Risk stratification in patients with structurally normal hearts: Does fibrosis type matter?

OBJECTIVES: The study sought to assess the prognostic significance of nonischemic myocardial fibrosis (MF) on cardiovascular magnetic resonance (CMR)-both macroscopic MF assessed by late gadolinium enhancement (LGE) and diffuse microscopic MF quantified by extracellular volume fraction (ECV)-in patients with structurally normal hearts. BACKGROUND: The clinical relevance of tissue abnormalities identified by CMR in patients with structurally normal hearts remains unclear. METHODS: Consecutive patients undergoing CMR were screened for inclusion to identify those with LGE imaging and structurally normal hearts. ECV was calculated in patients with available T1 mapping. The associations between myocardial fibrosis and the outcomes of all-cause mortality, new-onset heart failure [HF], and an arrhythmic outcome were evaluated. RESULTS: In total 525 patients (mean age 43.1±14.2 years; 30.5% males) were included. Over a median follow-up of 5.8 years, 13 (2.5%) patients died and 18 (3.4%) developed new-onset HF. Nonischemic midwall /subepicardial LGE was present in 278 (52.9%) patients; isolated RV insertion fibrosis was present in 80 (15.2%) patients. In 276 patients with available T1 mapping, the mean ECV was 25.5 ± 4.4%. There was no significant association between LGE and all-cause mortality (HR: 1.36, CI: 0.42-4.42, p = 0.61), or new-onset HF (HR: 0.64, CI: 0.25-1.61, p = 0.34). ECV (per 1% increase) correlated with all-cause mortality (HR: 1.19, CI: 1.04-1.36, p = 0.009), but not with new-onset HF (HR: 0.97, CI: 0.86-1.10, p = 0.66). There was no significant association between arrhythmic outcomes and LGE (p = 0.60) or ECV (p = 0.49). In a multivariable model after adjusting for covariates, ECV remained significantly associated with all-cause mortality (HR per 1% increase in ECV: 1.26, CI: 1.06-1.50, p = 0.009). CONCLUSION: Nonischemic LGE in patients with structurally normal hearts is common and does not appear to be associated with adverse outcomes, whereas elevated ECV is associated with all-cause mortality and may be an important risk stratification tool.

Investigation into Polyphenol Profile and Biological Activities of Enriched Persimmon/Apple Smoothies during Storage.

Smoothies are becoming an increasingly popular product as a healthy alternative to snacks. The consumer expects from this product that, apart from its nutritional value, it will also be qualitatively stable during storage. Therefore, in this study, original smoothies obtained with persimmon fruit puree and apple juice (Dk/Md) enriched with Arbutus unedo fruits, Myrtus communis purple berry extract, Acca sellowiana, and Crocus sativus petal juice were evaluated for their polyphenol composition, antioxidant activity, and inhibition on targeted digestive enzymes, over six months of storage. The amount of polyphenols evaluated by UPLC-PDA analysis decreased in six months from 23.5% for both Dk/Md and enriched C. sativus smoothies to 42.5% for enriched A. sellowiana, with anthocyanins the most sensitive compounds (71.7-100% loss). Values of antioxidant assays generally strongly decreased during the first three months (up to ca. 60%) and to a lesser extent in the following three months (0.4-27%). In addition, inhibitory activity on α-amylase, α-glucosidase, and pancreatic lipase, especially on the last two enzymes, was negatively affected by time storage. The outcome of this study indicates that persimmon fruit is a good option for producing smoothies, and enrichment with other plant extracts can enhance the bioactive compound content and biological activities. It is recommended that appropriate storage strategies to preserve the properties of those smoothies should be developed.

Parametric mapping by cardiovascular magnetic resonance imaging in sudden cardiac arrest survivors.

Etiology of sudden cardiac arrest (SCA) is identified in less than 30% of survivors without coronary artery disease. We sought to assess the diagnostic role of myocardial parametric mapping using cardiovascular magnetic resonance (CMR) in identifying SCA etiology. Consecutive SCA survivors undergoing CMR with myocardial parametric mapping were included in the study. The determination if CMR was decisive or contributory in identifying SCA etiology was made if the diagnosis was unclear prior to CMR, and the discharge diagnosis was consistent with the CMR result. Parametric mapping was considered essential for establishing probable SCA etiology by CMR if the SCA cause could not have been determined without its utilization. If the CMR diagnosis could have been potentially based on the combination of cine and LGE imaging, parametric mapping was considered contributory. Of the 35 patients (mean age 46.9 ± 14.1 years; 57% males) included, SCA diagnosis was based on CMR in 23 (66%) patients. Of those, parametric mapping was essential for the diagnosis of myocarditis and tako-tsubo cardiomyopathy (11/48%) and contributed to the diagnosis in 10 (43%) additional cases. Inclusion of quantitative T1 and T2 parametric mapping in the SCA CMR protocol has the potential to increase diagnostic yield of CMR and further specify SCA etiology, especially myocarditis.

Comparison of Different Green Extraction Techniques Used for the Extraction of Targeted Flavonoids from Edible Feijoa (Acca sellowiana (O.Berg) Burret) Flowers.

This study aimed to investigate the effect of four green extraction techniques (ultrasound-assisted extraction, UAE; supercritical fluid extraction, SFE; subcritical water extraction, SWE; and extraction using deep eutectic solvents, DES) on the extraction of targeted flavonoids from edible feijoa flowers. The bioactive components in the obtained extracts were quantified by High-Performance Liquid Chromatography-Photodiode Array Detector (HPLC-PDA). Moreover, total polyphenol content and antioxidant activity by DPPH•, ABTS•+, FRAP, and CUPRAC assays were investigated. UAE generally gave the highest yields for isoquercitrin and quercetin content (18.36-25.33 and 10.86-16.13 µg/g), while DES extraction with choline chloride:lactic acid (1:2) and H2O content of 50% gave the highest yield of chrysanthemin (90.81 µg/g). The highest yield of flavone (12.69 mg/g) was obtained with supercritical CO2 at 300 bar. Finally, UAE gave the highest total polyphenol content (ca. 64 mg GAE/g) and antioxidant activity at 70 °C during 30 min with 40% (0.84 mmol TEAC/g and 2.25 mmol Fe2+/g, for ABTS•+ and CUPRAC, respectively) and 60% ethanol-water solution (0.49 mmol TEAC/g and 2.09 mmol Fe2+/g, for DPPH• and FRAP, respectively). The eco-friendly extraction techniques resulted in selective methods capable of extracting targeted bioactive compounds from edible feijoa flowers.

Antioxidant Activity and Inhibition of Digestive Enzymes of New Strawberry Tree Fruit/Apple Smoothies.

In this study, original smoothies obtained with strawberry tree fruit puree and apple juice enriched with Diospyros kaki fruits, Myrtus communis purple berry extract, Acca sellowiana, and Crocus sativus petal juice were evaluated for their antioxidant activity and inhibition of targeted digestive enzymes. Values of CUPRAC, FRAP, ORAC, DPPH•, and ABTS•+ assays generally increased with plant enrichment, particularly for A. sellowiana addition (ABTS•+ 2.51 ± 0.01 mmol Trolox/100 g fw). The same trend was observed regarding the ability to scavenge reactive oxygen species (ROS) tested in Caco-2 cell cultures. Inhibitory activity on α-amylase and α-glucosidase was increased by D. kaki, M. communis, and A. sellowiana. Total polyphenols evaluated by UPLC-PDA analysis ranged between 535.75 ± 3.11 and 635.96 ± 5.21 mg/100 g fw, and A. sellowiana provided the higher amount. Flavan-3-ols accounted for more than 70% of phenolic compounds, and only smoothies enriched with C. sativus showed a high amount of anthocyanins (25.12 ± 0.18 mg/100 g fw). The outcome of this study indicates these original smoothies as a possible ally in counteracting oxidative stress, as established by their favourable antioxidant compound profile, thus suggesting an interesting future application as nutraceuticals.

T2 mapping in myocardial disease: a comprehensive review.

Cardiovascular magnetic resonance (CMR) is considered the gold standard imaging modality for myocardial tissue characterization. Elevated transverse relaxation time (T2) is specific for increased myocardial water content, increased free water, and is used as an index of myocardial edema. The strengths of quantitative T2 mapping lie in the accurate characterization of myocardial edema, and the early detection of reversible myocardial disease without the use of contrast agents or ionizing radiation. Quantitative T2 mapping overcomes the limitations of T2-weighted imaging for reliable assessment of diffuse myocardial edema and can be used to diagnose, stage, and monitor myocardial injury. Strong evidence supports the clinical use of T2 mapping in acute myocardial infarction, myocarditis, heart transplant rejection, and dilated cardiomyopathy. Accumulating data support the utility of T2 mapping for the assessment of other cardiomyopathies, rheumatologic conditions with cardiac involvement, and monitoring for cancer therapy-related cardiac injury. Importantly, elevated T2 relaxation time may be the first sign of myocardial injury in many diseases and oftentimes precedes symptoms, changes in ejection fraction, and irreversible myocardial remodeling. This comprehensive review discusses the technical considerations and clinical roles of myocardial T2 mapping with an emphasis on expanding the impact of this unique, noninvasive tissue parameter.

HR-LC-ESI-Orbitrap-MS-Based Metabolic Profiling Coupled with Chemometrics for the Discrimination of Different Echinops spinosus Organs and Evaluation of Their Antioxidant Activity.

This study aimed to assess and correlate the phenolic content and the antioxidant activity of the methanol extracts of the stems, roots, flowers, and leaves of Echinops spinosus L. from north-eastern Algeria. Qualitative analysis was performed by high-resolution mass spectrometry (HR) LC-ESI-Orbitrap-MS and (HR) LC-ESI-Orbitrap-MS/MS). Forty-five compounds were identified in the methanol extracts; some are described for the first time in E. spinosus. Targeted phenolic compounds were quantified by HPLC-DAD and it was shown that caffeoyl quinic derivatives were the most abundant compounds. Chemometric analysis was performed using principal component analysis (PCA) and hierarchical cluster analysis (HCA) based on the qualitative and quantitative LC data. The score plot discriminates different Echinopsis spinosus organs into three distinct clusters, with the stems and flowers allocated in the same cluster, reflecting their resemblance in their secondary metabolites. The antioxidant activities of the methanol extracts were assessed using cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant assay (FRAP), diphenyl picryl hydrazyl radical-scavenging capacity assay (DPPH●), and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS●+). The root extract exhibited the highest antioxidant activity, evidenced by 3.26 and 1.61 mmol Fe2+/g dried residue for CUPRAC and FRAP, respectively, and great free radical-scavenging activities estimated by 0.53 and 0.82 mmol TEAC/g dried residue for DPPH● and ABTS●+, respectively. The methanol extract of the roots demonstrated a significant level of total phenolics (TP: 125.16 mg GAE/g dried residue) and flavonoids (TFI: 25.40 QE/g dried residue TFII: 140 CE/g dried residue). Molecular docking revealed that tricaffeoyl-altraric acid and dicaffeoyl-altraric acid exhibited the best fit within the active sites of NADPH oxidase (NO) and myeloperoxidase (MP). From ADME/TOPAKT analyses, it can be concluded that tricaffeoyl-altraric acid and dicaffeoyl-altraric acid also revealed reasonable pharmacokinetic and pharmacodynamic characteristics with a significant safety profile.

Anti- and Pro-Oxidant Activity of Polyphenols Extracts of Syrah and Chardonnay Grapevine Pomaces on Melanoma Cancer Cells.

The phenolic composition of Syrah and Chardonnay grape pomaces was studied to assess their antioxidant and prooxidant properties. Polyphenols were extracted by a "green" hydroalcoholic solvent (ethanol/water 1:1 v/v), and a detailed chemical and electrochemical characterization of the phenolic compounds was performed. The antioxidant and prooxidant capacity of the pomace was first studied by cyclic voltammetry (CV) and other reference analytical assays, then with biological tests on B16F10 metastatic melanoma cancer cells. Electrochemical data showed that, when a +0.5 V potential was applied, a low to moderate antioxidant capacity was observed. MTT test showed an increasing viability of melanoma cells, after treatments at low concentration (up to 100 µg/mL) and for a short time (6 h), but when cells were treated with higher doses of extract (≥250 µg/mL for 12/24 h), their viability decreased from 25 to 50% vs. control, depending on treatment time, dose, and extract origin. A stronger prooxidant activity resulted when 250 µg/mL of extract was combined with non-toxic doses of H2O2; this activity was correlated with the presence of copper in the extracts. This study shows the potential of winemaking by-products and suggests the opportunity to exploit them for the production of cosmeceuticals, or for combined therapies with approved anticancer drugs.

Effect of Apple Juice Enrichment with Selected Plant Materials: Focus on Bioactive Compounds and Antioxidant Activity.

Using a multi-analytical approach, this paper aimed to investigate the effect of apple juice enrichment with Arbutus unedo and Diospyros kaki fruits, Myrtus communis berry extract, Acca sellowiana, or Crocus sativus flower by-products on both bioactive compounds content and antioxidant activity. Physico-chemical parameters, vitamin C, sugars, organic acids, total polyphenol content, antioxidant activity, and sensory attributes were evaluated. An LC-PDA/MS QTof analysis allowed for the identification of 80 different phenolic compounds. The highest polyphenol content (179.84 and 194.06 mg of GAE/100 g fw) and antioxidant activity (CUPRAC, 6.01 and 7.04 mmol of Fe2+/100 g fw) were observed in products with added A. sellowiana and D. kaki, respectively. Furthermore, the study showed a positive correlation between polymeric procyanidins and antioxidant activity (0.7646-0.8539). The addition of A. unedo fruits had a positively significant influence on the increment of vitamin C (23.68 ± 0.23 mg/100 g fw). The obtained products were attractive to consumers, especially those with 0.1% C. sativus flower juice, M. communis berry extract, and persimmon D. kaki fruits. The synergy among the different analytical techniques allowed us to obtain a complete set of information, demonstrating that the new apple smoothies were enriched in both different beneficial molecules for human health and in antioxidant activity.

Evaluation of bioactive compounds and antioxidant capacity of edible feijoa (Acca sellowiana (O. Berg) Burret) flower extracts.

ABSTRACT: The research aimed to evaluate the polyphenolic composition and the antioxidant capacity of edible extracts of feijoa (Acca sellowiana (O. Berg) Burret) flowers. Phenolic compounds of whole feijoa flower (FM), feijoa petals (PM) and feijoa petals juice (PJ) were identified by high-performance liquid chromatography coupled with electrospray mass spectrometry and quantified by liquid chromatography coupled with ultraviolet/visible detection. Moreover, the total polyphenol (TP) content was measured spectrophotometrically and the antioxidant capacities of the extracts were evaluated by FRAP, CUPRAC, DPPH·, and ABTS·+ assays. The FM showed TP content (395.14 ± 7.91 mg GAE/L) higher than PM and PJ, and exhibited better antioxidant capacities. FM extracts were characterized by the high content of anthocyanins (115.3 ± 3.6 mg/L), flavonols (42.9 ± 3.3 mg/L) and the presence of ellagic acid (7.9 ± 0.2 mg/L) and other galloyltannins. In addition, cyanidin-3-O-glucoside and apigenin were detected in all the three extracts. The present study provided an overview on particular bioactive compounds that characterise different parts of edible feijoa flowers. Among the latter, FM proved to be the most suitable for exploitation in the food and health manufactory.

Patterns of desmin expression in idiopathic dilated cardiomyopathy are related to the desmin mRNA and ubiquitin expression.

Desmin expression depends on desmin messenger RNA (mRNA) and ubiquitin proteasome system. This process is poorly understood in dilated cardiomyopathy. The aim of the study was to investigate whether changes of desmin mRNA and ubiquitin expression correlate with types of desmin expression in cardiomyocytes. Endomyocardial biopsy was performed in 60 patients (85% men, mean age 46±14 years) with heart failure (HF; left ventricular ejection fraction <45%). Desmin and ubiquitin expression were analysed in histological sections by immunohistochemistry and in Western blot. Desmin mRNA expression was determined by fluorescent in situ hybridization methods. In patients with weak/even desmin expression, weak/even expression of ubiquitin in the cytosol and low desmin mRNA expression in the cytosol and nuclei of cardiomyocytes were observed. Expression of ubiquitin and desmin mRNA increased along with the progression of desmin cytoskeleton remodeling. Desmin mRNA and ubiquitin were weakly expressed/absent in cardiomyocytes with low/lack of desmin expression. Variations in desmin mRNA, desmin and ubiquitin expression were associated with gradual changes in myocardial structure and clinical parameters. To conclude, changes in ubiquitin and desmin mRNA expression are related to patterns of desmin expression. An increase in the expression of ubiquitin and desmin mRNA may be a protective feature against unfavorable cell remodeling. This may reduce the adverse effects of cytoskeleton damage in the early stages of HF. Low/lack ubiquitin and/or desmin mRNA expression may be markers of end-stage HF.

Comparative assessment of three drug eluting stents with different platforms but with the same biodegradable polymer and the drug based on quantitative coronary angiography and optical coherence tomography at 12-month follow-up.

The aim of this study was to compare neointima proliferation in three drug-eluting stents (DES) produced by the same company (Balton, Poland) which are covered with a biodegradable polymer and elute sirolimus (concentration: 1.0 and 1.2 µg/mm2), but have different stent platforms and strut thickness: stainless steel Prolim® (115 µm) and BiOSS LIM® (120 µm) and cobalt-chromium Alex® (70 µm). We analyzed data of patients with quantitative coronary angiography (QCA) and optical coherence tomography (OCT) at 12 months from BiOSS LIM Registry, Prolim Registry and Alex OCT clinical trial. There were 56 patients enrolled, in whom 29 Prolim® stents were deployed, in 11-BiOSS LIM® and in 16-Alex stents. The late lumen loss was the smallest in Prolim® subgroup (0.26 ± 0.17 mm) and did not differ from Alex® subgroup (0.28 ± 0.47 mm). This parameter was significantly bigger in BiOSS® subgroup (0.38 ± 0.19 mm; p < 0.05). In OCT analysis there was no statistically significant difference between Prolim® and Alex® subgroups in terms of mean neointima burden (24.6 ± 8.6 vs. 19.27 ± 8.11%) and neointima volume (28.16 ± 15.10 vs. 24.51 ± 17.64 mm3). In BiOSS® group mean neointima burden (30.9 ± 6.2%) and mean neointima volume (44.9 ± 4.9 mm3) were significantly larger. The morphological analysis revealed that in most cases in all groups the neointima was homogenous with plaque presence only around stent struts. In the QCA and OCT analysis regular DES (Prolim® and Alex®) obtained similar results, whereas more pronounced response from the vessel wall was found in the BiOSS® subgroup.

Comparative assessment of three drug eluting stents with different platforms but with the same biodegradable polymer and the drug based on quantitative coronary angiography and optical coherence tomography at 12-month follow-up

The aim of this study was to compare neointima proliferation in three drug-eluting stents (DES) produced by the same company (Balton, Poland) which are covered with a biodegradable polymer and elute sirolimus (concentration: 1.0 and 1.2 µg/mm2), but have different stent platforms and strut thickness: stainless steel Prolim® (115 µm) and BiOSS LIM® (120 µm) and cobalt-chromium Alex® (70 µm). We analyzed data of patients with quantitative coronary angiography (QCA) and optical coherence tomography (OCT) at 12 months from BiOSS LIM Registry, Prolim Registry and Alex OCT clinical trial. There were 56 patients enrolled, in whom 29 Prolim® stents were deployed, in 11-BiOSS LIM® and in 16-Alex stents. The late lumen loss was the smallest in Prolim® subgroup (0.26 ± 0.17 mm) and did not differ from Alex® subgroup (0.28 ± 0.47 mm). This parameter was significantly bigger in BiOSS® subgroup (0.38 ± 0.19 mm; p < 0.05). In OCT analysis there was no statistically significant difference between Prolim® and Alex® subgroups in terms of mean neointima burden (24.6 ± 8.6 vs. 19.27 ± 8.11%) and neointima volume (28.16 ± 15.10 vs. 24.51 ± 17.64 mm3). In BiOSS® group mean neointima burden (30.9 ± 6.2%) and mean neointima volume (44.9 ± 4.9 mm3) were significantly larger. The morphological analysis revealed that in most cases in all groups the neointima was homogenous with plaque presence only around stent struts. In the QCA and OCT analysis regular DES (Prolim® and Alex®) obtained similar results, whereas more pronounced response from the vessel wall was found in the BiOSS® subgroup.

Evaluation of natural occurring bioactive compounds and antioxidant activity in Nuragus white wines.

The aim of the present study is to highlight volatile and targeted non-volatile bioactive compounds in Nuragus wines, as a part of Italian DOC (Controlled Origin Designation) white wines. So far there has not been any systematic study of the chemical compositions and antioxidant activity of this monovarietal wine. Phenolic compounds, volatiles and organic acids were analysed and antioxidant capacity was assessed by spectrophotometric assays. Chromaticity coordinates and technological parameters (alcohol, reducing sugars, pH, total and volatile acidity) were also evaluated. Gallic acid (128±87mg/L), trans-caftaric acid (81±27mg/L) and tyrosol (25±8mg/L) were the most abundant phenolic compounds. The major headspace volatiles were isoamyl alcohol (35.8-76.6%) and 2-phenylethanol (5.9-24.9%). In the wine extracts, the most abundant were 2-phenylethanol (12.3-40.0%), 4-hydroxy-2-phenylethanol (12.5-33.3%), diethyl succinate (5.8-30.3%), (Z)-octadec-9-en-1-ol (5.9-18.3%) and tryptophol (2.8-15.6%). Nuragus wines exhibited an excellent antioxidant capacity. The data obtained may help Nuragus wine producers to promote this monovarietal wine as a valid complement associated with the Mediterranean diet.