Application of a portable instrument for rapid and reliable detection of SARS-CoV-2 infection in any environment.

The ongoing outbreak of the novel coronavirus (SARS-CoV-2) infection is creating serious challenges for health laboratories that seek to identify viral infections as early as possible, optimally at the earliest appearance of symptom. Indeed, there is urgent need to develop and deploy robust diagnostic methodologies not only to use in health laboratory environments but also directly in places where humans circulate and spread the virus such as airports, trains, boats, and any public aggregation places. The success of a reliable and sensitive asymptomatic diagnosis relies on the identification and measurement of informative biomarkers from human host and virus in a rapid, sensitive, and inexpensive manner. The objective of this article is to describe an innovative multidisciplinary approach to develop an efficient, inexpensive, and easy-to-use portable instrument (bCUBE® by Hyris Ltd) that can be employed as a surveillance system for the emergency caused by SARS-CoV-2. A solution for Coronavirus testing, compliant with CDC guidelines, is scheduled to be released in the next weeks. In addition, we will describe a workflow and path of an integrated multi-omic approach that will lead to host and pathogen biomarker discovery in order to train the instrument to provide reliable results based on a specific biomarker's fingerprint of SARS-CoV-2 infection.

Subclinical Target Organ Damage in a Sample of Children with Autosomal Dominant Polycystic Kidney Disease: A Pilot Study.

Background and Objectives: Hypertension and vascular damage can begin in adolescents affected by Autosomal Dominant Polycystic Kidney Disease (ADPKD). This study aimed to evaluate markers of vascular damage and left ventricular geometry in a sample of children with ADPKD. Materials and Methods: Several vascular measurements were obtained: ambulatory blood pressure monitoring (ABPM), carotid intima-media thickness (cIMT), carotid distensibility coefficient (cDC), pulse wave velocity (PWV), and echocardiographic measurements (relative wall thickness (RWT) and left ventricular mass index (LVMI)). Results: Eleven ADPKD children were recruited (four females and seven males, mean age 9.5 ± 3.2 years). Four children were hypertensive at the ABPM, five were normotensive, and for two ABPM was not available. RWT was tendentially high (mean 0.47 ± 0.39). Eight patients had concentric cardiac remodeling, while one patient had cardiac hypertrophy. cIMT was above the 95° percentile for sex and height in 80% of the children (0.5 ± 0.005 mm). The average PWV and cDC were between the normal range (5.5 ± 4.6 m/s and 89.6 ± 16.1 × 10-3/KPa, respectively). We observed a positive correlation between the PWV and RWT (r = 0.616; p = 0.044) and a negative correlation between cDC and RWT (r = -0.770; p = 0.015). Cardiovascular damages (cIMT > 95° percentile) were found in normotensive patients. Conclusions: Increased RWT and high cIMT, indicating subclinical organ damage, are already present in ADPKD children. RWT was significantly correlated to that of cDC and PWV, implying that vascular stiffening is associated with cardiac remodeling. None of the children had an alteration in renal function. Subclinical cardiovascular damage preceded the decline in glomerular filtration rate.

Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia.

OBJECTIVE: Pulmonary thrombosis is observed in severe acute respiratory syndrome coronavirus 2 pneumonia. Aim was to investigate whether subpopulations of platelets were programmed to procoagulant and inflammatory activities in coronavirus disease 2019 (COVID-19) patients with pneumonia, without comorbidities predisposing to thromboembolism. Approach and Results: Overall, 37 patients and 28 healthy subjects were studied. Platelet-leukocyte aggregates, platelet-derived microvesicles, the expression of P-selectin, and active fibrinogen receptor on platelets were quantified by flow cytometry. The profile of 45 cytokines, chemokines, and growth factors released by platelets was defined by immunoassay. The contribution of platelets to coagulation factor activity was selectively measured. Numerous platelet-monocyte (mean±SE, 67.9±4.9%, n=17 versus 19.4±3.0%, n=22; P<0.0001) and platelet-granulocyte conjugates (34.2±4.04% versus 8.6±0.7%; P<0.0001) were detected in patients. Resting patient platelets had similar levels of P-selectin (10.9±2.6%, n=12) to collagen-activated control platelets (8.7±1.5%), which was not further increased by collagen activation on patient platelets (12.4±2.5%, P=nonsignificant). The agonist-stimulated expression of the active fibrinogen receptor was reduced by 60% in patients (P<0.0001 versus controls). Cytokines (IL [interleukin]-1α, IL-1ß, IL-1RA, IL-4, IL-10, IL-13, IL, 17, IL-27, IFN [interferon]-α, and IFN-γ), chemokines (MCP-1/CCL2 [monocyte chemoattractant protein 1]), and growth factors (VEGF [vascular endothelial growth factor]-A/D) were released in significantly larger amounts upon stimulation of COVID-19 platelets. Platelets contributed to increased fibrinogen, VWF (von Willebrand factor), and factor XII in COVID-19 patients. Patients (28.5±0.7 s, n=32), unlike controls (31.6±0.5 s, n=28; P<0.001), showed accelerated factor XII-dependent coagulation. CONCLUSIONS: Platelets in COVID-19 pneumonia are primed to spread proinflammatory and procoagulant activities in systemic circulation.

Beneficial effects of DAAs on cardiac function and structure in hepatitis C patients with low-moderate liver fibrosis.

Hepatitis C virus (HCV)-related chronic infection has been associated with a higher incidence of cardiovascular diseases. An altered morphology and function of both left and right heart have been described in HCV patients; however, the causality of the association is still debated. Ninety-eight nonobese and nondiabetic HCV patients (59.5 ± 12.0 years; males 52%) with Fibroscan-Transient Elastography assessed low-moderate liver fibrosis that achieved sustained viral response at 12 and 24 weeks after DAAs (direct-acting antivirals) participated. 56 were matched with 52 control subjects for age, sex and cardiovascular risk factors at baseline. A trans-thoracic echocardiography was performed in each subject at baseline (T0) and repeated in all HCV patients after eradication (6 months later eligibility, T1). TNF-α and IL-10 were measured at baseline and at T1. A concentric remodelling of the left heart in HCV participants was identified, whereas tricuspidal annular plane systolic excursion, right indexed atrial volume, right basal ventricular diameter, inferior vena cava diameter and pulmonary arterial pressure were higher in HCV participants compared to matched controls. After virus eradication, left indexed atrial volume and all right cardiac chambers measures were lower than baseline. A significant reduction of TNF-α was shown at T1, while IL-10 did not change. This study shows a concentric remodelling of the left ventricle and structural modifications in the right sections in HCV patients compared to controls. Virus eradication with DAAs was associated with a reduction of the main right atrioventricular parameters indicating a direct involvement of the HCV in cardiac changes.

The good bugs: the use of probiotics in pediatrics.

PURPOSE OF REVIEW: There is growing evidence encouraging the use of probiotics in many conditions in children. However, given the wide number of probiotics available and contradictory data in the literature, the health-care provider is often faced with uncertainness about whether or not to use probiotics and which one(s) to choose. We here review current hypotheses regarding the efficacy and safety of probiotics and evaluate the available data on the use of probiotics in most common diseases in children. Considering that probiotics have strain-specific effects, we will focus on individual probiotic strains rather than on probiotics in general. RECENT FINDINGS: Strain-specific efficacy was clearly demonstrated with Lactobacillus rhamnosus GG and Saccharomyces boulardii I-745 in the treatment of acute infectious diarrhea, Lactobacillus reuteri DSM 17938 in infantile colics, Lactobacillus rhamnosus GG, and VSL#3 in irritable bowel syndrome. In addition, encouraging results are seen for use of probiotics in necrotizing enterocolitis, food allergy, and nonalcoholic fatty liver disease. However, the data available for constipation are to be considered somewhat equivocal. SUMMARY: The clinical relevance of these findings indicates that healthcare providers need to take strain-specificity and disease specificity of probiotics into consideration when recommending probiotic for their patients.

Transvenous lead extraction procedures in women based on ESC-EHRA EORP European Lead Extraction ConTRolled ELECTRa registry: is female sex a predictor of complications?

AIMS: Female sex is considered an independent risk factor of transvenous leads extraction (TLE) procedure. The aim of the study was to evaluate the effectiveness of TLE in women compared with men. METHODS AND RESULTS: A post hoc analysis of risk factors and effectiveness of TLE in women and men included in the ESC-EHRA EORP ELECTRa registry was conducted. The rate of major complications was 1.96% in women vs. 0.71% in men; P = 0.0025. The number of leads was higher in men (mean 1.89 vs. 1.71; P < 0.0001) with higher number of abandoned leads in women (46.04% vs. 34.82%; P < 0.0001). Risk factors of TLE differed between the sexes, of which the major were: signs and symptoms of venous occlusion [odds ratio (OR) 3.730, confidence interval (CI) 1.401-9.934; P = 0.0084], cumulative leads dwell time (OR 1.044, CI 1.024-1.065; P < 0.001), number of generator replacements (OR 1.029, CI 1.005-1.054; P = 0.0184) in females and the number of leads (OR 6.053, CI 2.422-15.129; P = 0.0001), use of powered sheaths (OR 2.742, CI 1.404-5.355; P = 0.0031), and white blood cell count (OR 1.138, CI 1.069-1.212; P < 0.001) in males. Individual radiological and clinical success of TLE was 96.29% and 98.14% in women compared with 98.03% and 99.21% in men (P = 0.0046 and 0.0098). CONCLUSION: The efficacy of TLE was lower in females than males, with a higher rate of periprocedural major complications. The reasons for this difference are probably related to disparities in risk factors in women, including more pronounced leads adherence to the walls of the veins and myocardium. Lead management may be key to the effectiveness of TLE in females.

Left Ventricular Long-Axis Function Assessed with Cardiac Cine MR Imaging Is an Independent Predictor of All-Cause Mortality in Patients with Reduced Ejection Fraction: A Multicenter Study.

Purpose To evaluate the prognostic value of a simple index of left ventricular (LV) long-axis function-lateral mitral annular plane systolic excursion (MAPSE)-in a large multicenter population of patients with reduced ejection fraction (EF) who were undergoing cardiac magnetic resonance (MR) imaging. Materials and Methods This retrospective study included 1040 consecutive patients (mean age, 59.5 years ± 15.8) at four U.S. medical centers who were undergoing cardiac MR imaging for assessment of LV dysfunction with EF less than 50%. Lateral MAPSE was measured in the four-chamber cine view. The primary end point was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between lateral MAPSE and death. The incremental prognostic value of lateral MAPSE was assessed in nested models. Results During a median follow-up of 4.4 years, 132 patients died. With Kaplan-Meier analysis, the risk of death increased significantly with decreasing tertiles of lateral MAPSE (log-rank P = .0001). Patients with relatively preserved lateral MAPSE (>9 mm) had very few deaths, regardless of whether their EF was above or below 35%. Patients with late gadolinium enhancement (LGE) and low lateral MAPSE had significantly reduced survival compared to those with LGE and high lateral MAPSE (log-rank P < .0001). Lateral MAPSE was independently associated with risk of death after adjustment for clinical and imaging risk factors, which were univariate predictors (age, body mass index, diabetes, LV end-diastolic volume index, LGE, EF) (hazard ratio = 2.051 per mm decrease; 95% confidence interval [CI]: 1.520, 2.768; P < .001). Inclusion of lateral MAPSE in this model resulted in significant improvement in model fit (likelihood ratio test P < .0001) and C statistic (increasing from 0.675 to 0.844; P < .0001). Continuous net reclassification improvement was 1.036 (95% CI: 0.878, 1.194). Conclusion Lateral MAPSE measured during routine cine cardiac MR imaging is a significant independent predictor of mortality in patients with LV dysfunction, incremental to common clinical and cardiac MR risk factors-including EF and LGE. © RSNA, 2017.

The European Lead Extraction ConTRolled (ELECTRa) study: a European Heart Rhythm Association (EHRA) Registry of Transvenous Lead Extraction Outcomes.

AIMS: The European Lead Extraction ConTRolled Registry (ELECTRa), is a prospective registry of consecutive transvenous lead extraction (TLE) procedures conducted by the European Heart Rhythm Association (EHRA) in order to identify the safety and efficacy of the current practice of TLE. METHODS AND RESULTS: European centres performing TLE, invited by the organizing committee on behalf of EHRA, prospectively recruited all consecutive patients undergoing TLE at their institution. The primary endpoint was TLE safety defined by pre-discharge major procedure-related complications including death. Secondary endpoints included clinical and radiological success and overall complication rates. Outcomes were compared between Low Volume (LoV) vs. High Volume (HiV) centers (LoV < 30 and HiV ≥ 30 procedures/year). A total of 3555 consecutive patients (pts) of whom 3510 underwent TLE at 73 centres in 19 European countries were enrolled between November 2012 and May 2014. The primary endpoint of in-hospital procedure-related major complication rate was 1.7% [95% CI 1.3-2.1%] (58/3510 pts) including a mortality of 0.5% [95% CI 0.3-0.8%] (17/3510 pts). Approximately two-thirds (37/58) of these complications occurred during the procedure and one-third (21/58) in the post-operative period. The most common procedure related complications were those requiring pericardiocentesis or chest tube and/or surgical repair (1.4% [95% CI 1.0-1.8%]). Complete clinical and radiological success rates were 96.7% [95% CI 96.1-97.3%] and 95.7% [95% CI 95.2-96.2%], respectively. The all cause in-hospital major complications and deaths were significantly lower in HiV centres vs. LoV centres (2.4% [95% CI 1.9-3.0%] vs. 4.1% [95% CI 2.7-6.0%], P = 0.0146; and 1.2% [95% CI 0.8-1.6%] vs. 2.5% [95% CI 1.5-4.1%] P = 0.0088), although those related to the procedure did not reach statistical significance. Radiological and clinical successes were more frequent in HiV vs. LoV centres. CONCLUSION: The ELECTRa study is the largest prospective registry on TLE and confirmed the safety and efficacy of the current practice of TLE. Lead extraction was associated with a higher success rate with lower all cause complication and mortality rates in high volume compared with low volume centres.

Abdominal Pain-Associated Functional Gastrointestinal Disorder Prevalence in Children and Adolescents with Celiac Disease on Gluten-Free Diet: A Multinational Study.

OBJECTIVE: To test the hypothesis that children with celiac disease (CD) on gluten-free diet are at increased risk of abdominal pain (AP) associated-functional gastrointestinal disorders (FGIDs). STUDY DESIGN: This was a multinational cross-sectional study performed from 2014 to 2015. Patients 4-18 years of age with CD on gluten-free diet for longer than 6 months were recruited from pediatric CD clinics in US and Italy. Control groups included siblings of children with CD (with normal tissue transglutaminase levels) and unrelated controls. Subjects or parents completed the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III. RESULTS: Children (n = 289) were recruited (55% US, 45% Italy): 96 children with CD, 96 sibling controls, and 97 unrelated controls. Chronic AP was present in 30 (30.9%) subjects with CD, 22 (22.7%) sibling controls, and 21 (21.6%) unrelated controls (P = .26 patients with CD vs siblings; P = .18 patients with CD vs unrelated; P = .96 siblings vs unrelated). AP-FGIDs were present in 8 (8.2%) subjects with CD, 8 (8.2%) sibling controls, and 2 (2.1%) unrelated controls (P = 1.00 subjects with CD vs sibling controls; P = .06 subjects with CD vs unrelated controls; P = .06 sibling controls vs unrelated controls). CONCLUSION: This multinational study evaluated the prevalence of chronic abdominal pain and AP-FGIDs in the pediatric population with CD. We found that subjects with CD and controls have a similar prevalence of chronic AP and AP-FGIDs. This suggests that not all types of gastrointestinal inflammation result in AP-FGIDs in children.

Left Ventricular global longitudinal strain predicts heart failure readmission in acute decompensated heart failure.

BACKGROUND: The goal of this study was to determine if left ventricular (LV) global longitudinal strain (GLS) predicts heart failure (HF) readmission in patients with acute decompensated heart failure. METHODS AND RESULTS: Two hundred ninety one patients were enrolled at the time of admission for acute decompensated heart failure between January 2011 and September 2013. Left ventricle global longitudinal strain (LV GLS) by velocity vector imaging averaged from 2, 3 and 4-chamber views could be assessed in 204 out of 291 (70%) patients. Mean age was 63.8 ± 15.2 years, 42% of the patients were males and 78% were African American or Hispanic. Patients were followed until the first HF hospital readmission up to 44 months. Patients were grouped into quartiles on the basis of LV GLS. Kaplan-Meier curves showed significantly higher readmission rates in patients with worse LV GLS (log-rank p < 0.001). After adjusting for age, sex, history of ischemic heart disease, dementia, New York Heart Association class, LV ejection fraction, use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, systolic and diastolic blood pressure on admission and sodium level on admission, worse LV GLS was the strongest predictor of recurrent HF readmission (p < 0.001). The ejection fraction was predictive of readmission in univariate, but not in multivariate analysis. CONCLUSION: LV GLS is an independent predictor of HF readmission after acute decompensated heart failure with a higher risk of readmission in case of progressive worsening of LV GLS, independent of the ejection fraction.

Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain.

The enzymatic conversion of progesterone and testosterone by the enzyme 5alpha-reductase exerts a crucial role in the control of nervous function. The effects of finasteride in the brain, an inhibitor of this enzyme used for the treatment of human benign prostatic hyperplasia and androgenic alopecia, have been poorly explored. Therefore, the effects of a subchronic treatment with finasteride at low doses (3 mg/kg/day) and the consequences of its withdrawal on neuroactive steroid levels in plasma, cerebrospinal fluid and some brain regions as well as on the expression of classical and non-classical steroid receptors have been evaluated in male rats. After subchronic treatment (i.e., for 20 days) the following effects were detected: (i) depending on the compartment considered, alteration in the levels of neuroactive steroids, not only in 5alpha-reduced metabolites but also in its precursors and in neuroactive steroids from other steroidogenic pathways and (ii) an upregulation of the androgen receptor in the cerebral cortex and beta3 subunit of the GABA-A receptor in the cerebellum. One month after the last treatment (i.e., withdrawal period), some of these effects persisted (i.e., the upregulation of the androgen receptor in the cerebral cortex, an increase of dihydroprogesterone in the cerebellum, a decrease of dihydrotestosterone in plasma). Moreover, other changes in neuroactive steroid levels, steroid receptors (i.e., an upregulation of the estrogen receptor alpha and a downregulation of the estrogen receptor beta in the cerebral cortex) and GABA-A receptor subunits (i.e., a decrease of alpha 4 and beta 3 mRNA levels in the cerebral cortex) were detected. These findings suggest that finasteride treatment may have broad consequences for brain function.

Left ventricular long axis function assessed during cine-cardiovascular magnetic resonance is an independent predictor of adverse cardiac events.

BACKGROUND: Left ventricular pump function requires a complex interplay involving myocardial fibers orientated in the longitudinal, oblique and circumferential directions. Long axis dysfunction appears to be an early marker for a number of pathological states. We hypothesized that mitral annular plane systolic excursion (MAPSE) measured during cine-cardiovascular magnetic resonance (CMR) reflects changes in long axis function and may be an early marker for adverse cardiovascular outcomes. The aims of this study were therefore: 1) To assess the feasibility and reproducibility of MAPSE measurements during routine cine-CMR; and 2) To assess whether MAPSE, as a surrogate for long axis function, is a predictor of major adverse cardiovascular events (MACE). METHODS: Four hundred consecutive patients undergoing CMR were prospectively enrolled. MAPSE was measured in the 4-chamber cine view. Patients were prospectively followed for major adverse cardiac events (MACE) - death, non-fatal myocardial infarction, hospitalization for heart failure or unstable angina, and late revascularization. Cox proportional hazards regression modeling was used to identify factors independently associated with MACE. Net reclassification improvement (NRI) was calculated to assess whether addition of MAPSE resulted in improved risk reclassification of MACE. RESULTS: Seventy-two MACE occurred during a median follow-up of 14.5 months. By Kaplan-Meier analysis, patients with lateral MAPSE <1.11 cm (median) experienced significantly higher incidence of MACE than patients with a MAPSE ≥1.11 cm (p = 0.027). After adjustment for established clinical risk factors which were univariate predictors (age, diabetes, hypertension, NYHA class, LV mass), lateral MAPSE remained a significant independent predictor of MACE (HR = 4.384 per cm decrease or 1.344 per 2 mm decrease; p = 0.020). Incorporation of lateral MAPSE into this risk model resulted in a net reclassification improvement (NRI) of 0.18 (p = 0.006). CONCLUSIONS: Reduced long axis function assessed with lateral MAPSE during cine-CMR is an independent predictor of MACE.

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis is a chronic inflammatory disease affecting the central nervous system. As reported by clinical observations, variation in hormonal levels might alter disease susceptibility and progression. Specifically, decreased levels of testosterone in males are reported to be permissive for disease onset. Accordingly, testosterone seems to exert protective effects in experimental autoimmune encephalomyelitis (EAE). In this context, it is important to highlight that testosterone is further metabolized into 17ß-estradiol or dihydrotestosterone (DHT). In this study, we aimed to explore the protective effects of DHT treatment in EAE Dark Agouti rats (i.e. an experimental model showing a protracted relapsing EAE). Data obtained 45 days after EAE induction showed that DHT exerts a beneficial effect on clinical scores, coupled with decreased gliosis (i.e. glial fibrillary acidic protein and major histocompatibility complex of class II staining) and inflammation (i.e. translocator protein 18 kDa, interleukin-1ß, Toll-like receptor 4 and nuclear factor-κB expression) in the spinal cord. Moreover, parameters linked to oxidative stress and tissue damage, like thiobarbituric acid-reactive substance levels and Bcl-2-associated X protein expression, and to mitochondrial activity (i.e. content of mitochondrial DNA and proteins), were improved after DHT administration. This neuroactive steroid may be further metabolized into 3α- or 3ß-diol. However, assessment of the levels of these metabolites after DHT treatment seems to suggest that the protective effects observed here are due to DHT itself. Altogether, the present results indicate that DHT was effective in reducing the severity of chronic EAE and, consequently, may represent an interesting perspective for multiple sclerosis treatment.

Neuroactive steroid levels in plasma and cerebrospinal fluid of male multiple sclerosis patients.

Neuroactive steroid family includes molecules synthesized in peripheral glands (i.e., hormonal steroids) and directly in the nervous system (i.e., neurosteroids) which are key regulators of the nervous function. As already reported in clinical and experimental studies, neurodegenerative diseases affect the levels of neuroactive steroids. However, a careful analysis comparing the levels of these molecules in cerebrospinal fluid (CSF) and in plasma of multiple sclerosis (MS) patients is still missing. To this aim, the levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in CSF and plasma of male adults affected by Relapsing-Remitting MS and compared with those collected in control patients. An increase in pregnenolone and isopregnanolone levels associated with a decrease in progesterone metabolites, dihydroprogesterone, and tetrahydroprogesterone was observed in CSF of MS patients. Moreover, an increase of 5α-androstane-3α,17ß-diol and of 17ß-estradiol levels associated with a decrease of dihydrotestosterone also occurred. In plasma, an increase in pregnenolone, progesterone, and dihydrotestosterone and a decrease in dihydroprogesterone and tetrahydroprogesterone levels were reported. This study shows for the first time that the levels of several neuroactive steroids, and particularly those of progesterone and testosterone metabolites, are deeply affected in CSF of relapsing-remitting MS male patients. We here demonstrated that, the cerebrospinal fluid and plasma levels of several neuroactive steroids are modified in relapsing remitting multiple sclerosis male patients. Interestingly, we reported for the first time that, the levels of progesterone and testosterone metabolites are deeply affected in cerebrospinal fluid. These findings may have an important relevance in therapeutic and/or diagnostic field of multiple sclerosis.

Standard and New Echocardio Techniques, Such as Global Longitudinal Strain, to Monitor the Impact of Diets on Cardiovascular Diseases and Heart Function.

"The Seven Countries Study", published in 1984, was the first study to find a correlation between diet and mortality related to cardiovascular diseases (CVDs). Since then, many investigations have addressed the relationship between type of diet, or specific nutrients, and CVDs. Based on these findings, some traditional dietary models, such as the Mediterranean or Nordic diet, are recommended to prevent CVDs. Meanwhile, new diets have been proposed for optimal nutrition therapy, for example, the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean-DASH Intervention Diet for Neurodegenerative Delay (MIND). The main outcomes evaluated after implementing these dietary models are as follows: CVD-related death; the development of specific CVDs, such as myocardial infarction and hypertension; or biochemical parameters related to CVDs, i.e., non-HDL cholesterol, C-reactive protein (CPR) and homocysteine. However, the early impact of diet on heart functionality is less evaluated. Recently, the echographic measurement of left ventricle (LV) deformation by global longitudinal strain (GLS) has been introduced as a novel marker of clinical and subclinical cardiac dysfunction. This technology allows a subclinical evaluation of heart functionality since, differently from the traditional evaluation of left ventricle ejection fraction (LVEF), it is capable of detecting early myocardial dysfunction. In this review, we analyzed the available studies that correlate dietetic regimens to cardiovascular diseases, focusing on the relevance of LV strain to detect subclinical myocardial alteration related to diet. Evidence is presented that DASH and MIND can have a positive impact on heart functionality and that myocardial strain is useful for early detection of diet-related changes in cardiac function.

Implications of Myocardial Strain in Primary Mitral Regurgitation - A Cardiovascular Magnetic Resonance Study.

AIMS: Chronic primary mitral regurgitation (MR) results in progressive left ventricular (LV) remodeling. Abnormal myocardial deformation (strain) can be present despite preserved ejection fraction. Cardiovascular magnetic resonance (CMR) feature-tracking techniques allow assessment of global longitudinal strain (GLS) from routine cine-images. The aim of this study was to evaluate the prognostic value of CMR feature-tracking derived GLS in patients with primary MR. METHODS AND RESULTS: Consecutive patients undergoing CMR for chronic MR from January 2012 to June 2018 were enrolled. Patient with LV ejection fraction <50% were excluded. The composite primary outcome aiming to detect decompensation related to MR comprised of 1) referral for mitral surgery due to symptoms or LV systolic dysfunction or 2) cardiovascular death. The secondary outcome was all-cause death. A total of 422 patients were followed for a median of 2.7 years, the primary endpoint was met in 93 patients (34 patients reported symptoms at baseline). On multivariable analysis, GLS≥ -16.6% was associated with primary outcome (hazard ratio 1.90,p=0.01). In moderate MR cohort, patient with GLS≥ -16.6% had worse event-free survival while no significant different in mild or severe MR groups. GLS≥ -16.0% remained associated with all-cause death after adjusting for other covariates including the MR severity (hazard ratio 2.24,p=0.02). CONCLUSIONS: In primary MR patients with preserved systolic function, GLS was associated with our composite outcomes and all-cause death. GLS may serve as a marker of cardiac dysfunction in primary MR patients with preserved systolic function allowing identification of patients likely to decompensate during observation.

From cell phenotype to epigenetic mechanisms: new insights into regenerating myocardium.

The self-regenerating property of the adult myocardium is not a new discovery. Even though we could not confirm that the adult myocardium is a post-mitotic tissue, we should consider that its plasticity is extremely low. Studies are still in progress to decipher the mechanisms underlying the abovementioned potential fetal features of the adult heart. The modest results of several clinical trials based on the transplantation of millions of autologous stem cells into the dysfunctional heart have confirmed that the cross-talk of different signals, such as the microenvironment, promotes the regeneration of adult myocardium. Recent scientific evidence has revealed that cellular cross-talk does not depend on the action of a single cell phenotype. It is conceivable that the limited turnover of cardiomyocytes is ensured by the interplay of adult cardiac cells in response to environmental changes. The epigenetic state of a cell serves as a dynamic interface between the environment and phenotype. The epigenetic modulation of the adult cardiac cells by natural active compounds encourages further studies to improve myocardial plasticity. In this review, we will highlight the most relevant studies demonstrating the epigenetic modulation of myocardial regeneration without the use of stem cell transplantation.