 122 ± 9 mmHg∙L−1∙min∙kg). Phosphodiesterase 5 inhibition and endothelin receptor antagonism decreased PVR in DM + HC + CKD (− 12 ± 12 and − 22 ± 7 mmHg∙L−1∙min∙kg) but not in Healthy swine (− 1 ± 12 and 2 ± 14 mmHg∙L−1∙min∙kg), indicating increased vasoconstrictor influences of phosphodiesterase 5 and endothelin. Inhibition of nitric oxide synthase produced pulmonary vasoconstriction that was similar in Healthy and DM + HC + CKD swine, but unmasked a pulmonary vasodilator effect of endothelin receptor antagonism in Healthy (− 56 ± 26 mmHg∙L−1∙min∙kg), whereas it failed to significantly decrease PVR in DM + HC + CKD, indicating loss of nitric oxide mediated inhibition of endothelin in DM + HC + CKD. Scavenging of reactive oxygen species (ROS) had no effect on PVR in either Healthy or DM + HC + CKD swine. Cardiovascular magnetic resonance imaging, under anesthesia, showed no right ventricular changes. Finally, despite an increased contribution of endogenous nitric oxide to vasomotor tone regulation in the systemic vasculature, systemic vascular resistance at rest was higher in DM + HC + CKD compared to Healthy swine (824 ± 41 vs. 698 ± 35 mmHg∙L−1∙min∙kg). ROS scavenging induced systemic vasodilation in DM + HC + CKD, but not Healthy swine. In conclusion, common comorbidities directly alter pulmonary vascular control, by enhanced PDE5 and endothelin-mediated vasoconstrictor influences, well before overt left ventricular backward failure or pulmonary hypertension develop.

Assessment of myocardial strain using cardiac magnetic resonance (CMR) tissue tracking provides prognostic information incremental to left ventricular ejection fraction and allows for detailed analysis of regional myocardial deformation. This study sought to evaluate the effect of percutaneous

AIMS: This study aimed to evaluate associations between coronary collaterals and myocardial viability as assessed by quantitative cardiac magnetic resonance (CMR) imaging in patients with a chronic coronary total occlusion (CTO). METHODS AND RESULTS: A total of 218 patients with a CTO who underwent CMR between 2013 and 2018 were included. A concomitant collateral connection (CC) score 2 and Rentrop grade 3 defined well-developed collaterals in 146 (67%) patients, whereas lower CC scores or Rentrop grades characterised poorly developed collaterals. Dysfunctional myocardium (50%) was observed in only 5% of CTO segments. In the CTO territory, SWT was greater (3.72±1.51 vs 3.05±1.60 mm, p

Acute medial dissection of aorta can occur in the context of a sudden and unexpected death. For medico-legal reasons it is important to estimate as accurately the histological age of dissections. We evaluated the additional value of a systematic application of immunohistochemistry, compared with conventional histology only, in determining chronological steps of injury and repair. Thirty two paraffin embedded specimens of aortic dissection were retrospectively allocated to one of four defined stages: acute (I), subacute (II), early organizing (III) and scarring (IV) using Hematoxylin and Eosin and Elastica van Gieson stained sections. Subsequent immunohistochemically staining was performed with the following markers: (myeloperoxidase (neutrophils), citrullinated-Histone 3 (neutrophil extracellular traps), CD68 (macrophages), CD3 (T-cells), CD31 and CD34 (endothelial cells), and smooth muscle actin. Immune stained sections were scored semi-quantitatively. Histologically, five cases were identified as stage I, 16 as II, 7 as III and 4 as IV. Additional immunostaining for smooth muscle cells and endothelial cells altered the classification in 25% of cases (all in groups II and III). Immunostaining and semi-quantitative grading of involvement of neutrophils, macrophages and NETs also provided specific distribution patterns over the 4 age categories, including unexpected involvement of the peri adventitial fat tissue. In conclusion, it appears that semi-quantitative immunohistochemistry of resident vascular wall cells, inflammatory cells and NETS represents a useful adjunct in detailed histopathological grading of the chronological age of aortic dissections.

Heart failure with a preserved ejection fraction (HFpEF) is associated with multiple comorbidities, such as old age, hypertension, type 2 diabetes and obesity and is more prevalent in females. Although the male obese ZSF1 rat has been proposed as a suitable model to study the development of diastolic dysfunction and early HFpEF, studies in female animals have not been performed yet. Therefore, we aimed to characterize the cardiac phenotype in female obese ZSF1 rats and their lean counterparts. Additionally, we aimed to investigate whether differences exist in disease progression in obese male and female ZSF1 rats. Therefore, male and female ZSF1 rats, lean as well as obese (N = 6-9/subgroup), were used. Every two weeks, from 12 to 26 weeks of age, systolic blood pressure and echocardiographic measurements were performed, and venous blood was sampled. Female obese ZSF1 rats, as compared to female lean ZSF1 rats, developed diastolic dysfunction with cardiac hypertrophy and fibrosis in the presence of severe dyslipidemia, increased plasma growth differentiation factor 15 and mild hypertension, and preservation of systolic function. Although obese female ZSF1 rats did not develop hyperglycemia, their diastolic dysfunction was as severe as in the obese males. Taken together, the results from the present study suggest that the female obese ZSF1 rat is a relevant animal model for HFpEF with multiple comorbidities, suitable for investigating novel therapeutic interventions.

Comorbidities of ischemic heart disease, including diabetes mellitus (DM), hypercholesterolemia (HC) and chronic kidney disease (CKD), are associated with coronary microvascular dysfunction (CMD). Increasing evidence suggests that CMD may contribute to myocardial ‘Ischemia and No Obstructive Coronary Artery disease’ (INOCA). In the present study, we tested the hypothesis that CMD results in perturbations in myocardial perfusion and oxygen delivery using a novel swine model with multiple comorbidities. DM (streptozotocin), HC (high-fat diet) and CKD (renal embolization) were induced in 10 female swine (DM + HC + CKD), while 12 healthy female swine on a normal diet served as controls (Normal). After 5 months, at a time when coronary atherosclerosis was still negligible, myocardial perfusion, metabolism, and function were studied at rest and during treadmill exercise. DM + HC + CKD animals showed hyperglycemia, hypercholesterolemia, and impaired kidney function. During exercise, DM + HC + CKD swine demonstrated perturbations in myocardial blood flow and oxygen delivery, necessitating a higher myocardial oxygen extraction—achieved despite reduced capillary density—resulting in lower coronary venous oxygen levels. Moreover, myocardial efficiency was lower, requiring higher oxygen consumption for a given level of myocardial work. These perturbations in myocardial oxygen balance were associated with lower myocardial lactate consumption, stroke volume, and LVdP/dtmax, suggestive of myocardial ischemia and dysfunction. Further analyses showed a reduction in adenosine-recruitable coronary flow reserve, but this was exclusively the result of an increase in basal coronary blood flow, while maximal coronary flow per gram of myocardium was maintained; the latter was consistent with the unchanged arteriolar wall/lumen ratio, arteriolar density and peri-arteriolar collagen content. However, isolated small arteries displayed selective blunting of endothelium-dependent vasodilation in response to bradykinin in DM + HC + CKD swine, suggesting that changes in coronary microvascular function rather than in structure contributed to the perturbations in myocardial oxygen delivery. In conclusion, common comorbidities in swine result in CMD, in the absence of appreciable atherosclerosis, which is severe enough to produce perturbations in myocardial oxygen balance, particularly during exercise, resembling key features of INOCA. Electronic supplementary material The online version of this article (10.1007/s00395-020-0778-2) contains supplementary material, which is available to authorized users.

Introduction The prevalence of the junctional ST-depression with tall symmetrical T-waves in a field triage system for ST-Elevation Myocardial Infarction (STEMI) is unknown. Material and methods We prospectively collected all transmitted 12-lead electrocardiograms (ECGs) from the STEMI field triage system in Amsterdam from 2011 to 2013. Electrocardiograms with junctional ST-depression with tall symmetrical T-waves were recognized and angiographic documentation and clinical follow up were collected. Results A total of 5588 patients with at least 1 transmitted field ECG were identified from the database. ST-elevation infarction was present on the field ECG in 1864 patients (33%) and 701 ECGs (12,5%) showed anterior infarction. In 11 patients, junctional ST-depression with tall symmetrical T-waves was identified (0,2% of total transmitted ECGs and 1,6% of anterior infarctions). The 11 angiograms invariably showed involvement of the proximal Left Anterior Descending (LAD) artery (segment 5,6 and 7). Mortality was 27% within the first week. Conclusions An ECG with junctional ST-depression with tall symmetrical T-waves is an infrequent finding. Because this pattern of STEMI equivalent is associated with LAD occlusions, it is important to recognize this pattern, so patients can be transported to the catheterization laboratory without delay.

A myocardial ischemic burden (IB) of 10% or more denotes high risk patients who benefit from revascularization. This threshold has been assessed by SPECT, the higher resolution of PET presumably results in a better detection of the extent and severity of ischemia. As such, a PET-derived IB might

Current guidelines advocate viability assessment before revascularization of chronic coronary total occlusions (CTO). The present study evaluated associations between coronary collaterals and myocardial viability assessed by cardiac magnetic resonance (CMR) imaging in patients with a CTO. Patients

Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20–22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats. While we did not observe changes in basal synaptic transmission onto LII/III pyramidal cells in the mPFC of APO-SUS compared to APO-UNSUS rats, we report reduced paired-pulse ratios at longer inter-stimulus intervals. The GABAB receptor antagonist CGP 55845 abolished this reduction, indicating that the decreased paired-pulse ratio was caused by increased GABAB signaling. Consistently, we find an increased expression of the GABAB1 receptor subunit in APO-SUS rats. Our data provide physiological evidence for increased presynaptic GABAB signaling in the mPFC of APO-SUS rats, further supporting an important role for the GABAergic system in the pathophysiology of schizophrenia.

Timely reperfusion therapy by means of primary percutaneous coronary intervention (PCI) is the preferred treatment for patients with ST-segment elevation myocardial infarction. A significant number of patients with large acute myocardial infarction, caused by occlusion of an epicardial coronary artery, do not show ST-elevation on the electrocardiogram. Other ECG abnormalities may be present, the so called STEMI-equivalents. One such STEMI equivalent, junctional ST-segment depression followed by tall symmetrical T-waves in the precordial leads, often in combination with slight ST-elevation in lead AVR, has been associated with proximal occlusion of the left anterior descending coronary artery. Recognition of this ECG pattern by ambulance staff, emergency physicians and interventional cardiologists envolved in STEMI networks, is important to ensure timely reperfusion therapy in these patients. In this paper we present three patients with typical symptoms of acute myocardial infarction and the ECG pattern with slight J-point depression combined with tall, symmetrical T-waves.

1 case-controlled retrospective analysis compared the "two bag system," based on the euglycemic clamp technique, versus the traditional "one bag" method for intravenous diabetic ketoacidosis management. The two bag system can provide more cost-effective intravenous dextrose and fluid delivery and enhance quality of care by improving the efficiency, timeliness, and flexibility of overall control.

Deficits in sensorimotor gating measured by prepulse inhibition (PPI) of the startle have been known as characteristics of patients with schizophrenia and related neuropsychiatric disorders. PPI disruption is thought to rely on the activity of the mesocorticolimbic dopaminergic system and is inhibited by most antipsychotic drugs. These drugs however act also at the nigrostriatal dopaminergic pathway and exert adverse locomotor responses. Finding a way to inhibit the mesocorticolimbic- without affecting the nigrostriatal-dopaminergic pathway may thus be beneficial to antipsychotic therapies. The melanin-concentrating hormone (MCH) system has been shown to modulate dopamine-related responses. Its receptor (MCH1R) is expressed at high levels in the mesocorticolimbic and not in the nigrostriatal dopaminergic pathways. Interestingly a genomic linkage study revealed significant associations between schizophrenia and markers located in the MCH1R gene locus. We hypothesize that the MCH system can selectively modulate the behavior associated with the mesocorticolimbic dopamine pathway. Using mice, we found that central administration of MCH potentiates apomorphine-induced PPI deficits. Using congenic rat lines that differ in their responses to PPI, we found that the rats that are susceptible to apomorphine (APO-SUS rats) and exhibit PPI deficits display higher MCH mRNA expression in the lateral hypothalamic region and that blocking the MCH system reverses their PPI deficits. On the other hand, in mice and rats, activation or inactivation of the MCH system does not affect stereotyped behaviors, dopamine-related responses that depend on the activity of the nigrostriatal pathway. Furthermore MCH does not affect dizocilpine-induced PPI deficit, a glutamate related response. Thus, our data present the MCH system as a regulator of sensorimotor gating, and provide a new rationale to understand the etiologies of schizophrenia and related psychiatric disorders.