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Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with a high risk of sudden cardiac death. Three different prediction models for the indication of implanted cardioverter defibrillator (ICD) are now available: the 5 year ARVC risk score, the International Task Force Consensus (ITFC) criteria, and the Heart Rhythm Society (HRS) criteria. We compared these three prediction models in a validation cohort of patients with definite ARVC. Methods and results In a cohort of 140 patients with definite ARVC, the 5 year ARVC risk score and the ITFC and HRS criteria were compared for the prediction of a major combined endpoint of sudden cardiac death, appropriate ICD intervention, resuscitated cardiac arrest, and sustained ventricular tachycardia. During the follow‐up, 65 major events occurred. The 5 year ARVC risk score with a threshold >10%, derived from the maximally selected rank statistic, predicted 62 (95%) events [odds ratio (OR) 9.1, 95% confidence interval (CI) 2.6–32, P = 0.0006], the ITFC criteria 53 (81%, OR 4.8, 95% CI 2.2–10.3, P = 0.0001), and the HRS criteria 29 (45%, OR 4.2, 95% CI 1.9–9.3, P = 0.0003). At the analysis of decision curve for ICD implantation, a 5 year ARVC risk score >10% showed a greater net benefit than the ITFC and HRS criteria over a wide range of threshold probability of events. Finally, at multivariate analysis, the 5 year ARVC risk score >10% was the only independent predictor of major events. Conclusions The 5 year score with a threshold of >10% was more effective for predicting events than the ITFC and HRS criteria.

Aim To assess the prevalence and prognostic significance of NI-LGE in patients undergoing stress-CMR. Methods Stress-CMR with either dipyridamole or adenosine was performed in 283 patients (228 men, 81%) including perfusion imaging, wall motion evaluation and LGE. Follow-up was completed in all enrolled patients (median time: 1850 days; interquartile range: 1225-2705 days). Composite endpoint included cardiac death, ventricular tachycardia, myocardial infarction, stroke, hospitalization for cardiac cause and coronary revascularization performed beyond 90 days from stress-CMR scans. Results One hundred and twelve patients (40%) had negative LGE (no-LGE), 140 patients (49%) I-LGE and 31 patients (11%) NI-LGE. Twenty-five events occurred in the no-LGE group, 68 in I-LGE and 11 in the NI-LGE group. On survival curves, patients with NI-LGE had worse prognosis than patients with no-LGE regardless of the presence of inducible perfusion defects. No significant prognostic differences were found between I-LGE and NI-LGE. Conclusion NI-LGE can be detected in 11% of patients during stress-CMR providing a diagnosis of nonischemic cardiac disease. Patients with NI-LGE have worse prognosis than those with no-LGE.

Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating "anatomical" and "functional" information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future.

A mild light-driven protocol for the direct alkylation of phenols is reported. The process is driven by the photochemical activity of a halogen-bonded complex formed upon complexation of the in situ generated electron-rich phenolate anion with the α-iodosulfone. The reaction proceeds rapidly (10 min) under microfluidic conditions, delivering a wide variety of ortho-alkylated products (27 examples, up to 97% yield, >20:1 regioselectivity, on a gram scale), including densely functionalized bioactive phenol derivatives.

Restrictive cardiomyopathy (RCM) is a heterogeneous group of diseases characterized by restrictive left ventricular pathophysiology, i.e. a rapid rise in ventricular pressure with only small increases in filling volume due to increased myocardial stiffness. More precisely, the defining feature of RCM is the coexistence of persistent restrictive pathophysiology, diastolic dysfunction, non-dilated ventricles, and atrial dilatation, regardless of ventricular wall thickness and systolic function. Beyond this shared haemodynamic hallmark, the phenotypic spectrum of RCM is wide. The disorders manifesting as RCM may be classified according to four main disease mechanisms: (i) interstitial fibrosis and intrinsic myocardial dysfunction, (ii) infiltration of extracellular spaces, (iii) accumulation of storage material within cardiomyocytes, or (iv) endomyocardial fibrosis. Many disorders do not show restrictive pathophysiology throughout their natural history, but only at an initial stage (with an evolution towards a hypokinetic and dilated phenotype) or at a terminal stage (often progressing from a hypertrophic phenotype). Furthermore, elements of both hypertrophic and restrictive phenotypes may coexist in some patients, making the classification challenge. Restrictive pathophysiology can be demonstrated by cardiac catheterization or Doppler echocardiography. The specific conditions may usually be diagnosed based on clinical data, 12-lead electrocardiogram, echocardiography, nuclear medicine, or cardiovascular magnetic resonance, but further investigations may be needed, up to endomyocardial biopsy and genetic evaluation. The spectrum of therapies is also wide and heterogeneous, but disease-modifying treatments are available only for cardiac amyloidosis and, partially, for iron overload cardiomyopathy.

Over the last year, 5 national or international scientific societies have issued documents regarding cardiac amyloidosis (CA) to highlight the emerging clinical science, raise awareness, and facilitate diagnosis and management of CA. These documents provide useful guidance for clinicians managing patients with CA, and all include: 1) an algorithm to establish a diagnosis; 2) an emphasis on noninvasive diagnosis with the combined use of bone scintigraphy and the exclusion of a monoclonal protein; and 3) indications for novel disease-modifying therapies for symptomatic CA, either with or without peripheral neuropathy. Nonetheless, the documents diverge on specific details of diagnosis, risk stratification, and treatment. Highlighting the similarities and differences of the documents by the 5 scientific societies with respect to diagnosis, risk stratification, and treatment offers useful insight into the knowledge gaps and unmet needs in the management of CA. An analysis of these documents, therefore, highlights "gray zones" requiring further investigation.

In the last years, statistics show a growing trend of harmful events caused by adverse weather. This trend suggests a revision of power systems management criteria, with the aim of reducing the effects of faults and/or harmful conditions. For this purpose, the availability of additional information about the status of the power system can allow a significant improvement compared with the current standards. In particular, additional information concerning the mechanical state of the lines can allow automatic detection of some types of harmful events. This work proposes some algorithms for the automatic detection of some types of events on overhead lines (OHLs) of the 132 kV and 150 kV sub-transmission networks, as these voltage levels show the highest number of faults. As to the causes of faults, Italian data show that the long supply interruptions are mainly caused by contact with (fall of) trees, atmospheric events (lightening, wind, snow, ice), and conductors and components wear. The algorithms described in this work are based on the mechanical monitoring of OHLs and aim for the automatic detection of the following three types of events: conductor breaking, fall of trees on the line conductors, snow/ice accretion on the line conductors. In addition, the proposed approach would allow an approximate location of these events along the involved OHLs. Overall, automatic detection of the type of event and its location along a line can provide significant advantages concerning the operation and management of the power system. On the other hand, the mechanical monitoring of OHLs requires the installation of a limited number of additional sensors and a limited overall cost in comparison with the expected benefits.

We describe an efficient photocatalytic procedure for the direct iodosulfonylation of terminal olefins 3 with α-iodo phenylsulfones 4. Specifically, the process uses the simple, robust, and fully recyclable phenol derivative 6e as the precatalytic system and occurs with visible-light irradiation (450 nm). Mechanistic investigations proved the key role of the in situ generated photocatalyst, namely phenolate anion 7e, which has shown high catalytic activity and considerable stability toward the operating conditions. Importantly, this photocatalytic transformation provides a wide variety of densely functionalized alkyl iodides 5 (23 examples, up to 95% yield). Finally, the synthetic potential of this photochemical transformation was demonstrated by scaling up the process under microfluidic conditions (up to 0.67 mmol h–1) while accessing a series of relevant product manipulations.

This work demonstrates that accurate hear beat monitoring, via photoplethysmography (PPG), can be performed at micro-power consumption level with an ear worn device. This is achieved thanks to the combination of a highly sensitive low power PPG chip, an optimal optical module, and an ergonomic design of the wearable device. The monolithic optical sensor is fabricated in a 180nm CMOS image sensor (CIS) process and features an area of 1.5mm by 1.5mm only. It implements an array of pixels, newly designed for PPG, and reaching a quantum efficiency of 85% up to 800nm. The presented sensor consumes 60 $\mu \text{A}$ at 122Hz sampling frequency, including digital communication. The optical design optimization enables high signal-to-noise ratio (SNR) PPG signals with less than 10 $\mu \text{A}$ average LED current. Heart beat monitoring, using the presented wearable device, is performed on 7 subjects and compared with a medical electrocardiogram (ECG). The earbud device correctly detects 98.47% of the beats on a total of 72.21 hours of recordings. The inter-beat interval (IBI) estimation from these recordings features a mean absolute error (MAE) as low as 7.52ms.

Background The Orsiro cobalt-chromium stent platform (Biotronik, Bulach, Switzerland) is one of the first devices in the era of ultrathin struts. However, data regarding the efficacy of Orsiro stent in patients with challenging anatomical conditions obtained from daily clinical practice are scant. Methods We retrospectively reviewed the long-term outcomes, defined as target lesion revascularization (TLR), target vessel revascularization (TVR), stent thrombosis (ST) and cardiovascular (CV) mortality over a six years period, in 1161 consecutive patients (mean age 64.3 ± 11.2 years old, 681 males) treated with 2327 Orsiro stents in our institution who presented with challenging anatomic/angiographic features. Results The mean number of implanted stents was 1.7 ± 2.1 whereas the mean stent diameter and length were 3.6 ± 1.1 and 32.7 ± 15.6 mm, respectively. Mean follow-up duration was 35.6 ± 17 months (range 1–77 months); 923 patients (79.5%) reached the 3-year follow-up. The global rates of TLR, TVR, ST and CV mortality were 0.1%, 1.37%, 0.002%, and 1.9%, respectively with scarce statistically significant differences in multivessel disease, severe calcification, and lesion length > 41 mm. Multivariate regression analysis revealed that age, stent dislodgement , early stent thrombosis (p = 0.001) and lesion length ≥ 41 mm (p = 0.001) were independent predictors of TVR. Similarly, the occurrence of TLR was independently predicted by age, severe calcification, use of IVUS and Rotablator (p = 0.002), early stent thrombosis, LM bifurcation and length ≥ 41 mm (p = 0.001). Conclusions The Orsiro stent confirmed a very high efficacy profile in all anatomical scenarios with very low rates of clinically driven TLR and TVR, CV mortality and ST at 3-years.

The approval of new heart failure (HF) therapies has slowed over the past two decades in part due to the high costs of conducting large randomized clinical trials that are needed to adequately power major clinical endpoint studies. Several biomarkers have been identified reflecting different elements of HF pathophysiology, with possible applications in diagnosis, risk stratification, treatment monitoring, and even in the design of clinical trials. Biomarkers could potentially be used to refine study inclusion criteria to enable enrolment of patients who are more likely to respond to a therapeutic intervention, despite being at sufficient risk to meet predetermined study endpoint rates. When there is a close relationship between biomarker levels and clinical endpoints, changes in biomarker levels after a given treatment can act as a surrogate endpoint, potentially reducing the duration and cost of a clinical trial. Natriuretic peptides have been widely used in clinical trials with a variable amount of added value, which such variation being probably due to the absence of a close pathophysiological connection to the study drug. Notable exceptions to this include sacubitril/valsartan and vericiguat. Future studies should seek to adopt unbiased approaches for discovery of true companion diagnostics; with -omics-based tools, biomarkers might be more precisely selected for use in clinical trials to identify responses that closely reflect the biological effects of the drug under investigation. Finally, biomarkers associated with cardiac damage and remodelling, such as cardiac troponin, could be employed as safety endpoints provided that standardization between different assays is achieved.

Background: Electrocardiographic/echocardiographic abnormalities consistent with early-stage cardiomyopathy were previously reported in creatine transporter (CrT) deficiency. Nevertheless, cardiac involvement has never been accurately characterized. Aim: widen the current knowledge of the cardiac phenotype associated with creatine deficiency in a murine transgenic model and in patients with creatine deficiency syndrome (CDS). Methods: Wild type and transgenic CrT -/y mice (n=20) were serially evaluated in vivo by electrocardiogram (EKG) and echocardiography for 6 months, and ex vivo by histological/biochemical analyses. Nine patients with CDS (n=4 with L-arginine:glycine amidinotransferase - AGAT- deficiency, n=5 with CrT deficiency) underwent blood samples, including cardiac biomarkers, EKG, Holter monitoring, echocardiography and cardiac magnetic resonance (CMR). Results: Compared to wild type, CrT -/y mice showed a prolongation of QT interval (p=0.008) associated with a lower expression of ATPase sarcoplasmic/endoplasmic reticulum Ca 2+ transporting 2, involved in turn in intracellular Ca 2+ homeostasis. The significant reduction in mitochondrial ATP rate production (p Conclusion: Prolonged QT interval is observed in murine model - even with a slightly impaired metabolism - and in subjects with CrT deficiency. Biohumoral signs of neurohormonal activation and an initial replacement fibrosis - the latter suggested by the increase of native T1 - are identified in subjects with AGAT deficiency, but their clinical significance remains to be determined.

The approval of new heart failure (HF) therapies has slowed over the past two decades in part due to the high costs of conducting large randomized clinical trials that are needed to adequately power major clinical endpoint studies. Several biomarkers have been identified reflecting different elements of HF pathophysiology, with possible applications in diagnosis, risk stratification, treatment monitoring, and even in the design of clinical trials. Biomarkers could potentially be used to refine study inclusion criteria to enable enrolment of patients who are more likely to respond to a therapeutic intervention, despite being at sufficient risk to meet pre-determined study endpoint rates. When there is a close relationship between biomarker levels and clinical endpoints, changes in biomarker levels after a given treatment can act as a surrogate endpoint, potentially reducing the duration and cost of a clinical trial. Natriuretic peptides have been widely used in clinical trials with a variable amount of added value, which such variation being probably due to the absence of a close pathophysiological connection to the study drug. Notable exceptions to this include sacubitril/valsartan and vericiguat. Future studies should seek to adopt unbiased approaches for discovery of true companion diagnostics; with -omics-based tools, biomarkers might be more precisely selected for use in clinical trials to identify responses that closely reflect the biological effects of the drug under investigation. Finally, biomarkers associated with cardiac damage and remodelling, such as cardiac troponin, could be employed as safety endpoints provided that standardization between different assays is achieved. © 2022 European Society of Cardiology.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Objetivo: O presente estudo avaliou metabólitos circulantes no plasma de pacientes com e sem leiomiomas, buscando definir um perfil metabolômico de tais pacientes e compará-las metabolomicamente entre si, de acordo com a presença de leiomioma e o volume uterino. Métodos: Estudo observacional, transversal, incluindo mulheres divididas em três grupos: 37 com leiomiomas e útero acima de 500 cm3, 17 com leiomiomas e útero de até 150 cm3 e 21 mulheres sem leiomiomas. As pacientes foram submetidas à coleta de sangue periférico seguida de avaliação metabólica global por cromatografia gasosa acoplada a espectrômetro de massa. Resultados: Os três grupos de pacientes foram semelhantes estatisticamente no que diz respeito a características antropométricas e demográficas e exames laboratoriais. Encontramos diferenças estatísticas entre os grupos para o volume do útero (p

Maytenus ilicifolia or "Espinheira-Santa" is a renowned Brazilian medicinal plant usually used against intestinal and stomach ulcers. Other species with similar thorny leaves have raised great confusion in order to discern the authentic M. ilicifolia. Misidentifications can lead to product adulteration of authentic M. ilicifolia with other species, which can be found on the Brazilian market. The intake of misclassified herbal products potentially could be fatal, demanding faster reliable fingerprinting-based classification methods. In this study, the use of 1H HR-MAS NMR metabolomics fingerprinting and principal component analysis (PCA) allowed an evaluation of the authenticity for both collected and commercial M. ilicifolia samples, from the content of the flavanol, (-)-epicatechin (2), by observing variations in metabolic patterns. Plant specimen types from cultivated and natural habitats were analyzed by considering seasonal and topological differences. The interand intraplant topological metabolic profiles were found to be affected by seasonal and/or ecological trends such as sunlight, shade, rain, and the presence of pathogens. Moreover, several commercial samples, labeled as M. ilicifolia, were evaluated, but most of these products were of an inadequate quality.

Cardiac Magnetic Resonance (CMR) data regarding myocarditis presentation and disease course is still lacking in pediatric patients. We evaluate baseline CMR and evolution of functional and tissue abnormalities in children with acute myocarditis.CMR was performed in 125 patients with clinical diagnosis of acute myocarditis. Clinical follow-up was performed for a median of 498 (214-923) days.LVEF was depressed (55%) in 56 cases (45%) upon baseline CMR. LGE was found in 93 patients (77%) of cases. LGE was exclusively subepicardial in 29 patients (23%), while other LGE patterns (midwall/mixed) were present in 64 (51%). CMR was repeated in 92 (74%) patients. 67% presented recover of function at a median of 170 (70-746) days after onset of symptoms. Midwall/mixed LGE pattern had a statistically significant correlation with absent recover of function (OR 0.20 p 0.036). Thirteen patients (16%) had recovery from LV dysfunction but with persistence of LGE. Sub-epicardial pattern of LGE (OR 3.33, 95% CI 1.08-10.2, p = 0.036) and the presence of fever at admission (OR 4.67, 95% CI 1.16-18.7, p = 0.03) were associated with a significantly higher likelihood of complete normalization while midwall/mixed LGE pattern was associated with non-recovery.In pediatric myocarditis, midwall/mixed LGE pattern is associated with absent recover of function. Patients with recover of function may still have persistence of LGE, while a complete recovery from functional and tissue abnormalities is found only in a third of patients. Midwall/mixed pattern of LGE at first MRI was associated to worse outcome.