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The coronavirus disease 2019 (COVID-19) pandemic seems to be at its end. During the first outbreak, alfa was the dominant variant, and in the two following years, delta was the dominant variant. Questions remain about the prevalence and severity of post-COVID syndrome (PCS). We compared the medium-term outcomes of a selected group of patients considered at high risk for PCS: hospitalized patients with severe COVID-19 infection who presented clinical evidence of the acute onset of venous thromboembolism. Weighted Cox regression was used to estimate the adjusted hazard ratios for the risk of early and medium-term complications and quality of life (QoL) in COVID-19 patients developing acute venous thrombo-embolism according to the period of admission to the hospital. The primary outcome was the modification of QoL at a median follow-up of 24 months in patients hospitalized for COVID-19. The secondary outcome was the modification of QoL related to COVID-19 severity. The absolute risk of mortality for hospitalized COVID-19 patients was higher during the first outbreak (risk difference, 19% [95% confidence interval [CI], 16–22%]). Patients with acute onset of thromboembolism during the first outbreak had increased mortality, hospital stay, and need for intensive care unit treatment (p < 0.01). In patients who suffered from severe COVID-19 infection and thromboembolism in the following 2 years, symptoms during follow-up were less common and milder (risk difference 45% [95% CI, 40–52%]. In total, 19 patients were alive at 24 months follow-up: 12 patients (63%) reported important physical symptoms and 10 patients (52%) relevant emotional/mental symptoms. All patients reported reduced QoL in comparison with the preinfection time; in 15 patients (79%), the reduced QoL limited significantly their social and work activities. All patients reported permanent worsening of QoL after discharge from the hospital. Comparing the three different February to April interval years (2020, 2021, and 2022), patients reported a somewhat worse perception of health condition in comparison with the preinfection time, respectively, in 100, 79, and 56% respectively. The findings of our study show reduced prevalence and severity of PCS in the last 2 years. Less virulent variants, herd immunity, and vaccination may played a significant role. [ABSTRACT FROM AUTHOR]

The aim is to provide healthcare professionals with a practical diagnostic and treatment framework for patients of all ages and, as an increasing number of patients have a known genetic basis for their disease, the guideline also considers the implications of a diagnosis for families and provides advice on reproduction and contraception. Keywords: Guidelines; Arrhythmia; Arrhythmogenic right ventricular cardiomyopathy; Cardiomyopathies; Diagnosis; Dilated cardiomyopathy; Genetics; Genetic counselling; Genetic testing; Hypertrophic cardiomyopathy; Implantable cardioverter defibrillator; Management; Multimodality imaging; Non-dilated left ventricular cardiomyopathy; Pregnancy; Restrictive cardiomyopathy; Risk stratification; Screening; Sports; Sudden cardiac death EN Guidelines Arrhythmia Arrhythmogenic right ventricular cardiomyopathy Cardiomyopathies Diagnosis Dilated cardiomyopathy Genetics Genetic counselling Genetic testing Hypertrophic cardiomyopathy Implantable cardioverter defibrillator Management Multimodality imaging Non-dilated left ventricular cardiomyopathy Pregnancy Restrictive cardiomyopathy Risk stratification Screening Sports Sudden cardiac death 3503 3626 124 10/04/23 20231001 NES 231001 Table of contents 1. ESC Guidelines do not override the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient or the patient's caregiver where appropriate and/or necessary. The NDLVC phenotype will include individuals that up until now may have variably been described as having DCM (but without LV dilatation), arrhythmogenic left ventricular cardiomyopathy (ALVC), left-dominant ARVC, or arrhythmogenic DCM (but often without fulfilling diagnostic criteria for ARVC) ( I Figure 3 i ). [Extracted from the article]

Aims The aim of this study was to assess the morphological characteristics and prognostic implications of the optical coherence tomography (OCT)-derived lipid core burden index (LCBI). Methods and results OCT-LCBI was assessed in 1003 patients with 1-year follow-up from the CLIMA multicentre registry using a validated software able to automatically obtain a maximum OCT-LCBI in 4 mm (maxOCT-LCBI4mm). Primary composite clinical endpoint included cardiac death, myocardial infarction, and target-vessel revascularization. A secondary analysis using clinical outcomes of CLIMA study was performed. Patients with a maxOCT-LCBI4mm ≥ 400 showed higher prevalence of fibrous cap thickness (FCT) <75 μm [odds ratio (OR) 1.43, 95% confidence interval (CI) 1.03–1.99; P = 0.034], lipid pool arc >180° (OR 3.93, 95%CI 2.97–5.21; P < 0.001), minimum lumen area <3.5 mm2 (OR 1.5, 95%CI 1.16–1.94; P = 0.002), macrophage infiltration (OR 2.38, 95%CI 1.81–3.13; P < 0.001), and intra-plaque intimal vasculature (OR 1.34, 95%CI 1.05–1.72; P = 0.021). A maxOCT-LCBI4mm ≥400 predicted the primary endpoint [adjusted hazard ratio (HR) 1.86, 95%CI 1.1–3.2; P = 0.019] as well as the CLIMA endpoint (HR 2.56, 95%CI 1.24–5.29; P = 0.011). Patients with high lipid content and thin FCT < 75 µm were at higher risk for adverse events (HR 4.88, 95%CI 2.44–9.72; P < 0.001). Conclusions A high maxOCT-LCBI4mm was related to poor outcome and vulnerable plaque features. This study represents a step further in the automated assessment of the coronary plaque risk profile. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the different impact of optical coherence tomography (OCT)-derived vulnerable plaque features on future adverse events (AEs) according to the biological sex. Methods: The prospective multicenter CLIMA study (ClinicalTrials.gov: NCT02883088) enrolled 1003 patients with OCT plaque analysis of non-treated coronary plaques located in the proximal left anterior descending artery. Sex-specific differences in plaque composition and vulnerable features were described. We investigated the incidence of AEs, including cardiac death, any myocardial infarction and target vessel revascularization at 1-year. Results: Among 1003 patients, 24.6% were women. Women were older and more frequently affected by chronic kidney disease. Dyslipidemia, prior MI and smoking habit were more common in men. At OCT analysis, women had shorter plaque length (p < 0.001), ticker fibrous cap (p = 0.001), smaller maximum lipid arc (p = 0.019), lower macrophage infiltration (p < 0.001) and intra-plaque layered tissue (p = 0.007). During follow-up, 65 AEs were registered. The presence of a thin fibrous cap and a large macrophage infiltration (> 67°) predicted AEs in both sexes. The presence of macrophages (HR 3.38, p = 0.018) and a small minimum lumen area (HR 4.97, p = 0.002) were associated with AEs in women but not in men, while a large lipid arc (> 180°) was associated with AEs in men (HR 2.56, p = 0.003) but not in women. Conclusion: This subanalysis of the CLIMA study investigated for the first-time sex-specific OCT features of plaque vulnerability associated with AEs. Local inflammation was associated with AEs in women and a large lipid arc was predictive in men. OCT may help develop sex-specific risk stratification strategies. [ABSTRACT FROM AUTHOR]

lncRNAs are at the core of many regulatory processes and have also been recognized to be involved in various complex diseases. They affect gene regulation through direct interactions with RNA, DNA or proteins. Accordingly, lncRNA structure is likely to be essential for their regulatory function. Point mutations, which manifest as SNPs (single nucleotide polymorphisms) in genome screens, can substantially alter their function and, subsequently, the expression of their downstream regulated genes. To test the effect of SNPs on structure, we investigated lncRNAs associated with dilated cardiomyopathy. Among 322 human candidate lncRNAs, we demonstrate first the significant association of an SNP located in lncRNA H19 using data from 1084 diseased and 751 control patients. H19 is generally highly expressed in the heart, with a complex expression pattern during heart development. Next, we used MFE (minimum free energy) folding to demonstrate a significant refolding in the secondary structure of this 861 nt long lncRNA. Since MFE folding may overlook the importance of sub-optimal structures, we showed that this refolding also manifests in the overall Boltzmann structure ensemble. There, the composition of structures is tremendously affected in their thermodynamic probabilities through the genetic variant. Finally, we confirmed these results experimentally, using SHAPE-Seq, corroborating that SNPs affecting such structures may explain hidden genetic variance not accounted for through genome wide association studies. Our results suggest that structural changes in lncRNAs, and lncRNA H19 in particular, affect regulatory processes and represent optimal targets for further in-depth studies probing their molecular interactions. [ABSTRACT FROM AUTHOR]

Risk-reducing surgery (RRS) is recommended in BRCA-mutated carriers because of their increased risk of developing ovarian cancer, while its role is still discussed for women harboring mutations in non-BRCA homologous repair genes. The aim of this study was to retrospectively evaluate the occurrence of pathological findings in a high-risk population undergoing RRS in San Matteo Hospital, Pavia between 2012 and 2022, and correlate their genetic and clinical outcomes, comparing them with a control group. The final cohort of 190 patients included 85 BRCA1, 63 BRCA2, 11 CHEK2, 7 PALB2, 4 ATM, 1 ERCC5, 1 RAD51C, 1 CDH1, 1 MEN1, 1 MLH1 gene mutation carriers and 15 patients with no known mutation but with strong familial risk. Occult invasive serous carcinoma (HGSC) and serous tubal intraepithelial carcinoma (STIC) were diagnosed in 12 (6.3%) women, all of them BRCA carriers. No neoplastic lesion was diagnosed in the non-BRCA group, in women with familial risk, or in the control group. Oral contraceptive use and age ≤45 at surgery were both found to be favorable factors. While p53 signature and serous tubal intraepithelial lesion (STIL) were also seen in the control group and in non-BRCA carriers, STIC and HGSC were only found in BRCA1/2 mutation carriers. [ABSTRACT FROM AUTHOR]

The present investigation aims to study the interaction between systemic and intra-plaque inflammation in predicting cardiac events. We investigated C-reactive protein (CRP) levels as well as plaque inflammation with optical coherence tomography (OCT)-detected macrophages in the CLIMA study. 689 patients had admission CRP serum values reported, and high CRP values were defined as ≥ 2 mg/dl. The main study endpoint was a composite of cardiac death, myocardial infarction, and/or target vessel revascularization at 1-year follow-up. At multivariate Cox regression analysis, a large (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.2–4.3; p = 0.013) and superficial (HR 2.78, 95%CI 1.5–5.1; p = 0.001) macrophage arc was predicted of the main composite endpoint in patients with high CRP levels. Patients with large/superficial macrophage accumulation and low CRP levels were not at higher risk of adverse events. The presence of high CRP levels and large/superficial macrophage accumulation at OCT analysis identified patients at higher risk of clinical events. [ABSTRACT FROM AUTHOR]

The efficacy of pre-emptive therapy in the prevention of cytomegalovirus (CMV) disease and the potential association of CMV infection with the occurrence of chronic lung allograft dysfunction (CLAD) was evaluated in 129 lung transplant recipients receiving pre-emptive therapy based on pp65-antigenemia or CMV-DNA in the blood and in the bronchoalveolar lavage. Seventy-one (55%) patients received pre-emptive ganciclovir/valganciclovir (GCV/VGCV) for CMV infection for a median of 28 (9–191) days. Possible CMV disease occurred in six (5%) patients and was healed after the GCV/VGCV therapy. The cumulative incidence of CLAD was 38% and 54% at 5 and 10 years. Acute rejection and CMV load in the blood (but not in the lung) were independent predictors of the occurrence of CLAD. Pre-emptive therapy is highly effective in preventing CMV disease in lung recipients and does not induce a superior incidence of CLAD compared to what reported for other cohorts of patients who received an extended antiviral prophylaxis. [ABSTRACT FROM AUTHOR]

Pulmonary veno‐occlusive disease (PVOD) is a rare disease. It may be idiopathic or associated, in particular, with connective tissue disease, or it may develop after radiation exposure; in heritable forms of PVOD, the inheritance is autosomal recessive due to the presence of homozygous or compound heterozygous pathogenic variants in the EIF2AK4 gene. We describe the case of a young man whose PVOD was initially misdiagnosed as chronic thromboembolic pulmonary hypertension despite worsening after riociguat, nonspecific computed tomography pulmonary angiogram findings, and parental consanguinity could suggest an autosomal recessive disease. The correct diagnosis and the correct treatment are crucial given the high mortality rate of this disease. [ABSTRACT FROM AUTHOR]

Tacrolimus (TAC) is an immunosuppressant drug approved both in the US and in the EU, widely used for the prophylaxis of organ rejection after transplantation. This is a critical dose drug: low levels in whole blood can lead to low exposure and a high risk of acute rejection, whereas overexposure puts patients at risk for toxicity and infection. Both situations can occur at whole-blood concentrations considered to be within the narrow TAC therapeutic range. We assumed a poor correlation between TAC trough concentrations in whole blood and the incidence of acute rejection; therefore, we propose to study TAC concentrations in endomyocardial biopsies (EMBs). We analyzed 70 EMBs from 18 transplant recipients at five scheduled follow-up visits during the first year post-transplant when closer TAC monitoring is mandatory. We observed five episodes of acute rejection (grade 2R) in three patients (2 episodes at 0.5 months, 2 at 3 months, and 1 at 12 months), when TAC concentrations in EMBs were low (63; 62; 59; 31; 44 pg/mg, respectively), whereas concentrations in whole blood were correct. Our results are preliminary and further studies are needed to confirm the importance of this new strategy to prevent acute rejection episodes. [ABSTRACT FROM AUTHOR]

This document describes the contribution of clinical criteria to the interpretation of genetic variants using heritable Mendelian cardiomyopathies as an example. The aim is to assist cardiologists in defining the clinical contribution to a genetic diagnosis and the interpretation of molecular genetic reports. The identification of a genetic variant of unknown or uncertain significance is a limitation of genetic testing, but current guidelines for the interpretation of genetic variants include essential contributions from clinical family screening that can establish a de novo assignment of the variant or its segregation with the phenotype in the family. A partnership between clinicians and patients helps to solve major uncertainties and provides reliable and clinically actionable information. [ABSTRACT FROM AUTHOR]

Purpose: Near infrared spectroscopy-Intravascular ultrasound (NIRS-IVUS) provide a fully automated Lipid Core Burden Index (LCBI). Optical coherence tomography (OCT) is potentially capable of measuring lipid longitudinal extension in a dedicated two-dimensional LCBI spread-out plot. The present study has been designed to validate an automated approach to assess OCT images, able of providing a dedicated LCBI spread-out plot.Methods: We compared results obtained with conventional (manual) OCT, with those obtained with a novel automated OCT algorithm and with NIRS-IVUS in consecutive 40 patients. Our goal was to calculate the lipid core longitudinal extension in a dedicated two-dimensional LCBI spread-out plot. Three groups were identified according to the studied lesions: (1) culprit lesions in ACS patients (n = 16), (2) non-culprit lesions in ACS patients (n = 12) and (3) lesions in stable patients (n = 12). OCT (either manual and automated) and NIRS-IVUS assessment showed for culprit ACS plaques a more complex anatomy.Results: A strong trend for increased LCBI was found in the culprit ACS group, regardless of the adopted imaging modality (either NIRS-IVUS or automated OCT). A fair correlation was obtained for the maximum 4 mm LCBI measured by NIRS-IVUS and automated OCT (r = 0.75). The sensitivity and specificity of automated OCT to detect significant LCBI (> 400) were 90.5 and 84.2 respectively.Conclusion: We developed an OCT automated approach that can provide a dedicated lipid plaque spread-out plot to address plaque vulnerability. The automated OCT software can promote and improve OCT clinical applications for the identification of patients at risk of hard events. [ABSTRACT FROM AUTHOR]

lncRNAs are at the core of many regulatory processes and have also been recognized to be involved in various complex diseases. They affect gene regulation through direct interactions with RNA, DNA or proteins. Accordingly, lncRNA structure is likely to be essential for their regulatory function. Point mutations, which manifest as SNPs (single nucleotide polymorphisms) in genome screens, can substantially alter their function and, subsequently, the expression of their downstream regulated genes. To test the effect of SNPs on structure, we investigated lncRNAs associated with dilated cardiomyopathy. Among 322 human candidate lncRNAs, we demonstrate first the significant association of an SNP located in lncRNA H19 using data from 1084 diseased and 751 control patients. H19 is generally highly expressed in the heart, with a complex expression pattern during heart development. Next, we used MFE (minimum free energy) folding to demonstrate a significant refolding in the secondary structure of this 861 nt long lncRNA. Since MFE folding may overlook the importance of sub-optimal structures, we showed that this refolding also manifests in the overall Boltzmann structure ensemble. There, the composition of structures is tremendously affected in their thermodynamic probabilities through the genetic variant. Finally, we confirmed these results experimentally, using SHAPE-Seq, corroborating that SNPs affecting such structures may explain hidden genetic variance not accounted for through genome wide association studies. Our results suggest that structural changes in lncRNAs, and lncRNA H19 in particular, affect regulatory processes and represent optimal targets for further in-depth studies probing their molecular interactions. [ABSTRACT FROM AUTHOR]

Aims  Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure. Methods and results  We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P  = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P  = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication steps, respectively), while confirming two previously identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A genetic risk score constructed from the number of risk alleles at these four DCM loci revealed a 3-fold increased risk of DCM for individuals with 8 risk alleles compared to individuals with 5 risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analyses on iPSC-derived cardiomyocytes identify SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggest SMARCB1 as the candidate culprit gene. Conclusion  This study provides a better understanding of the genetic architecture of DCM and sheds light on novel biological pathways underlying heart failure. [ABSTRACT FROM AUTHOR]

Niemann-Pick Disease type B (NPDB) is a rare autosomal recessive disease belonging to the family of lysosomal storage disorders. NPDB is caused by mutations of sphingomyelin phosphodiesterase 1 gene (SMPD1) and is characterized by hepatosplenomegaly, interstitial lung disease, recurrent pulmonary infections, and neurologic disorders. Bronchiectasis are atypical. Until now, only three cases of lung transplantation for severe respiratory impairment have been reported. We describe a case of NPDB that was diagnosed after lung transplantation for cystic bronchiectasis. In 2016, a 31-year-old woman who was experiencing hypoxemic respiratory failure and recurrent pulmonary infections due to cystic bronchiectasis received a double-lung-transplantation. Histopathologic study on removed lungs revealed clusters of CD68 foamy lipid-laden macrophages with concentric and palisade arrangement, compatible with the diagnosis of NPDB, which was confirmed after SMPD1 genetic sequencing. Twenty-three months after transplantation, allograft function is stable (FEV1 was 100% of best-FEV1). The singularity of this case lies in the presence of bronchiectasis, which is an unprecedently described phenotype of NPDB. This finding was accompanied by the detection of a novel SMPD1 mutation (p.Ala46=) of uncertain meaning. [ABSTRACT FROM AUTHOR]

lncRNAs are at the core of many regulatory processes and have also been recognized to be involved in various complex diseases. They affect gene regulation through direct interactions with RNA, DNA or proteins. Accordingly, lncRNA structure is likely to be essential for their regulatory function. Point mutations, which manifest as SNPs (single nucleotide polymorphisms) in genome screens, can substantially alter their function and, subsequently, the expression of their downstream regulated genes. To test the effect of SNPs on structure, we investigated lncRNAs associated with dilated cardiomyopathy. Among 322 human candidate lncRNAs, we demonstrate first the significant association of an SNP located in lncRNA H19 using data from 1084 diseased and 751 control patients. H19 is generally highly expressed in the heart, with a complex expression pattern during heart development. Next, we used MFE (minimum free energy) folding to demonstrate a significant refolding in the secondary structure of this 861 nt long lncRNA. Since MFE folding may overlook the importance of sub-optimal structures, we showed that this refolding also manifests in the overall Boltzmann structure ensemble. There, the composition of structures is tremendously affected in their thermodynamic probabilities through the genetic variant. Finally, we confirmed these results experimentally, using SHAPE-Seq, corroborating that SNPs affecting such structures may explain hidden genetic variance not accounted for through genome wide association studies. Our results suggest that structural changes in lncRNAs, and lncRNA H19 in particular, affect regulatory processes and represent optimal targets for further in-depth studies probing their molecular interactions. [ABSTRACT FROM AUTHOR]

Containment measures have been applied in several countries in order to limit the diffusion of the SARS-CoV-2 epidemic. The scope of this study is to analyze the evolution of the first wave of the SARS-CoV-2 epidemic throughout Italy and factors associated to the different way it spread in the Italian Regions, starting from the day that the first indigenous cases were detected through day 81 (6 days after the end of the strict lockdown). Data were obtained from daily reports and are represented as number (and percentage) of cases/100,000 persons. A lockdown with movement restrictions, especially across Regions, was declared at day 20. At day 81, 219,070 cases (363/100,000 persons) were diagnosed. A regression analysis based on the Gompertz model predicts a total number 233,606 cases (386/100,000 persons) at the end of the epidemic. The 21 areas, divided into Italian Regions and autonomous Provinces, showed a wide range in the frequency of cases at day 81 (58–921, median 258/100,000 persons) and total predicted cases (58–946, median 267/100,000 persons). Similarly, the predicted time for the end of the wave of the epidemic (considering as surrogate marker the time at which 99% of the total cases are predicted to occur) was highly variable, ranging from 64 to 136 (median 99) days. We analyzed the impact of local and interventional variables on the epidemic curve in each Region. The number of cases correlated inversely with the distance from the area in which first cases were detected and directly also with the gross domestic product pro capite (as a marker of industrial activity) of the Region. Moreover, an earlier start of the lockdown (i.e. in the presence of a lower number of cases) and wider testing were associated with a lower final number of total cases. In conclusion, this analysis shows that population-wide testing and early lockdown enforcement appear effective in limiting the spreading of the SARS-CoV-2 epidemic. [ABSTRACT FROM AUTHOR]

Surgical mortality is the most significant measure of outcome in surgical healthcare. The objective was to assess surgical 30 days mortality and improve the identification of predictors for personalized risk stratification of patients undergoing elective and emergency surgery. The study was conducted as a single-center cohort retrospective observational study, based on the analysis of data collected from patients surgically treated from 2002 to 2014 in a multi-disciplinary research and care referral hospital with global case mix of 1.27. The overall in-hospital mortality rate was 1.89% (95% CI 1.82–1.95). In the univariable analysis, numerous predictors were significantly associated with in-hospital death following surgery. In the multivariable model, age, BMI (Body Mass Index), ASA score, department, planned surgical complexity, surgical priority, previous surgeries in the same hospitalization, cardiovascular, pulmonary, hepato-renal comorbidities, drug intolerance, cancer and AIDS were independently associated with mortality after surgery. At logistic regression, the computed SMATT score (graded 0–100), generated on the basis of multivariate analysis, demonstrated a good discrimination (10-fold cross-validated AUC-ROC 0.945, 95%CI 0.941–0.948) and correctly classified 98.5% of those admissions with a probability of death >50%. The novel SMATT score, based on individual preoperative and surgical factors, accurately predicts mortality and provides dynamic information of the risk in redo/reoperative surgery. [ABSTRACT FROM AUTHOR]

In both classic and late-onset AFD, mutations of the GLA gene cause deficient activity of the alpha-galactosidase enzyme resulting in intracellular accumulation of the undigested substrate. Gastrointestinal symptoms (GI) are common but non-specific and imputed to the AFD, irrespective of the demonstration of substrate accumulation in GI cells. We demonstrate substrate accumulation in gastric epithelial, vascular, and nerve cells of patients with classic AFD and, vice versa, absence of accumulation in late-onset AFD and controls. [ABSTRACT FROM AUTHOR]

We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a 69-year-old patient with flu-like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock. The patient was successfully treated with venous-arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation. Cardiac function fully recovered in 5 days and ECMO was removed. Endomyocardial biopsy demonstrated low-grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung. [ABSTRACT FROM AUTHOR]

Objectives: N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM.Methods: We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion.Results: Of 357 patients enrolled, the median age was 52 (IQR: 36-65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10-4) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1-2 vs 3-4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001).Conclusions: MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM. [ABSTRACT FROM AUTHOR]

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and ∼10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies. [ABSTRACT FROM AUTHOR]

Introduction. In selected patients, the absorbable fibrin patch TachoSil® is superior to standard surgical treatment in reducing air leakage after pulmonary lobectomy. Pulmonary involvement is not considered a main feature of Marfan syndrome (MFS); however, spontaneous pneumothorax (SP) with a high rate of recurrence is frequently reported. We describe the use of TachoSil® in the supportive treatment of recurrent pneumothorax in a girl with MFS. Case Report. A 12-year-old girl with a previous diagnosis of MFS and recurrent history of left spontaneous pneumothorax was submitted to thoracoscopic atypical lung resection. Two patches (9.5 × 4.8 cm) were cut from the adhesive/foam complex (TachoSil®) and were pressed against the sutured area as supportive treatment. The patient recovered with no further SP recurrences. Conclusions. The use of the TachoSil® surgical patch may be useful in pneumothorax supportive treatment, particularly in pediatric MFS by ameliorating the mechanical strength of the lung. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) frequently affects relatively young, economically, and socially active adults, and is an important cause of heart failure and transplantation. DCM is a complex disease and its pathological architecture encounters many genetic determinants interacting with environmental factors. The old perspective that every pathogenic gene mutation would lead to a diseased heart, is now being replaced by the novel observation that the phenotype depends not only on the penetrance—malignancy of the mutated gene—but also on epigenetics, age, toxic factors, pregnancy, and a diversity of acquired diseases. This review discusses how gene mutations will result in mutation-specific molecular alterations in the heart including increased mitochondrial oxidation (sarcomeric gene e.g. TTN), decreased calcium sensitivity (sarcomeric genes), fibrosis (e.g. LMNA and TTN), or inflammation. Therefore, getting a complete picture of the DCM patient will include genomic data, molecular assessment by preference from cardiac samples, stratification according to co-morbidities, and phenotypic description. Those data will help to better guide the heart failure and anti-arrhythmic treatment, predict response to therapy, develop novel siRNA-based gene silencing for malignant gene mutations, or intervene with mutation-specific altered gene pathways in the heart. This article is part of the Mini Review Series from the Varenna 2017 meeting of the Working Group of Myocardial Function of the European Society of Cardiology. [ABSTRACT FROM AUTHOR]

Lamins A and C are intermediate filament nuclear envelope proteins encoded by the LMNA gene. Mutations in LMNA cause autosomal dominant severe heart disease, accounting for 10% of dilated cardiomyopathy (DCM). Characterised by progressive conduction system disease, arrhythmia and systolic impairment, lamin A/C heart disease is more malignant than other common DCMs due to high event rates even when the left ventricular impairment is mild. It has several phenotypic mimics, but overall it is likely to be an under-recognised cause of DCM. In certain clinical scenarios, particularly familial DCM with early conduction disease, the pretest probability of finding an LMNA mutation may be quite high.Recognising lamin A/C heart disease is important because implantable cardioverter defibrillators need to be implanted early. Promising oral drug therapies are within reach thanks to research into the mitogen-activated protein kinase (MAPK) and affiliated pathways. Personalised heart failure therapy may soon become feasible for LMNA, alongside personalised risk stratification, as variant-related differences in phenotype severity and clinical course are being steadily elucidated.Genotyping and family screening are clinically important both to confirm and to exclude LMNA mutations, but it is the three-pronged integration of such genetic information with functional data from in vivo cardiomyocyte mechanics, and pathological data from microscopy of the nuclear envelope, that is properly reshaping our LMNA knowledge base, one variant at a time. This review explains the biology of lamin A/C heart disease (genetics, structure and function of lamins), clinical presentation (diagnostic pointers, electrocardiographic and imaging features), aspects of screening and management, including current uncertainties, and future directions. [ABSTRACT FROM AUTHOR]

The article explores on the efficacy and safety of the implantable cardioverter-defibrillator (ICD) in reducing sudden cardiac death (SCD) in patients with non-ischemic dilated cardiomyopathy (DCM). It examines the medical protocols of symptomatic heart failure (HF). It also cites the assessment of ventricular fibrosis in the emergence of arrhythmogenic triggers in DCM patients.

A retrospective analysis of 3954 patients in phase 2/3 trials of bortezomib for treatment of multiple myeloma: towards providing a benchmark for cardiac safety profile of proteasome inhibition in multiple myeloma. Bortezomib is associated with a low risk of HF (around 4% of treated patient) [[3]] and retrospective analysis of patients with MM showed a low incidence of severe cardiac events in bortezomib-treated suggesting good cardiac tolerability. [Extracted from the article]

Background: Chronic viral infections of the heart are considered one antecedent event leading to progressive dysfunction of the myocardium, often with an impaired prognosis due to a virus- or immune-mediated myocardial injury. Symptomatic treatment does not influence the viral cause of heart failure, and the effect of antiviral treatment has not been determined, yet. Methods and results: In this phase II study 143 patients with symptoms of heart failure and biopsy-based confirmation of the enterovirus (EV), adenovirus, and/or parvovirus B19 genomes in their myocardial tissue were randomly assigned to double-blind treatment, and received either placebo ( n = 48) or 4 × 10 ( n = 49) and 8 × 10 IU ( n = 46) interferon beta-1b (IFN-β-1b) for 24 weeks, in addition to standard heart failure treatment. Patients with active myocarditis or other specific causes of heart failure were excluded. Compared to placebo, virus elimination and/or virus load reduction was higher in the IFN-β-1b groups (odds ratio 2.33, p = 0.048), similarly in both interferon groups and both strata. IFN-β-1b treatment was associated with favourable effects on NYHA functional class ( p = 0.013 at follow-up week 12), improvement in quality of life (Minnesota Heart Failure score; p = 0.032 at follow-up week 24) and patient global assessment (follow-up week 12 to follow-up week 24; p = 0.039). The frequency of adverse cardiac events was not higher in the IFN-β-1b groups compared to the placebo group. Conclusions: Immunomodulatory IFN-β-1b treatment is a well-tolerated and safe treatment option, leading to effective virus clearance or reduction of the virus load in patients with chronic viral cardiomyopathy. Favourable clinical effects assess quality of life, NYHA functional class, and patient global assessment. ClinicalTrials.gov identifier: NCT001185250 [ABSTRACT FROM AUTHOR]

In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where etiology directed management has great clinical relevance. [ABSTRACT FROM AUTHOR]

Background: The etiologic determinants of stroke in young adults remain a diagnostic challenge in up to one-fourth of cases. Increasing evidences led to consider Fabry's disease (FD) as a possible cause to check up. We aimed at evaluating the prevalence of unrecognized FD in a cohort of patients with juvenile stroke in northern Sardinia.Methods: For this study, we enrolled 178 patients consecutively admitted to our Neurological Ward for ischemic stroke, transient ischemic attack, intracerebral haemorrhage, neuroradiological evidence of silent infarcts, or white matter lesions possibly related to cerebral vasculopathy at brain MRI, and cerebral venous thrombosis. The qualifying events have to occur between 18 and 55 years of age.Results: We identified two patients with an α-galactosidase A gene variant, with a prevalence of 0.9 %. According to recent diagnostic criteria, one patient, included for the occurrence of multiple white matter lesions at brain MRI, had a diagnosis of definite FD, the other, included for ischemic stroke, had a diagnosis of uncertain FD.Conclusions: Our study places in a middle position among studies that found a prevalence of FD up to 4 % and others that did not find any FD patients. Our findings confirm that FD should be considered in the differential diagnosis of patients with juvenile stroke, particularly those with a personal or familial history positive for cerebrovascular events, or evidence of combined cardiologic and/or renal impairment. All types of cerebrovascular disorders should be screened for FD, including patients with white matter lesions possibly related to cerebral vasculopathy at brain MRI. [ABSTRACT FROM AUTHOR]

Aims Vulnerable plaques are characterized by a high macrophage content. We investigated the optical coherence tomography (OCT) capability of identifying coronary plaque macrophage presence using tissue property indexes. Methods and results Fifteen epicardial coronary arteries were imaged by OCT and subsequently analysed by histology. Correlating OCT- histological sections were identified and regions of interest (ROIs) were selected on both atherosclerotic plaques and normal appearing vessel tracts. OCT-derived tissue property indexes named normalized standard deviation (NSD), signal attenuation, and granulometry index were applied on ROIs to identify inflamed ROIs defined as a macrophage percentage > 10 by histology. Forty-three paired samples (OCT frame and histology section) were considered suitable as ROIs for analysis. Eleven out of 43 ROIs were considered inflamed and the remaining 32 ROIs were non-inflamed on the basis of histological count of macrophage percentage. All OCT-derived tissue property indexes were positively correlated with macrophage percentage (P = 0.0001 for all). Receiver operating characteristic curve analysis showed that NSD, granulometry index, and signal attenuation had a significant area under the curve (area = 0.906, 0.804, and 0.793, respectively). A two-step algorithm requiring to first apply NSD with a cut-off value of 0.0570 followed by granulometry index was able to identify an inflamed ROI with a sensitivity of 100% and a specificity of 96.8%. Conclusion OCT was able to identify and quantify macrophage presence in coronary artery specimens using tissue property indexes. NSD and granulometry index showed the highest accuracy in identifying a significant plaque inflammation, especially if used together in a two-step algorithm. [ABSTRACT FROM AUTHOR]

Background Basal cell carcinoma ( BCC) is the most frequent malignant tumor of the skin. The high prevalence of BCC, the risk of local recurrence, and the difficult clinical identification of the excision margins emphasize the importance of studying new approaches, ensuring complete surgical excision that allows preservation of normal tissue, especially for BCCs located on cosmetically important areas such as the mid face. Photodiagnosis ( PD) is a pre-operative technique that allows a more accurate distinction of neoplastic lesions from surrounding healthy skin in vivo. Purpose The aim of this study is to assess the usefulness of PD for the evaluation of tumor margins in 10 patients with recurrent BCC of the face. Methods We study the red fluorescence emitted by neoplastic tissue under a Wood's lamp irradiation, after accumulation of methyl amino levulinate ( MAL) cream in 10 patients with recurrent BCC. Results Our histologic analysis of perilesional skin by PD allowed to delineate more precise tumor margins, thus achieving radical excision in 90% of patients. Conclusion PD represents a diagnostic method that helps to distinguish between tumor tissue and surrounding healthy tissue especially in case of recurrent BCC of the face when the clinical delimitation is not clear. [ABSTRACT FROM AUTHOR]