Multifocal ectopic premature Purkinje-related complexes syndrome in children.
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ABSTRACT:
SUBMITTER: Young ML
PROVIDER: S-EPMC10444558 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Multifocal ectopic premature Purkinje-related complexes syndrome in children.
Young Ming-Lon ML Kilinc Orhan O Benhayon Daniel D
HeartRhythm case reports 20230526 8
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Project description:Multifocal ectopic Purkinje-related premature contraction (MEPPC) is an autosomal dominant SCN5A channelopathy characterized by frequent multiform premature ventricular contractions originating from the His-Purkinje system. We present a patient with an MEPPC phenotype whose genetic testing identified a pathogenic SCN5A (HGNC:10593) variant amenable to precision antiarrhythmic therapy with flecainide.
| S-EPMC10920139 | biostudies-literature
Project description: Not available
| S-EPMC10285139 | biostudies-literature
Project description:BackgroundSCN5A mutations may present with different clinical phenotypes such as Brugada syndrome, long QT3 syndrome, sick sinus syndrome, atrial fibrillation, dilated cardiomyopathy, and the least known multifocal ectopic Purkinje-related premature contractions syndrome.Case summaryWe report a case of a 29-year-old woman with palpitations due to multifocal premature ventricular complexes (PVCs) and a family history of sudden death. The previous electrophysiological study had shown that PVCs arose from Purkinje fibres but catheter ablation was unsuccessful. Cardiac magnetic resonance (CMR) imaging demonstrated non-ischaemic areas of subendocardial fibrosis at multiple left ventricular (LV) segments with concomitant dilatation and mild systolic impairment. Amiodarone suppressed the ectopy but caused hyperthyroidism. Due to recent pregnancy, she received no antiarrhythmics which resulted in PVC burden increase and further deterioration of the ejection fraction (EF). After gestation, amiodarone was reinitiated and switched to flecainide after implantation of a subcutaneous defibrillator as a safety net. At follow-up, LV function had almost normalized. Genetic analysis confirmed an SCN5A mutation.DiscussionMultifocal ectopic Purkinje-related premature contractions syndrome is associated with SCN5A mutation which in our case (R222Q) is the most common described. Flecainide can be an appropriate treatment option when ablation is ineffective. Defibrillator-even a subcutaneous type-could be implanted in cases of LV dysfunction or scar. PVCs suppression by flecainide and restoration of EF implies an arrhythmia-induced mechanism of LV impairment.
| S-EPMC8086419 | biostudies-literature
Project description:BackgroundWe identified a novel SCN5A variant, E171Q, in a neonate with very frequent ectopy and reduced ejection fraction which normalized after arrhythmia suppression by flecainide. This clinical picture is consistent with multifocal ectopic Purkinje-related premature contractions (MEPPC). Most previous reports of MEPPC have implicated SCN5A variants such as R222Q that neutralize positive charges in the S4 voltage sensor helix of the channel protein NaV1.5 and generate a gating pore current.Methods and resultsE171 is a highly conserved negatively-charged residue located in the S2 transmembrane helix of NaV1.5 domain I. E171 is a key component of the Gating Charge Transfer Center, a region thought to be critical for normal movement of the S4 voltage sensor helix. We used heterologous expression, CRISPR-edited induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), and molecular dynamics simulations to demonstrate that E171Q generates a gating pore current, which was suppressed by a low concentration of flecainide (IC50 = 0.71±0.07 µM). R222Q shifts voltage dependence of activation and inactivation in a negative direction but we observed positive shifts with E171Q. E171Q iPSC-CMs demonstrated abnormal spontaneous activity and prolonged action potentials. Molecular dynamics simulations revealed that both R222Q and E171Q proteins generate a water-filled permeation pathway that underlies generation of the gating pore current.ConclusionPreviously identified MEPPC-associated variants that create gating pore currents are located in positively-charged residues in the S4 voltage sensor and generate negative shifts in the voltage dependence of activation and inactivation. We demonstrate that neutralizing a negatively charged S2 helix residue in the Gating Charge Transfer Center generates positive shifts but also create a gating pore pathway. These findings implicate the gating pore pathway as the primary functional and structural determinant of MEPPC and widen the spectrum of variants that are associated with gating pore-related disease in voltage-gated ion channels.
| S-EPMC10888965 | biostudies-literature
Project description:In some cases with idiopathic ventricular fibrillation, short-coupled premature ventricular contractions (PVCs) initiate fatal arrhythmia, which has recently been proposed as short-coupled ventricular fibrillation (SCVF). In the present case of SCVF, catheter ablation for trigger PVCs originating from the His-Purkinje system in both ventricles caused transient complete atrioventricular block, and a combination of quinidine and verapamil suppressed ventricular tachyarrhythmia. <Learning objective: In some cases with short-coupled ventricular fibrillation, a combination of quinidine and verapamil can suppress fatal ventricular tachyarrhythmia.>.
| S-EPMC9169001 | biostudies-literature
Project description:IntroductionIntracranial germinomas mainly arise in the pineal gland or neurohypophyseal region. The basal ganglia have been reported as the site of occurrence for ectopic germinomas, whereas other sites have been rarely described. We experienced a case of multifocal ectopic germinoma that arose in the septum pellucidum and the dorsal brain stem, not including the pineal gland, neurohypophysis, and basal ganglia of ectopic germinoma in a pregnant woman.Case presentationThe patient initially presented to our institution with complaints of diplopia in the past 14 weeks of gestation, and imaging later revealed two intracranial neoplastic lesions, with one lesion involving the septum pellucidum and the other involving the dorsal brainstem. Both tumors were partially excised via a transcortical approach. Based on the results of pathology and immunohistochemistry, the patient was diagnosed with germinoma, and the intraoperative spinal fluid cytology was class V in Papanicolaou classification. The patient received three courses of ifosfamide, carboplatin, and etoposide together with whole-brain irradiation, which resulted in complete elimination of the tumors. No evidence of recurrence was identified after 18 months.ConclusionThe results illustrated the need to consider germinoma in the differential diagnosis if the lesions involve midline structures such as the septum pellucidum or dorsal brainstem. Given the rarity of germinoma arising outside the pineal gland and neurohypophyseal region, these findings provide key insights into the diagnosis and treatment of this disease.
| S-EPMC10978038 | biostudies-literature
Project description:The occurrence of early afterdepolarizations (EADs) and increased dispersion of repolarization are two known factors for arrhythmogenesis in long QT syndrome. However, increased dispersion of repolarization tends to suppress EADs due to the source-sink effect, and thus how the two competing factors cause initiation of arrhythmias remains incompletely understood. Here we used optical mapping and computer simulation to investigate the mechanisms underlying spontaneous initiation of arrhythmias in type 2 long QT (LQT2) syndrome. In optical mapping experiments of transgenic LQT2 rabbit hearts under isoproterenol, premature ventricular complexes (PVCs) were observed to originate from the steep spatial repolarization gradient (RG) regions and propagated unidirectionally. The same PVC behaviors were demonstrated in computer simulations of tissue models of rabbits. Depending on the heterogeneities, these PVCs could lead to either repetitive focal excitations or reentry without requiring an additional vulnerable substrate. Systematic simulations showed that cellular phase 2 EADs were either suppressed or confined to the long action potential region due to the source-sink effect. Tissue-scale phase 3 EADs and PVCs occurred due to tissue-scale dynamical instabilities caused by RG and enhanced L-type calcium current (ICa,L), occurring under both large and small RG. Presence of cellular EADs was not required but potentiated PVCs when RG was small. We also investigated how other factors affect the dynamical instabilities causing PVCs. Our main conclusion is that tissue-scale dynamical instabilities caused by RG and enhanced ICa,L give rise to both the trigger and the vulnerable substrate simultaneously for spontaneous initiation of arrhythmias in LQT2 syndrome.
| S-EPMC5206347 | biostudies-literature
Project description:Hutchinson-Gilford progeria syndrome is a rare, segmental premature aging syndrome of accelerated atherosclerosis and early death from myocardial infarction or stroke. This study sought to establish comprehensive characterization of the fatal vasculopathy in Hutchinson-Gilford progeria syndrome and its relevance to normal aging. We performed cardiovascular assessments at a single clinical site on the largest prospectively studied cohort to date. Carotid-femoral pulse wave velocity was dramatically elevated (mean: 13.00±3.83 m/s). Carotid duplex ultrasound echobrightness, assessed in predefined tissue sites as a measure of arterial wall density, was significantly greater than age- and sex-matched controls in the intima-media (P<0.02), near adventitia (P<0.003), and deep adventitia (P<0.01), as was internal carotid artery mean flow velocity (P<0.0001). Ankle-brachial indices were abnormal in 78% of patients. Effective disease treatments may be heralded by normalizing trends of these noninvasive cardiovascular measures. The data demonstrate that, along with peripheral vascular occlusive disease, accelerated vascular stiffening is an early and pervasive mechanism of vascular disease in Hutchinson-Gilford progeria syndrome. There is considerable overlap with cardiovascular changes of normal aging, which reinforces the view that defining mechanisms of cardiovascular disease in Hutchinson-Gilford progeria syndrome provides a unique opportunity to isolate a subset of factors influencing cardiovascular disease in the general aging population.
| S-EPMC3248242 | biostudies-literature
Project description:BackgroundMeasurement of anti-GM1 IgM antibodies in multifocal motor neuropathy (MMN) sera is confounded by relatively low sensitivity that limits clinical usefulness. Combinatorial assay methods, in which antibodies react to heteromeric complexes of two or more glycolipids, are being increasingly applied to this area of diagnostic testing.MethodsA newly developed combinatorial glycoarray able to identify antibodies to 45 different heteromeric glycolipid complexes and their 10 individual glycolipid components was applied to a randomly selected population of 33 MMN cases and 57 normal or disease controls. Comparison with an enzyme-linked immunosorbent assay (ELISA) was conducted for selected single glycolipids and their complexes.ResultsBy ELISA, 22/33 MMN cases had detectable anti-GM1 IgM antibodies, whereas 19/33 MMN samples were positive for anti-GM1 antibodies by glycoarray. Analysis of variance (anova) revealed that of the 55 possible single glycolipids and their 1:1 complexes, antibodies to the GM1:galactocerebroside (GM1:GalC) complex were most significantly associated with MMN, returning 33/33 MMN samples as positive by glycoarray and 29/33 positive by ELISA. Regression analysis revealed a high correlation in absolute values between ELISA and glycoarray. Receiver operator characteristic analysis revealed insignificantly different diagnostic performance between the two methods. However, the glycoarray appeared to offer slightly improved sensitivity by identifying antibodies in four ELISA-negative samples.ConclusionsThe use of combinatorial glycoarray or ELISA increased the diagnostic sensitivity of anti-glycolipid antibody testing in this cohort of MMN cases, without significantly affecting specificity, and may be a useful assay modification for routine clinical screening.
| S-EPMC3896049 | biostudies-literature
Project description:BackgroundAccess to care may be implicated in disparities between men and women in death after acute coronary syndrome, especially among younger adults. We aimed to assess sex-related differences in access to care among patients with premature acute coronary syndrome and to identify clinical and gender-related determinants of access to care.MethodsWe studied 1123 patients (18-55 yr) admitted to hospital for acute coronary syndrome and enrolled in the GENESIS-PRAXY cohort study. Outcome measures were door-to-electrocardiography, door-to-needle and door-to-balloon times, as well as proportions of patients undergoing cardiac catheterization, reperfusion or nonprimary percutaneous coronary intervention. We performed univariable and multivariable logistic regression analyses to identify clinical and gender-related determinants of timely procedures and use of invasive procedures.ResultsWomen were less likely than men to receive care within benchmark times for electrocardiography (≤ 10 min: 29% v. 38%, p = 0.02) or fibrinolysis (≤ 30 min: 32% v. 57%, p = 0.01). Women with ST-segment elevation myocardial infarction (MI) were less likely than men to undergo reperfusion therapy (primary percutaneous coronary intervention or fibrinolysis) (83% v. 91%, p = 0.01), and women with non-ST-segment elevation MI or unstable angina were less likely to undergo nonprimary percutaneous coronary intervention (48% v. 66%, p < 0.001). Clinical determinants of poorer access to care included anxiety, increased number of risk factors and absence of chest pain. Gender-related determinants included feminine traits of personality and responsibility for housework.InterpretationAmong younger adults with acute coronary syndrome, women and men had different access to care. Moreover, fewer than half of men and women with ST-segment elevation MI received timely primary coronary intervention. Our results also highlight that men and women with no chest pain and those with anxiety, several traditional risk factors and feminine personality traits were at particularly increased risk of poorer access to care.
| S-EPMC3986312 | biostudies-literature