MINOCA Associated with a Myocardial Bridge: Pathogenesis, Diagnosis and Treatment

Myocardial bridging (MB) is the most frequent congenital coronary anomaly characterized by a segment of an epicardial coronary artery that passes through the myocardium. MB is an important cause of myocardial ischemia and is also emerging as a possible cause of myocardial infarction with non-obstructed coronary arteries (MINOCA). There are multiple mechanisms underlying MINOCA in patients with MB (i.e., MB-mediated increased risk of epicardial or microvascular coronary spasm, atherosclerotic plaque disruption and spontaneous coronary artery dissection). The identification of the exact pathogenetic mechanism is crucial in order to establish a patient-tailored therapy. This review provides the most up-to-date evidence regarding the pathophysiology of MINOCA in patients with MB. Moreover, it focuses on the available diagnostic tools that could be implemented at the time of coronary angiography to achieve a pathophysiologic diagnosis. Finally, it focuses on the therapeutic implications associated with the different pathogenetic mechanisms of MINOCA in patients with MB

Excessive daytime sleepiness in myotonic dystrophy: a narrative review

IntroductionExcessive daytime sleepiness (EDS) is a common and debilitating symptom in both forms of myotonic dystrophy (DM), significantly impacting patients’ quality of life. The review focuses on the purpose of examining the current understanding of EDS in these conditions, the difficulty in correctly accessing it, the recent findings related to its etiology and prevalence, and a summary of potential therapeutic implications.MethodsWe conducted a comprehensive search through PubMed, selecting studies that provided significant insights into the mechanisms, prevalence, and management of EDS in DM1 and DM2.Results and discussionEDS is highly prevalent in both DM1 and DM2. Polysomnographic studies have revealed prominent dysregulation of REM sleep in DM1, suggesting a possible narcoleptic-like phenotype and alterations in NREM sleep that contributes to daytime sleepiness. Other factors have been proposed to explain EDS in DM1, including dysregulation of the sleep-wake circadian rhythm through nocturnal actigraphy analysis. The central origin of EDS is increasingly delineated supported by serotonin and orexin pathways dysfunction, and recent neuroradiological findings showing that in DM1 hippocampus volume was positively correlated with self-reported fatigue and somnolence. Sleep-disordered breathing and respiratory dysfunctions are prevalent in DM, their direct correlation with EDS remains complex and inconclusive, but respiratory evaluation should be recommended if obstructive sleep apneas or respiratory muscle dysfunctions are suspected. Drug interventions, such as modafinil and mexiletine, have shown promise in managing excessive daytime sleepiness and reducing myotonia without significant cardiac conduction effects. Enhancing EDS management in myotonic dystrophy is key to improving overall patient well-being

Episodes of Fall Asleep During Day Time in an Elder Woman with Vascular Dementia: Impact on Cerebral Ischeamic Tolerance and Utility of ECG Holter Monitoring

Here we report the case of an 86-year-old woman with advanced dementia addressed to our service for routinary ECG Holter Monitoring (EHM) for bradycardia in AV block type I. Several day-time episodes of fall-asleep while sitting had been previously reported by the nurse and generally attributed to the dementia itself, without taking into consideration the hypothesis of an AV block. The EHM reading reported several and often subsequent pauses (561), many of them critical, the longest lasting 15,9 s with no changes in clinical condition of the patient. The results of the EHM were reported to the physicians in charge for the patient and subsequently the woman was referred to the arrhythmology unit for pace-maker device implantation. Generalizing our experience, we suggest that advanced dementia, often associated with episodes of fall-asleep, could mask a conduction disturbance causing critical pauses with syncope; therefore we suggest screening those patients for possible arrhythmic disorders. Finally, we remark that in our patient the pauses weren’t associated with a worsening of the patient as seen in the follow-up, and this fact supports the hypothesis that vascular dementia could increase cerebral ischaemic tolerance

ANCA-associated vasculitis in childhood: Recent advances

Abstract Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare systemic diseases that usually occur in adulthood. They comprise granulomatosis with polyangiitis (GPA, Wegener’s), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Their clinical presentation is often heterogeneous, with frequent involvement of the respiratory tract, the kidney, the skin and the joints. ANCA-associated vasculitis is rare in childhood but North-American and European cohort studies performed during the last decade have clarified their phenotype, patterns of renal involvement and their prognostic implications, and outcome. Herein, we review the main clinical and therapeutic aspects of childhood-onset ANCA-associated vasculitis, and provide preliminary data on demographic characteristics and organ manifestations of an Italian multicentre cohort

Additional value of cardiac magnetic resonance feature tracking parameters for the evaluation of the arrhythmic risk in patients with mitral valve prolapse

Objectives: The identification of patients with mitral valve prolapse (MVP) presenting high arrhythmic risk remains challenging. Cardiovascular Magnetic Resonance (CMR) feature tracking (FT) may improve risk stratification. We analyzed the role of CMR-FT parameters in relation to the incidence of complex ventricular arrhythmias (cVA) in patients with MVP and mitral annular disjunction (MAD). Methods: 42 patients with MVP and MAD who underwent 1.5 T CMR were classified as MAD-cVA (n = 23, 55%) in case of cVA diagnosed on a 24-h Holter monitoring and as MAD-noVA in the absence of cVA (n = 19, 45%). MAD length, late gadolinium enhancement (LGE), basal segments myocardial extracellular volume (ECV) and CMR-FT were assessed. Results: LGE was more frequent in the MAD-cVA group in comparison with the MAD-noVA group (78% vs 42%, p = 0.002) while no difference was observed in terms of basal ECV. Global longitudinal strain (GLS) was reduced in MAD-cVA compared to MAD-noVA (− 18.2% ± 4.6% vs − 25.1% ± 3.1%, p = 0.004) as well as global circumferential strain (GCS) at the mid-ventricular level (− 17.5% ± 4.7% vs − 21.6% ± 3.1%, p = 0.041). Univariate analysis identified as predictors of the incidence of cVA: GCS, circumferential strain (CS) in the basal and mid infero-lateral wall, GLS, regional longitudinal strain (LS) in the basal and mid-ventricular inferolateral wall. Reduced GLS [Odd ratio (OR):1.56 (confidence interval (CI) 95%: 1.45–2.47; p < 0.001)] and regional LS in the basal inferolateral wall [OR: 1.62 (CI 95%: 1.22–2.13; p < 0.001)] remained independent prognostic factors in multivariate analysis. Conclusion: In patients with MVP and MAD, CMR-FT parameters are correlated with the incidence of cVA and may be of interest in arrhythmic risk stratification

Multimodality Imaging Evaluation to Detect Subtle Right Ventricular Involvement in Patients with Acute Myocarditis and Preserved Left Ventricular Ejection Fraction

Background: Evaluation of the right ventricle (RV) in patients with acute myocarditis (MY) remains challenging with both 2D transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR). We examined the incremental diagnostic value of CMR feature tracking (FT) to evaluate RV involvement in patients with myocarditis. Methods: We enrolled 54 patients with myocarditis and preserved left ventricle (LV) ejection fraction (EF). The CMR protocol included T2-weighted images for edema detection and late gadolinium enhancement (LGE) images. Global longitudinal strain (GLS) of the left ventricle (LV) and RV free wall strain (CMR-FWS) were obtained with CMR-FT. We identified 34 patients (62%) with inferior and lateral segment (IL-MY) involvement and 20 (38%) noIL-MY in case of any other myocardial segment involved. Here, 20 individuals who underwent CMR for suspected cardiac disease, which was not confirmed thereafter, were considered as the control population. Results: TTE and CMR showed normal RV function in all patients without visible RV involvement at the LGE or T2-weighted sequences. At CMR, LV-GLS values were significantly lower in patients with MY compared to the control group (median −19.0% vs. −21.0%, p = 0.029). Overall, CMR RV-FWS was no different between MY patients and controls (median −21.2% vs. −23.2 %, p = 0.201) while a significant difference was found between RV FWS in IL-MY and noIL-MY (median −18.17% vs. −24.2%, p = 0.004). Conclusions: CMR-FT has the potential to unravel subclinical RV involvement in patients with acute myocarditis, specifically in those with inferior and lateral injuries that exhibit lower RV-FWS values. In this setting, RV deformation analysis at CMR may be effectively implemented for a comprehensive functional assessment

No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study

Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.Fil: Dominguez Valentin, Mev. St Mark’s Hospital; Reino Unido. The Norwegian Radium Hospital; Noruega. European Hereditary Tumour Group; Reino UnidoFil: Plazzer, John Paul. St Mark’s Hospital; Reino Unido. The Royal Melbourne Hospital; AustraliaFil: Sampson, Julian R.. European Hereditary Tumour Group; Reino Unido. Cardiff University; Reino UnidoFil: Engel, Christoph. European Hereditary Tumour Group; Reino Unido. Universitat Leipzig; AlemaniaFil: Aretz, Stefan. Universitat Bonn; AlemaniaFil: Jenkins, Mark A.. University of Melbourne; AustraliaFil: Sunde, Lone. Aalborg University; DinamarcaFil: Bernstein, Inge. Aalborg University; DinamarcaFil: Capella, Gabriel. European Hereditary Tumour Group; Reino Unido. St Mark’s Hospital; Reino Unido. Institut Català d’Oncologia; EspañaFil: Balaguer Prunés, Francesc. Universidad de Barcelona; EspañaFil: Macrae, Finlay. European Hereditary Tumour Group; Reino Unido. The Royal Melbourne Hospital; AustraliaFil: Winship, Ingrid M.. University of Melbourne; AustraliaFil: Thomas, Huw. Imperial College London; Reino UnidoFil: Evans, Dafydd Gareth. University of Manchester; Reino UnidoFil: Burn, John. Universidad de Newcastle; Australia. The Royal Melbourne Hospital; Australia. St Mark’s Hospital; Reino UnidoFil: Greenblatt, Marc. University of Vermont; Estados UnidosFil: de Vos tot Nederveen Cappel, Wouter H.. Isala Clinics; Países BajosFil: Sijmons, Rolf H.. University of Groningen; Países Bajos. St Mark’s Hospital; Reino Unido. European Hereditary Tumour Group; Reino UnidoFil: Nielsen, Maartje. Leids Universitair Medisch Centrum; Países BajosFil: Bertario, Lucio. Fondazione IRCCS Istituto Nazionale dei Tumori; ItaliaFil: Bonanni, Bernardo. Fondazione IRCCS Istituto Nazionale dei Tumori; ItaliaFil: Tibiletti, Maria Grazia. Università dell’Insubria; ItaliaFil: Cavestro, Giulia Martina. Vita-Salute San Raffaele University; ItaliaFil: Lindblom, Annika. Karolinska Huddinge Hospital; SueciaFil: Della Valle, Adriana. Hospital Fuerzas Armadas; UruguayFil: Lopez Kostner, Francisco. Clínica Universidad de los Andes; ChileFil: Alvarez, Karin. Clínica Universidad de los Andes; ChileFil: Gluck, Nathan. Universitat Tel Aviv; IsraelFil: Katz, Lior. Sheba Medical Center; IsraelFil: Heinimann, Karl. University Hospital Basel; SuizaFil: Piñero, Tamara Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; ArgentinaFil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentin

Risk-Reducing Gynecological Surgery in Lynch Syndrome : Results of an International Survey from the Prospective Lynch Syndrome Database

Purpose: To survey risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) practice and advice regarding hormone replacement therapy (HRT) in women with Lynch syndrome. Methods: We conducted a survey in 31 contributing centers from the Prospective Lynch Syndrome Database (PLSD), which incorporates 18 countries worldwide. The survey covered local policies for risk-reducing hysterectomy and BSO in Lynch syndrome, the timing when these measures are offered, the involvement of stakeholders and advice regarding HRT. Results: Risk-reducing hysterectomy and BSO are offered to path_MLH1 and path_MSH2 carriers in 20/21 (95%) contributing centers, to path_MSH6 carriers in 19/21 (91%) and to path_PMS2 carriers in 14/21 (67%). Regarding the involvement of stakeholders, there is global agreement (similar to 90%) that risk-reducing surgery should be offered to women, and that this discussion may involve gynecologists, genetic counselors and/or medical geneticists. Prescription of estrogen-only HRT is offered by 15/21 (71%) centers to women of variable age range (35-55 years). Conclusions: Most centers offer risk-reducing gynecological surgery to carriers of path_MLH1, path_MSH2 and path_MSH6 variants but less so for path_PMS2 carriers. There is wide variation in how, when and to whom this is offered. The Manchester International Consensus Group developed recommendations to harmonize clinical practice across centers, but there is a clear need for more research.Peer reviewe