Shortening of the Short Refractory Periods in Short QT Syndrome.

BACKGROUND: Diagnosis of short QT syndrome (SQTS) remains difficult in case of borderline QT values as often found in normal populations. Whether some shortening of refractory periods (RP) may help in differentiating SQTS from normal subjects is unknown. METHODS AND RESULTS: Atrial and right ventricular RP at the apex and right ventricular outflow tract as determined during standard electrophysiological study were compared between 16 SQTS patients (QTc 324±24 ms) and 15 controls with similar clinical characteristics (QTc 417±32 ms). Atrial RP were significantly shorter in SQTS compared with controls at 600- and 500-ms basic cycle lengths. Baseline ventricular RP were significantly shorter in SQTS patients than in controls, both at the apex and right ventricular outflow tract and for any cycle length. Differences remained significant for RP of any subsequent extrastimulus at any cycle length and any pacing site. A cut-off value of baseline RP <200 ms at the right ventricular outflow tract either at 600- or 500-ms cycle length had a sensitivity of 86% and a specificity of 100% for the diagnosis of SQTS. CONCLUSIONS: Patients with SQTS have shorter ventricular RP than controls, both at baseline during various cycle lengths and after premature extrastimuli. A cut-off value of 200 ms at the right ventricular outflow tract during 600- and 500-ms basic cycle length may help in detecting true SQTS from normal subjects with borderline QT values

Etiological diagnosis, prognostic significance and role of electrophysiological study in patients with Brugada ECG and syncope.

BACKGROUND: Syncope is considered a risk factor for life-threatening arrhythmias in Brugada patients. Distinguishing a benign syncope from one due to ventricular arrhythmias is often difficult, unless an ECG is recorded during the episode. Aim of the study was to analyze the characteristics of syncopal episodes in a large population of Brugada patients and evaluate the role of electrophysiological study (EPS) and the prognosis in the different subgroups. METHODS AND RESULTS: One hundred ninety-five Brugada patients with history of syncope were considered. Syncope were classified as neurally mediated (group 1, 61%) or unexplained (group 2, 39%) on the basis of personal and family history, clinical features, triggers, situations, associated signs, concomitant therapy. Most patients underwent EPS; they received ICD or implantable loop-recorder on the basis of the result of investigations and physician's judgment. At 62±45months of mean follow-up, group 1 showed a significantly lower incidence of arrhythmic events (2%) as compared to group 2 (9%, p<0.001). Group 2 patients with positive EPS showed the highest risk of arrhythmic events (27%). No ventricular events occurred in subjects with negative EPS. CONCLUSION: Etiological definition of syncope in Brugada patients is important, as it allows identifying two groups with different outcome. Patients with unexplained syncope and ventricular fibrillation induced at EPS have the highest risk of arrhythmic events. Patients presenting with neurally mediated syncope showed a prognosis similar to that of the asymptomatic and the role of EPS in this group is unproven

Quantitative Assessment of Cancer Vascular Architecture by Skeletonization of High-resolution 3-D Contrast-enhanced Ultrasound Images: Role of Liposomes and Microbubbles.

The accurate characterization and description of the vascular network of a cancer lesion is of paramount importance in clinical practice and cancer research in order to improve diagnostic accuracy or to assess the effectiveness of a treatment. The aim of this study was to show the effectiveness of liposomes as an ultrasound contrast agent to describe the 3-D vascular architecture of a tumor. Eight C57BL/6 mice grafted with syngeneic B16-F10 murine melanoma cells were injected with a bolus of 1,2-Distearoyl-sn-glycero-3-phosphocoline (DSPC)-based non-targeted liposomes and with a bolus of microbubbles. 3-D contrast-enhanced images of the tumor lesions were acquired in three conditions: pre-contrast, after the injection of micro bubbles, and after the injection of liposomes. By using a previously developed reconstruction and characterization image processing technique, we obtained the 3-D representation of the vascular architecture in these three conditions. Six descriptive parameters of these networks were also computed: the number of vascular trees (NT), the vascular density (VD), the number of branches, the 2-D curvature measure, the number of vascular flexes of the vessels, and the 3-D curvature. Results showed that all the vascular descriptors obtained by liposome-based images were statistically equal to those obtained by using microbubbles, except the VD which was found to be lower for liposome images. All the six descriptors computed in pre-contrast conditions had values that were statistically lower than those computed in presence of contrast, both for liposomes and microbubbles. Liposomes have already been used in cancer therapy for the selective ultrasound-mediated delivery of drugs. This work demonstrated their effectiveness also as vascular diagnostic contrast agents, therefore proving that liposomes can be used as efficient “theranostic” (i.e. therapeutic 1 diagnostic) ultrasound probes

In vivo magnetic resonance spectroscopy in the brain of Cdkl5 null mice reveals a metabolic profile indicative of mitochondrial dysfunctions

Mutations in the X‐linked CDKL5 gene cause CDKL5 deficiency disorder (CDD), a severe neurodevelopmental condition mainly characterized by infantile epileptic encephalopathy, intellectual disability, and autistic features. The molecular mechanisms underlying the clinical symptoms remain largely unknown and the identification of reliable biomarkers in animal models will certainly contribute to increase our comprehension of CDD as well as to assess the efficacy of therapeutic strategies. Here, we used different Magnetic Resonance (MR) methods to disclose structural, functional, or metabolic signatures of Cdkl5 deficiency in the brain of adult mice. We found that loss of Cdkl5 does not cause cerebral atrophy but affects distinct brain areas, particularly the hippocampus. By in vivo proton‐MR spectroscopy (MRS), we revealed in the Cdkl5 null brain a metabolic dysregulation indicative of mitochondrial dysfunctions. Accordingly, we unveiled a significant reduction in ATP levels and a decrease in the expression of complex IV of mitochondrial electron transport chain. Conversely, the number of mitochondria appeared preserved. Importantly, we reported a significant defect in the activation of one of the major regulators of cellular energy balance, the adenosine monophosphate‐activated protein kinase (AMPK), that might contribute to the observed metabolic impairment and become an interesting therapeutic target for future preclinical trials. In conclusion, MRS revealed in the Cdkl5 null brain the presence of a metabolic dysregulation suggestive of a mitochondrial dysfunction that permitted to foster our comprehension of Cdkl5 deficiency and brought our interest towards targeting mitochondria as therapeutic strategy for CDD

Incessant pericarditis as a risk factor for complicated pericarditis and hospital admission

Abstract Background Incessant pericarditis is defined as pericarditis with persistent symptoms without a symptom-free interval of 4 to 6 weeks despite therapy. On the contrary, recurrent pericarditis is characterized by recurring symptoms after a symptom-free interval of at least 4 to 6 weeks, allowing the completion of therapy. Aims The aim of this study is to assess the risk of complicated pericarditis and related hospitalizations according to the clinical pattern of incessant or recurrent pericarditis. Methods From January 2017 to December 2018, all consecutive patients admitted to AOU Città della Salute (Turin, IT) for pericarditis were included in a prospective cohort study with a clinical and echocardiographic follow-up at 1, 3, and 6 months, and then every 6 months. Results We included 147 patients (median age, 50.9 years [IQR, 28.5]; 49.7% women, 89% had idiopathic aetiology, 11% had pericarditis related to systemic inflammatory disease/postcardiac injury syndrome, 80% had pericardial effusion, and 62% had elevated C-reactive protein &gt;5 mg/L). Patients were treated according to ESC guidelines. After a median follow-up of 14 months (IQR, 9 months), adverse events were recorded in 54/147 patients (36.7%): nonidiopathic/viral aetiology in 16 of 147 cases (10.9%), recurrent pericarditis/persistent symptoms in 53 of 147 cases (36.1%), cardiac tamponade in 4/147 cases (2.7%), persistent CP in 4/147 cases (2.7%), and hospitalization related to pericarditis in 38/147 cases (25.9%). An incessant course was reported in 18 of 147 cases (12%). The risk of complications was higher in patients with incessant pericarditis (Figure) – especially CP – compared to nonincessant course (22.2% versus 0%, respectively; P&lt;0.001). Patients with incessant pericarditis more commonly had echocardiographic evidence of CP (77.8% vs. 9.3%; P&lt;0.001) and thickened pericardium on multimodality imaging (66.7% vs. 4.7%; P&lt;0.001). These findings were reversible with medical therapy with the use of anakinra (100 mg/d) and colchicine in all but 4 cases that progressed to persistent CP, which were referred for pericardiectomy. An analysis of risk factors for complicated pericarditis and hospitalization using Cox proportional hazards regression analysis identified the following risk factors: large pericardial effusion (hazard ratio, 7.63 [95% CI, 3.09–18.83]), elevated C-reactive protein &gt;5 mg/L (hazard ratio, 5.55 [95% CI, 1.87–16.44]), and incessant course (HR, 17.10 [95% CI, 7.63–38.33]). Conclusions This study highlights that an incessant course of pericarditis is a possible new risk factor for complications and especially for developing constriction. In clinical practice, the detection of an incessant course, as well as imaging findings of constriction and pericardial thickening, should prompt more diagnostic testing, a close follow-up, and more aggressive therapy to prevent complications and persistent constriction. Funding Acknowledgement Type of funding sources: None. Figure