Cardiac Magnetic Resonance Feature-Tracking Identifies Preclinical Abnormalities in Hypertrophic Cardiomyopathy Sarcomere Gene Mutation Carriers.

BACKGROUND: Assessing myocardial strain by cardiac magnetic resonance feature tracking (FT) has been found to be useful in patients with overt hypertrophic cardiomyopathy (HCM). Little is known, however, of its role in sarcomere gene mutation carriers without overt left ventricular hypertrophy (subclinical HCM). METHODS: Thirty-eight subclinical HCM subjects and 42 healthy volunteers were enrolled in this multicenter case-control study. They underwent a comprehensive cardiac magnetic resonance study. Two-dimensional global radial, circumferential, and longitudinal strain of the left ventricle (LV) were evaluated by FT analysis. RESULTS: The subclinical HCM sample was 41 (22-51) years old and 32% were men. FT analysis revealed a reduction in global radial strain (29±7.2 versus 47.9±7.4; P<0.0001), global circumferential strain (-17.3±2.6 -versus -20.8±7.4; P<0.0001) and global longitudinal strain (-16.9±2.4 versus -20.5±2.6; P<0.0001) in subclinical HCM compared with control subjects. The significant differences persisted when considering the 23 individuals free of all the structural and functional ECG and cardiac magnetic resonance abnormalities previously described. Receiver operating characteristic curve analyses showed that the differential diagnostic performances of FT in discriminating subclinical HCM from normal subjects were good to excellent (global radial strain with optimal cut-off value of 40.43%: AUC, 0.946 [95% CI, 0.93-1.00]; sensitivity 90.48%, specificity 94.44%; global circumferential strain with cut-off, -18.54%: AUC, 0.849 [95% CI, 0.76-0.94]; sensitivity, 88.10%; specificity, 72.22%; global longitudinal strain with cut-off, -19.06%: AUC, 0.843 [95% CI, 0.76-0.93]; sensitivity, 78.57%; specificity, 78.95%). Similar values were found for discriminating those subclinical HCM subjects without other phenotypic abnormalities from healthy volunteers (global radial strain with optimal cut-off 40.43%: AUC, 0.966 [95% CI, 0.92-1.00]; sensitivity, 90.48%; specificity, 95.45%; global circumferential strain with cut-off, -18.44%: AUC, 0.866 [95% CI, 0.76-0.96]; sensitivity, 92.86%; specificity, 77.27%; global longitudinal strain with cut-off, -17.32%: AUC, 0.838 [95% CI, 0.73-0.94]; sensitivity, 90.48%; specificity, 65.22%). CONCLUSIONS: Cardiac magnetic resonance FT-derived parameters are consistently lower in subclinical patients with HCM, and they could emerge as a good tool for discovering the disease during a preclinical phase.

Atrial electrofunctional predictors of incident atrial fibrillation in cardiac amyloidosis.

BACKGROUND: Atrial fibrillation (AF) is common in patients with cardiac amyloidosis (CA) and is a significant risk factor for heart failure hospitalization and thromboembolic events. OBJECTIVE: This study was designed to investigate the atrial electrofunctional predictors of incident AF in CA. METHODS: A multicenter, observational study was conducted in 4 CA referral centers including sinus rhythm patients with light-chain (AL) and transthyretin (ATTR) CA undergoing electrocardiography and cardiac magnetic resonance imaging. The primary end point was new-onset AF occurrence. RESULTS: Overall, 96 patients (AL-CA, n = 40; ATTR-CA, n = 56) were enrolled. During an 18-month median follow-up (Q1-Q3, 7-29 months), 30 patients (29%) had incident AF. Compared with those without AF, patients with AF were older (79 vs 73 years; P = .001). They more frequently had ATTR (87% vs 45%; P < .001); electrocardiographic interatrial block (IAB), either partial (47% vs 21%; P = .011) or advanced (17% vs 3%; P = .017); and lower left atrial ejection fraction (LAEF; 29% vs 41%; P = .004). Age (hazard ratio [HR], 1.059; 95% CI, 1.002-1.118; P = .042), any type of IAB (HR, 2.211; 95% CI, 1.03-4.75; P = .041), and LAEF (HR, 0.967; 95% CI, 0.936-0.998; P = .044) emerged as independent predictors of incident AF. Patients exhibiting any type of IAB, LAEF <40%, and age >78 years showed a cumulative incidence for AF of 40% at 12 months. This risk was significantly higher than that carried by 1 (8.5%) or none (7.6%) of these 3 risk factors. CONCLUSION: In patients with CA, older age, IAB on 12-lead electrocardiography, and reduced LAEF on cardiac magnetic resonance imaging are significant and independent predictors of incident AF. A closer screening for AF is advisable in CA patients carrying these features.

Pathogens in Crohn's Disease: The Role of Adherent Invasive Escherichia coli.

In Crohn's disease (CD), gut dysbiosis is marked by the prevalence of pathogenic bacterial species. Although several microbes have been reported as risk factors or causative agents of CD, it is not yet clear which is the real trigger of the disease. Thirty years ago, a new pathovar of Escherichia coli strain was isolated in the ileal mucosa of CD patients. This strain, called adherent invasive E. coli (AIEC), for its ability to invade the intestinal mucosa, could represent the causative agent of the disease. Several authors studied the mechanisms by which the AIEC penetrate and replicate within macrophages, and release inflammatory cytokines sustaining inflammation. In this review we will discuss about the role of AIEC in the pathogenesis of CD, the virulence factors mediating adhesion and invasion of AIEC in mucosal tissue, the environmental conditions improving AIEC survival and replication within macrophages. Finally, we will also give an overview of the new strategies developed to limit AIEC overgrowth.

Bioprosthetic pulmonary valve dysfunction in a primary cardiac sarcoma survivor: Clinical considerations and treatment options.

The case highlights the good survival after radical surgery and chemotherapy of a cardiac sarcoma, and the need for close follow-up due to possible early postsurgical complications.

Leukocytes and Endothelial Cells Participate in the Pathogenesis of Alzheimer's Disease: Identifying New Biomarkers Mirroring Metabolic Alterations.

Alzheimer's disease (AD) is a neurodegenerative disorder marked by amyloid-ß accumulation, tau dysfunction, and neuroinflammation, involving endothelial cells and leukocytes. The breakdown of the blood-brain barrier allows immune cell infiltration, intensifying inflammation. A decreased ratio of Connexin-37 (Cx37, also known as GJA4: Gap Junction Protein Alpha 4) and Prolyl Hydroxylase Domain-Containing Protein 3 (PHD3, also known as EGLN3: Egl-9 Family Hypoxia Inducible Factor 3), Cx37/PHD3, consistently observed in different AD-related models, may represent a novel potential biomarker of AD, albeit the exact mechanisms underlying this phenomenon, most likely based on gap junction-mediated cellular interaction that modulate the cellular metabolite status, remain to be fully elucidated.

Role of arrhythmic phenotype in prognostic stratification and management of dilated cardiomyopathy.

AIMS: Dilated cardiomyopathy (DCM) with arrhythmic phenotype combines phenotypical aspects of DCM and predisposition to ventricular arrhythmias, typical of arrhythmogenic cardiomyopathy. The definition of DCM with arrhythmic phenotype is not universally accepted, leading to uncertainty in the identification of high-risk patients. This study aimed to assess the prognostic impact of arrhythmic phenotype in risk stratification and the correlation of arrhythmic markers with high-risk arrhythmogenic gene variants in DCM patients. METHODS AND RESULTS: In this multicentre study, DCM patients with available genetic testing were analysed. The following arrhythmic markers, present at baseline or within 1 year of enrolment, were tested: unexplained syncope, rapid non-sustained ventricular tachycardia (NSVT), ≥1000 premature ventricular contractions/24 h or ≥50 ventricular couplets/24 h. LMNA, FLNC, RBM20, and desmosomal pathogenic or likely pathogenic gene variants were considered high-risk arrhythmogenic genes. The study endpoint was a composite of sudden cardiac death and major ventricular arrhythmias (SCD/MVA). We studied 742 DCM patients (45 ± 14 years, 34% female, 410 [55%] with left ventricular ejection fraction [LVEF] <35%). During a median follow-up of 6 years (interquartile range 1.6-12.1), unexplained syncope and NSVT were the only arrhythmic markers associated with SCD/MVA, and the combination of the two markers carried a significant additive risk of SCD/MVA, incremental to LVEF and New York Heart Association class. The probability of identifying an arrhythmogenic genotype rose from 8% to 30% if both early syncope and NSVT were present. CONCLUSION: In DCM patients, the combination of early detected NSVT and unexplained syncope increases the risk of life-threatening arrhythmic outcomes and can aid the identification of carriers of malignant arrhythmogenic genotypes.

Antibiotic Therapy for Active Crohn's Disease Targeting Pathogens: An Overview and Update.

Crohn's disease (CD) is a multifactorial chronic disorder that involves a combination of factors, including genetics, immune response, and gut microbiota. Therapy includes salicylates, immunosuppressive agents, corticosteroids, and biologic drugs. International guidelines do not recommend the use of antibiotics for CD patients, except in the case of septic complications. Increasing evidence of the involvement of gut bacteria in this chronic disease supports the rationale for using antibiotics as the primary treatment for active CD. In recent decades, several pathogens have been reported to be involved in the development of CD, but only Escherichia coli (E. coli) and Mycobacterium avium paratubercolosis (MAP) have aroused interest due to their strong association with CD pathogenesis. Several meta-analyses have been published concerning antibiotic treatment for CD patients, but randomized trials testing antibiotic treatment against E. coli and MAP have not shown prolonged benefits and have generated conflicting results; several questions are still unresolved regarding trial design, antibiotic dosing, the formulation used, the treatment course, and the outcome measures. In this paper, we provide an overview and update of the trials testing antibiotic treatment for active CD patients, taking into account the role of pathogens, the mechanisms by which different antibiotics act on harmful pathogens, and antibiotic resistance. Finally, we also present new lines of study for the future regarding the use of antibiotics to treat patients with active CD.

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Lateral Pectoral Nerve Identification through Ultrasound-Guided Methylene Blue Injection during Selective Peripheral Neurectomy for Shoulder Spasticity: Proposal for a New Procedure.

Internally rotated and adducted shoulder is a common posture in upper limb spasticity. Selective peripheral neurectomy is a useful and viable surgical technique to ameliorate spasticity, and the lateral pectoral nerve (LPN) could be a potential good target to manage shoulder spasticity presenting with internal rotation. However, there are some limitations related to this procedure, such as potential anatomical variability and the necessity of intraoperative surgical exploration to identify the target nerve requiring wide surgical incisions. This could result in higher post-surgical discomfort for the patient. Therefore, the aim of our study was to describe a modification of the traditional selective peripheral neurectomy procedure of the LPN through the perioperative ultrasound-guided marking of the target nerve with methylene blue. The details of the localization and marking procedure are described, as well as the surgical technique of peripheral selective neurectomy and the potential advantages in terms of nerve localization, surgical precision and patients' post-surgical discomfort. We suggest that the proposed modified procedure could be a valid technique to address some current limitations and move the surgical treatment of spasticity toward increasingly tailored management due to the ease of nerve identification, the possibility of handling potential anatomical variability and the resulting smaller surgical incisions.

Cefiderocol Versus Colistin for the Treatment of Carbapenem-Resistant Acinetobacter baumannii Complex Bloodstream Infections: A Retrospective, Propensity-Score Adjusted, Monocentric Cohort Study.

INTRODUCTION: Bloodstream infections (BSI) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are associated with high mortality with limited treatment. The aim of this study is to compare effectiveness and safety of colistin-based versus cefiderocol-based therapies for CRAB-BSI. METHODS: This is a retrospective observational study enrolling patients with monomicrobial CRAB-BSIs treated with colistin or cefiderocol from 1 January 2020, to 31 December 2022. The 30-day all-cause mortality rate was the primary outcome. A Cox regression analysis was performed to identify factors independently associated with mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. RESULTS: Overall 118 patients were enrolled, 75 (63%) and 43 (37%) treated with colistin- and cefiderocol-based regimens. The median (q1-q3) age was 70 (62-79) years; 70 (59%) patients were men. The 30-day all-cause mortality was 52%, significantly lower in the cefiderocol group (40% vs 59%, p = 0.045). By performing a Cox regression model, age (aHR = 1.03, 95% CI 1.00-1.05), septic shock (aHR = 1.93, 95% CI 1.05-3.53), and delayed targeted therapy (aHR = 2.42, 95% CI 1.11-5.25) were independent predictors of mortality, while cefiderocol-based therapy was protective (aHR = 0.49, 95% CI 0.25-0.93). The IPTW-adjusted Cox analysis confirmed the protective effect of cefiderocol (aHR = 0.53, 95% CI 0.27-0.98). CONCLUSIONS: Cefiderocol may be a valuable treatment option for CRAB-BSI, especially in the current context of limited treatment options.

Acute Foot Drop Caused by Intraneural Ganglion Cyst of the Peroneal Nerve: Literature Review and Case Report.

BACKGROUND: Foot drop (FD) is characterized by an inability to lift the foot against gravity because of dorsiflexor muscle weakness. The aim of the present study is to report a clinical case of acute non-traumatic FD in patients with peroneal intraneural ganglion, after performing a scoping review on the methodological management of this disease. METHODS: We performed a review of the literature and reported the case of a 49-year-old man with acute FD caused by an intraneural ganglion cyst of the peroneal nerve. RESULTS: Out of a total of 201 articles, 3 were suitable for our review beyond our case report. The acute FD caused by peroneal intraneural ganglion can be managed by a careful clinical-instrumental differential diagnosis. A targeted surgery with subsequent rehabilitation produced a satisfactory motor recovery. CONCLUSIONS: Acute FD requires an appropriate diagnostic-therapeutic framework to identify and effectively treat the causes in order to promote complete recovery.

Sagittal kinematics and imbalance of the spine and whole body during walking in late-onset Pompe disease.

Late-onset Pompe disease (LOPD) is characterized by postural abnormalities mainly due to involvement of paraspinal lumbar and abdominal-pelvic muscles. Previous studies quantitatively analyzed static upright posture, spatial-temporal parameters, and kinematics of the lower limbs and trunk, considered as single bone segment. Sagittal plane analysis of the spine and whole body during walking has never been investigated in patients with LOPD. The aim of the study was to evaluate sagittal kinematics and imbalance of the spine and whole body in patients with LOPD by three-dimensional (3-D)-motion analysis using an appropriate marker set protocol and introducing innovative kinematic parameters. Seven siblings with LOPD were assessed by 3-D-stereophotogrammetry using the DB-total protocol, which allows to analyze sagittal alignment of whole body. Fourteen age- and sex-matched healthy subjects were used as controls. LOPD group showed a flattening of the spinal curvatures, with a head and neck posteriorization with respect to sacrum, a significant increase of concavity in Heel-S2-Nasion/C7 angles, a rear-position of upper limbs with respect to pelvis, a shorter pendular activity, and a trend of elbow extension during ambulation. Moreover, a significant increase of excursion range in most of sagittal parameters was found. The present study highlighted a specific pathological postural pattern, resembling "man falling backwards," which reveals a biomechanical compensation strategy of patients with LOPD to maintain the balance against the instability of the spinopelvic region, kinematically verified by increase of the excursion ranges. DB-total kinematic parameters might be useful for functional evaluation and for monitoring response to enzyme replacement therapy, rehabilitation project, and disease progression.NEW & NOTEWORTHY This study is the first to quantitatively characterize the sagittal spine and whole body posture of patients with late-onset Pompe disease during walking, showing a pathological kinematic pattern defined "man falling backwards." 3-D-motion analysis, with a specific marker set (DB-total protocol) introducing new whole body kinematic parameters, may be useful for accurate functional evaluation and monitoring this rare disease.

Sialylation status in placentas from pregnancies with SARS-CoV-2 infection.

INTRODUCTION: Recent investigations suggest the potential negative impact of SARS-CoV-2 infection on pregnant women and pregnancy outcome. In addition, some studies have described pathological changes in the placental tissue of SARS-CoV-2-positive mothers, which are related or not to the infection severity and/or infection trimester. Among the various molecules involved in the normal structure and functionality of the placenta, sialic acids (Sias) seem to play an important role. Hence, we aimed to investigate possible changes in the distribution and content of Sias with different glycosidic linkages, namely α2,3 and α2,6 Galactose- or N-acetyl-Galactosamine-linked Sias and polymeric Sia (PolySia), in placentas from pregnant women infected by SARS-CoV-2 during the three different pregnancy trimesters. METHODS: α2,3 and α2,6 Galactose-linked Sias were evaluated by lectin histochemistry (Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA), respectively), while immunohistochemistry was used for PolySia detection. RESULTS: Data showed lower levels of α2,3 Galactose-linked Sias in the trophoblast and underlying basement membrane/basal plasma membrane in placentas from women infected during the second and third infection trimester compared with uninfected cases and those infected during first trimester. On the other hand, higher levels of PolySia were detected in the trophoblast during the second and third infection trimester. CONCLUSIONS: Our findings suggest that changes in the sialylation status of trophoblast and its basement membrane/basal plasma membrane, together with other concomitant factors, could be at the basis of the most common placental histopathological alterations and gestational complications found especially in pregnancies with SARS-CoV-2 infection during the second and third trimester.

Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.

The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.

miR-4432 Targets FGFBP1 in Human Endothelial Cells.

MicroRNAs (miRs) are small non-coding RNAs that modulate the expression of several target genes. Fibroblast growth factor binding protein 1 (FGFBP1) has been associated with endothelial dysfunction at the level of the blood-brain barrier (BBB). However, the underlying mechanisms are mostly unknown and there are no studies investigating the relationship between miRs and FGFBP1. Thus, the overarching aim of the present study was to identify and validate which miR can specifically target FGFBP1 in human brain microvascular endothelial cells, which represent the best in vitro model of the BBB. We were able to identify and validate miR-4432 as a fundamental modulator of FGFBP1 and we demonstrated that miR-4432 significantly reduces mitochondrial oxidative stress, a well-established pathophysiological hallmark of hypertension.

In-Plane and Out-of-Plane Investigation of Resonant Tunneling Polaritons in Metal-Dielectric-Metal Cavities.

Polaritons can be generated by tuning the optical transitions of a light emitter to the resonances of a photonic cavity. We show that a dye-doped cavity generates resonant tunneling polaritons with Epsilon-Near-Zero (ENZ) effective permittivity. We studied the polariton spectral dispersion in dye-doped metal-dielectric-metal (MDM) cavities as a function of the in-plane (k||) and out-of-plane (k⊥) components of the incident wavevector. The dependence on k|| was investigated through ellipsometry, revealing the ENZ modes. The k⊥ dependence was measured by varying the cavity thickness under normal incidence using a Surface Force Apparatus (SFA). Both methods revealed a large Rabi splitting well exceeding 100 meV. The SFA-based investigation highlighted the collective nature of strong coupling by producing a splitting proportional to the square root of the involved photons. This study demonstrates the possibility of generating ENZ polaritons and introduces the SFA as a powerful tool for the characterization of strong light-matter interactions.

Antiinflammatory Activities of Curcumin and Spirulina: Focus on Their Role against COVID-19.

Nutraceuticals have for several years aroused the interest of researchers for their countless properties, including the management of viral infections. In the context of the COVID-19 pandemic, studies and research on the antiviral properties of nutraceuticals have greatly increased. More specifically, over the past two years, researchers have focused on analyzing the possible role of nutraceuticals in reducing the risk of SARS-CoV-2 infection or mitigating the symptoms of COVID-19. Among nutraceuticals, turmeric, extracted from the rhizome of the Curcuma Longa plant, and spirulina, commercial name of the cyanobacterium Arthrospira platensis, have assumed considerable importance in recent years. The purpose of this review is to collect, through a search of the most recent articles on Pubmed, the scientific evidence on the role of these two compounds in the fight against COVID-19. In the last two years many hypotheses, some confirmed by clinical and experimental studies, have been made on the possible use of turmeric against COVID-19, while on spirulina and its possible role against SARS-CoV-2 infection information is much less. The demonstrated antiviral properties of spirulina and the fact that these cyanobacteria may modulate or modify some mechanisms also involved in the onset of COVID-19, lead us to think that it may have the same importance as curcumin in fighting this disease and to speculate on the possible combined use of these two substances to obtain a synergistic effect.

SARS-CoV-2 Infection: A Clinical and Histopathological Study in Pregnancy.

During pregnancy, SARS-CoV-2 infection is associated with several adverse outcomes, including an increased risk of pre-eclampsia, preterm delivery, hypertensive disorders, gestational diabetes, and fetal growth restriction related to the development of placenta vascular abnormalities. We analyzed human placenta from full-term, uncomplicated pregnancies with SARS-CoV-2 infection during the first, second, or third trimesters of gestation. We studied, by the immunohistochemistry technique, the expression of CD34 and podoplanin (PDPN) as markers of vasculogenesis to find any differences. As secondary outcomes, we correlated maternal symptoms with placental histological alterations, including fibrin deposits, lymphocyte infiltration in the villi, edema, and thrombi. Our results showed a PDPN expression around the villous stroma as a plexiform network around the villous nucleus of fetal vessels; significant down-regulation was observed in the villous stroma of women infected during the third trimester. CD34 showed no changes in expression levels. During SARS-CoV-2 infection, the most common maternal symptoms were fever, anosmia, ageusia and asthenia, and the majority were treated with paracetamol, corticosteroids and azithromycin. Patients that required multiple symptomatic treatments evidenced a large amount of fibrin deposition in the villi. Certainly, PDPN plays a key role in healthy placental vasculogenesis and thus in its proper physiology, and SARS-CoV-2 surely alters its normal expression. Further studies are necessary to understand what mechanisms are being altered to try to avoid possible complications for both the mother and fetus in terms of the contagions that will still occur.

Dark papillary muscles sign: a novel prognostic marker for cardiac magnetic resonance.

OBJECTIVES: The prognostic role of left ventricular (LV) papillary muscle abnormalities in patients with preserved LV systolic ejection fraction (LVEF) is unknown. We sought to evaluate the prognosis role of LV papillary muscle abnormalities by CMR in patients with ventricular arrhythmias, preserved LVEF with no cardiac disease. METHODS: A total of 391 patients with > 500/24 h premature ventricular complexes and/or with non-sustained ventricular tachycardia (NSVT), preserved LVEF, and no cardiac disease were enrolled. Different features of LV papillary muscles were considered: supernumerary muscles, papillary thickness, the attachment, late gadolinium enhancement (LGE). Dark-Paps was defined as end-systolic signal hypointensity of both papillary muscles in early post-contrast cine CMR images. Mitral valve prolapse, mitral annular disjunction (MAD), and myocardial LGE were considered. RESULTS: Dark-Paps was found in 79 (20%) patients and was more frequent in females. It was associated with higher prevalence of mitral valve prolapse and MAD. During a median follow-up of 2534 days, 22 hard cardiac events occurred. At Kaplan-Meier curve analysis, patients with Dark-Paps were at higher risk of events than those without (p < 0.0001). Dark-Paps was significantly associated with hard cardiac events in all the multivariate models. Dark-Paps improved prognostic estimation when added to NSVT (p = 0.0006), to LGE (p = 0.005) and to a model including NSVT+LGE (p = 0.014). Dark-Paps allowed a significant net reclassification when added to NSVT (NRI 0.30, p = 0.03), to LGE (NRI 0.25, p = 0.04), and to NSVT + LGE (NRI 0.32, p  = 0.02). CONCLUSIONS: In LV papillary muscles, Dark-Paps is a novel prognostic marker in patients with ventricular arrhythmias and preserved ejection fraction. KEY POINTS: • Papillary muscle abnormalities are seen in patients with ventricular arrhythmias and preserved left ventricular ejection fraction. • Early post-contrast hypointensity of papillary muscles in end-systolic cine images (Dark-Paps) is a novel prognostic marker in patients with ventricular arrhythmias and preserved ejection fraction. • Dark-Paps had an additive prognostic role over late gadolinium enhancement and non-sustained ventricular tachycardia.