Left main coronary artery compression in precapillary pulmonary hypertension.

Pulmonary hypertension (PH) is a progressive and invalidating condition despite available therapy. Addressing complications such as left main coronary artery compression (LMCo) due to the dilated pulmonary artery (PA) may improve symptoms and survival. Nevertheless, clear recommendations are lacking. The aim of this study is to analyze the prevalence, characteristics, predictive factors and impact of LMCo in a heterogenous precapillary PH population in a single referral center. Two hundred sixty-five adults with various etiologies of precapillary PH at catheterization were reviewed. Coronary angiography (CA) was performed for LMCo suspicion. Revascularization was performed in selected cases. Outcomes were assessed at a mean follow-up of 3.9 years. LMCo was suspected in 125 patients and confirmed in 39 (31.2%), of whom 21 (16.8%) had 50%-90% stenoses. Nine revascularizations were performed, with clinical improvement. The only periprocedural complication was a stent migration. LMCo was associated with PH etiology (p 0.003), occuring more frequently in congenital heart disease-associated PH (61.5% of all LMCo cases, 66.6% of LMCo ≥ 50%). Predictors of LMCo ≥50% were PA ≥ 37.5 mm (Sn 81%, Sp 74%) and PA-to-aorta ≥1.24 (Sn 81%, Sp 69%), with increased discrimination when considering RV end-diastolic area. LMCo ≥ 50% without revascularization presented clinical deterioration and worse survival (p 0.019). This analysis of a heterogeneous pre-capillary PH population provides LMCo prevalence estimation, predictive factors (PA size, PA-to-aorta, RV end-diastolic area and PH etiology) and long-term impact. While LMCo impact on survival is inconclusive, untreated LMCo ≥ 50% has worse prognosis. LMCo revascularization may be performed safely and with good outcomes.

Left main coronary artery compression by dilated pulmonary artery in pulmonary arterial hypertension: a systematic review and meta-analysis.

OBJECTIVE: Pulmonary arterial hypertension (PAH) can lead to left main coronary artery compression (LMCo), but data on the impact, screening and treatment are limited. A meta-analysis of LMCo cases could fill the knowledge gaps in this topic. METHODS: Electronic databases were searched for all LMCo/PAH studies, abstracts and case reports including pulmonary artery (PA) size. Restricted maximum likelihood meta-analysis was used to evaluate LMCo-associated factors. Specificity, sensitivity and accuracy of PA size thresholds for diagnosis of LMCo were calculated. Treatment options and outcomes were summarized. RESULTS: A total of five case-control cohorts and 64 case reports/series (196 LMCo and 438 controls) were included. LMCo cases had higher PA diameter (Hedge's g 1.46 [1.09; 1.82]), PA/aorta ratio (Hedge's g 1.1 [0.64; 1.55]) and probability of CHD (log odds-ratio 1.22 [0.54; 1.9]) compared to non-LMCo, but not PA pressure or vascular resistance. A 40 mm cut-off for the PA diameter had balanced sensitivity (80.5%), specificity (79%) and accuracy (79.7%) for LMCo diagnosis, while a value of 44 mm had higher accuracy (81.7%), higher specificity (91.5%) but lower sensitivity (71.9%). Pooled mortality after non-conservative treatment (n = 150, predominantly stenting) was 2.7% at up to 22 months of mean follow-up, with 83% survivors having no angina at follow-up. CONCLUSION: PA diameter, PA/aorta ratio and CHD are associated with LMCo, while hemodynamic parameters are not. Data from this study support that a PA diameter cut-off between 40 and 44 mm can offer optimal accuracy for LMCo screening. Preferred treatment was coronary stenting, associated with low mid-term mortality and symptom relief. Diagnosis and management of left main coronary artery compression (LMCo) in patients with pulmonary arterial hypertension (PAH).

Improving robustness of automatic cardiac function quantification from cine magnetic resonance imaging using synthetic image data.

Although having been the subject of intense research over the years, cardiac function quantification from MRI is still not a fully automatic process in the clinical practice. This is partly due to the shortage of training data covering all relevant cardiovascular disease phenotypes. We propose to synthetically generate short axis CINE MRI using a generative adversarial model to expand the available data sets that consist of predominantly healthy subjects to include more cases with reduced ejection fraction. We introduce a deep learning convolutional neural network (CNN) to predict the end-diastolic volume, end-systolic volume, and implicitly the ejection fraction from cardiac MRI without explicit segmentation. The left ventricle volume predictions were compared to the ground truth values, showing superior accuracy compared to state-of-the-art segmentation methods. We show that using synthetic data generated for pre-training a CNN significantly improves the prediction compared to only using the limited amount of available data, when the training set is imbalanced.

The Impact of COVID-19 Pandemic on the Interventional Cardiology Workload in Private Versus Public Hospitals of Romania in 2020.

The Covid-19 pandemic has severely affected and changed medical activity worldwide. Public hospitals have been suffocated by the large number of Covid-19 patients, sometimes making it difficult for patients with other conditions to be admitted to hospital. This was also true for patients with cardiovascular disease. In the present article we describe the main variations in the activity of interventional cardiology laboratories in Romania between the pre-pandemic year 2019 and the pandemic year 2020 in private and public hospitals.

Gradual Correction of Pediatric Equinus Deformity.

Pediatric equinus is broadly defined as generalized limited dorsiflexion at the ankle joint. It may result from either congenital or acquired causes and exhibit varying characteristics such as flexible, rigid, or spastic types. It has been extensively studied in literature and is known to be associated with the pathological condition of the bone, soft tissue, or combined deformity. In children, rigid plantarflexed cases can be debilitating and prevent them from ambulating without pain, if at all. As this volume in Clinics has chapters on comprehensive pediatric examination and neuromuscular disorders, this article will focus on (non-neurologic equinus) and its treatment via conservative and surgical methods with an emphasis on gradual correction.

Use of 3D rotational angiography to perform computational fluid dynamics and virtual interventions in aortic coarctation.

Computational fluid dynamics (CFD) can be used to analyze blood flow and to predict hemodynamic outcomes after interventions for coarctation of the aorta and other cardiovascular diseases. We report the first use of cardiac 3-dimensional rotational angiography for CFD and show not only feasibility but also validation of its hemodynamic computations with catheter-based measurements in three patients.

The Cytotoxic Properties of Some Tricyclic 1,3-Dithiolium Flavonoids.

BACKGROUND: Due to the emergence of multidrug resistant microorganisms, new classes of antibiotics are needed. In this paper, we present the cytotoxic effects of five tricyclic flavonoids, one of which was previously identified as a potent antimicrobial agent. METHODS: All five derivatives were tested against human HOS and MCF7 cancer cell lines using a wound scratch assay. The cytotoxic properties of previously reported flavonoid 4a were also evaluated using the standard MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) and live/dead assays, using NHDF, HOS and MCF7 cell lines. RESULTS: All five derivatives were found to inhibit to some degree the proliferation of cancer cells. 4a was also found to be less toxic towards regular versus cancerous human cells. Moreover, the minimum bactericidal concentration of 4a against Staphylococcus aureus was found to be non-toxic for any of the tested human cell lines. CONCLUSIONS: Derivative 4a has the potential of being used as a therapeutic agent against certain microorganisms. Further structure optimization is required for use against tumors.

Coronary CT Angiography-derived Fractional Flow Reserve: Machine Learning Algorithm versus Computational Fluid Dynamics Modeling.

Purpose To compare two technical approaches for determination of coronary computed tomography (CT) angiography-derived fractional flow reserve (FFR)-FFR derived from coronary CT angiography based on computational fluid dynamics (hereafter, FFRCFD) and FFR derived from coronary CT angiography based on machine learning algorithm (hereafter, FFRML)-against coronary CT angiography and quantitative coronary angiography (QCA). Materials and Methods A total of 85 patients (mean age, 62 years ± 11 [standard deviation]; 62% men) who had undergone coronary CT angiography followed by invasive FFR were included in this single-center retrospective study. FFR values were derived on-site from coronary CT angiography data sets by using both FFRCFD and FFRML. The performance of both techniques for detecting lesion-specific ischemia was compared against visual stenosis grading at coronary CT angiography, QCA, and invasive FFR as the reference standard. Results On a per-lesion and per-patient level, FFRML showed a sensitivity of 79% and 90% and a specificity of 94% and 95%, respectively, for detecting lesion-specific ischemia. Meanwhile, FFRCFD resulted in a sensitivity of 79% and 89% and a specificity of 93% and 93%, respectively, on a per-lesion and per-patient basis (P = .86 and P = .92). On a per-lesion level, the area under the receiver operating characteristics curve (AUC) of 0.89 for FFRML and 0.89 for FFRCFD showed significantly higher discriminatory power for detecting lesion-specific ischemia compared with that of coronary CT angiography (AUC, 0.61) and QCA (AUC, 0.69) (all P < .0001). Also, on a per-patient level, FFRML (AUC, 0.91) and FFRCFD (AUC, 0.91) performed significantly better than did coronary CT angiography (AUC, 0.65) and QCA (AUC, 0.68) (all P < .0001). Processing time for FFRML was significantly shorter compared with that of FFRCFD (40.5 minutes ± 6.3 vs 43.4 minutes ± 7.1; P = .042). Conclusion The FFRML algorithm performs equally in detecting lesion-specific ischemia when compared with the FFRCFD approach. Both methods outperform accuracy of coronary CT angiography and QCA in the detection of flow-limiting stenosis.

Tetrathiafulvalene-[2.2]paracyclophanes: Synthesis, crystal structures, and chiroptical properties.

Two racemic tetrathiafulvalene-[2.2]paracyclophane electron donors EDT-TTF-[2.2]paracyclophane 1 and (COOMe)2 -TTF-[2.2]paracyclophane 2 have been synthesized via the phosphite mediated cross coupling strategy. Chiral HPLC allowed the optical resolution of the (RP ) and (SP ) enantiomers for both compounds. Solid-state structures of (RP )-1 and (rac)-2 have been determined by single crystal X-ray analysis. Intermolecular π-π and S•••S interactions are disclosed in the packing. Single crystal X-ray analysis of (RP )-1 combined with experimental and theoretical circular dichroism spectra allowed the assignment of the absolute configuration of the enantiomers of 1 and 2.

[2.2]Paracyclophane-Bis(triazole) Systems: Synthesis and Photochemical Behavior.

Mono-, pseudo-gem, and pseudo-para ethynylcyclophanes and bis(azides) have been employed as addition partners in CuAAC reactions to design and build complex extended molecular scaffolds. The reactivity of the resulting triazoles was investigated under photochemical conditions. A variety of newly substituted [2.2]paracyclophanes were identified; deazotization of pseudo-gem and pseudo-para adducts provided indolophane derivatives. An intramolecular stabilization effect was observed in the case of pseudo-gem derivatives. A photochemical rearrangement from a pseudo-para adduct to a pseudo-ortho product was identified.

Antibacterial structure-activity relationship studies of several tricyclic sulfur-containing flavonoids.

A structure-activity relationship study concerning the antibacterial properties of several halogen-substituted tricyclic sulfur-containing flavonoids has been performed. The compounds have been synthesized by cyclocondensation of the corresponding 3-dithiocarbamic flavanones under acidic conditions. The influence of different halogen substituents on the antibacterial properties has been tested against Staphylococcus aureus and Escherichia coli. Amongst the N,N-dialkylamino-substituted flavonoids, those having an N,N-diethylamino moiety exhibited good to excellent antimicrobial properties against both pathogens. Fluorine-substituted flavonoids were found to be less active than those bearing other halogen atoms.

[2.2]Paracyclophane derivatives containing tetrathiafulvalene moieties.

The synthesis of [2.2]paracyclophane derivatives containing tetrathiafulvalene units has been accomplished by the coupling reaction of 4-([2.2]paracyclophan-4-yl)-1,3-dithiol-2-thione in the presence of trimethylphosphite. The 1,3-dithiol-2-thione derivative was in turn synthesized by the regioselective bromination of 4-acetyl[2.2]paracyclophane, then through the corresponding dithiocarbamates and 1,3-dithiolium salts.

Selenium halide-induced bridge formation in [2.2]paracyclophanes.

An addition/elimination sequence of selenium halides to pseudo-geminally bis(acetylene) substituted [2.2]paracyclophanes leads to new bridges with an endo-exo-diene substructure. The reactions have been found to be sensitive to the substitution of the ethynyl group. The formation of dienes with a zig-zag configuration is related to that observed for non-conjugated cyclic diynes of medium ring size.

A facile synthesis of Pechmann dyes.

A facile synthesis of Pechmann dyes has been accomplished by the reaction of substituted N-phenacyl-4-dimethylaminopyridinium halides with dimethyl maleate in the presence of DBU. Based on a related 4-DMAP elimination product and an isolated monolactone intermediate a reaction mechanism has been proposed. The scope of this synthetic method is determined by the availability of α-haloaroyl or heteroaroyl derivatives. DBU=1,8-diazabicycloundec-7-ene, DMAP=4-dimethylaminopyridine.

The antibacterial properties of sulfur containing flavonoids.

Some dithiocarbamic esters bearing a flavanone backbone, as well as their corresponding 1,3-dithiolium salts were tested against Staphylococcus aureus and Escherichia coli. The 1,3-dithiolium tricyclic flavonoids display good inhibitory properties against both Gram-positive and Gram-negative pathogens.

5-Bromo-4-(3,5-di-bromo-2-hy-droxy-phen-yl)-2-(piperidin-1-yl)-1,3-di-thiol-2-ylium bromide.

In the title salt, C14H13Br3NOS2 (+)·Br(-), synthesized by bromination of mesoionic 2-[2-(piperidin-1-yl)-1,3-di-thiol-2-ylium-4-yl]phenolate in glacial acetic acid, the dihedral angle between the 1,3-di-thiol-ium ring and the phenolic substituent ring is 45.9 (3)° due to the steric influence of the ortho-Br group on the 1,3-di-thiol-ium ring. The piperidine ring adopts a chair conformation. In the crystal, the cation and anion are linked by an O-H⋯Br hydrogen bond.

rac-1-(5-Bromo-2-hy-droxy-phen-yl)-1-oxopropan-2-yl morpholine-4-carbo-dithio-ate.

In the racemic title compound, C14H16BrNO3S2, synthesized from the corresponding ω-bromo-propio-phenone, the dihedral angle between the plane of the phenol group and that of the planar section [maximum deviation = 0.040 (2) Å] of the morpholine-4-carbodi-thiol-ate moiety is 76.36 (10)°. A strong intra-molecular phenol O-H⋯O hydrogen bond if present in the mol-ecule. In the crystal, only weak C-H⋯S and C-H⋯O inter-actions are found.

4-Bromo-2-[5-methyl-2-(morpholin-4-yl)-1,3-thia-zol-4-yl]phenol.

In the title compound, C14H15BrN2O2S, synthesized by the reaction of the corresponding phenacyl thio-cyanate with morpholine, the dihedral angle between the 1,3-thia-zole ring and the phenolic substituent ring is 23.46 (10)° as a result of the steric influence of the ortho-methyl group on the thia-zole ring. A strong intra-molecular phenolic O-H⋯N hydrogen bond is present in the mol-ecule. In the crystal, a weak C-H⋯Ophenol hydrogen bond gives rise to chains lying parallel to [20-1]. A short inter-molecular Br⋯Omorpholine inter-action is also present [3.1338 (19) Å].

Cutting the Gordian knot: the blockage of the jejunal tube, a rare complication of Duodopa infusion treatment.

We present the case of a 21-year-old man with advanced refractory Parkinson's disease treated with Duodopa continuous infusion. With this therapy, the patient had a spectacular recovery but after six months, he experienced an aggravation of his symptoms. A failure of his pumping system was suspected but we discovered that the jejunal tube was blocked due to a knot around a bezoar. This is the first complication of this kind described with the Duodopa infusion technique.