Significance of myeloperoxidase plasma levels as a predictor for cardiac resynchronization therapy response.

OBJECTIVES: This study aimed to determine if changes in myeloperoxidase (MPO) levels correlate with response to cardiac resynchronization therapy (CRT) and the potential role of MPO as a predictor of response to CRT. BACKGROUND: CRT is a well-established treatment option in chronic heart failure (CHF) with 50-80% of patients benefiting. Inflammation and oxidative stress play a key role in CHF pathophysiology. Previous studies have demonstrated increased levels of MPO in CHF patients, but the correlation with CRT response remains incompletely understood. METHODS: Fifty-three patients underwent CRT implantation. During follow-up, patients were divided into two groups, responders and non-responders to CRT, based on improved physical capacity and NYHA classification. Levels of MPO and NT-pro-brain-natriuretic-peptide (NT-proBNP) were determined prior to implantation, 30 and 90 days after. Physical capacity, including a 6-min walking-test, NYHA class, and LVEF were evaluated at baseline and during follow-up. RESULTS: Thirty-four patients (64%) responded to CRT, showing improved physical capacity and LVEF. All responders revealed a significant decrease of MPO levels (503.8 ng/ml vs. 188.4 ng/ml; p < 0.001). Non-responding patients did not show any significant changes in clinical parameters or MPO levels (119.6 ng/ml vs. 134.3 ng/ml; p = 0.672) during follow-up. At baseline, physical capacity and NYHA class, as well as MPO levels differed significantly between both groups (p < 0.001). A ROC analysis identified an MPO cut-off value for response to CRT of 242 ng/ml with a sensitivity of 93.5% and specificity of 71.4%. There was a strong correlation between MPO and improvement of LVEF (Spearman's rho: - 0.453; p = 0.005) and physical capacity (Spearman's rho: - 0.335; p = 0.042). CONCLUSIONS: Response to CRT and course of MPO levels correlate significantly. MPO levels differ between responders and non-responders prior to CRT, which may indicate an additional value of MPO as a predictor for CRT response. Further randomized studies are required to confirm our data in larger patient cohorts.

Shedding of the endothelial glycocalyx is quantitatively proportional to burn injury severity.

Limited information exists regarding endothelial dysfunction following burn injury. This project aims to evaluate whether thermal injury results in shedding of the endothelial glycocalyx in a manner quantitatively proportional to injury severity, and whether theloss of intact glycocalyx is measurable in end organs. C57BL/6 mice were grouped as uninjured controls, 10% or 25% Total Body Surface Area (TBSA) scald burns. Blood and tissue sampling was performed over a specific time course. Plasma levels of shed syndecan-1, a marker of glycocalyx damage, were quantified by ELISA. Lung and spleen sections were stained with immunofluorescent anti-syndecan-1 antibodies to evaluate intact glycocalyx. Plasma syndecan-1 levels were higher in injured versus uninjured animals. Normalized levels of syndecan-1 in burned mice were significantly increased compared to hour 0 (p<0.05) at hours 4 and 8 post-injury in the 10% TBSA, and at hour 4 in the 25% TBSA group. Levels in the 10% and 25% TBSA groups peaked at hour 4 with fold change of 2.3 and 2.4 respectively. There was less pulmonary syndecan-1 immunostaining in burned animals compared to controls, and the levels inversely correlated with systemic shed syndecan- 1, beginning at hour 4 in the 10% TBSA injury group and at all time points in the 25% TBSA injury group, (0.27±0.06 and 0.14±0.04 respectively for hour 4). Similarly, there was less spleen syndecan-1 immunostaining in burned animals compared to controls at all time points. Burn injury causes shedding of syndecan-1 in a murine model, with levels correlated to injury severity and loss of the glycocalyx in lung and spleen. This work provides further insight into quantification and temporality of glycocalyx damage and systemic response to burn.

Les données concernant la dysfonction endothéliale après brûlure sont parcellaires. Les buts de cette étude étaient d'établir une corrélation entre la perte de glycocalyx et la gravité de la brûlure et si cette perte était mesurable au niveau des organes. Des souris C57BL/6 ont été réparties en groupes contrôle, brûlure 10% et brûlure 25% de SCT. Des prélèvements de sang et de tissus ont été réalisés à intervalles prédéterminés. Les taux plasmatiques de syndecan 1 (S1), marqueur de lésion du glycocalyx, ont été mesuré par méthode ELISA. Des échantillons de poumon et de rate ont été mis en présence d'anticorps anti S1, afin d'évaluer le glycocalyx intact. Les taux plasmatiques de S1 étaient plus élevés que ceux du groupe contrôle. Chez les souris brûlées sur 10% de SCT, les taux de S1 à 4h et 8 h étaient supérieurs au taux avant brûlure, ceci n'étant observé qu'à h4 chez les souris brûlées sur 25% de SCT. Le pic de S1 se produisait à h4, avec un rapport de x2,3 (10%) et x2,4 (25%) par rapport à la valeur de base. A partir de h4, on observait une baisse de complexes S1-antiS1 dans les poumons des souris brûlées sur 10% (0,27 +/- 0,06), inversement corrélée aux taux plasmatiques de S1. Cette observation se répétait lors de tous les dosages chez les 25% (0,14 +/- 0,04 à h4). Les mêmes constatations étaient faites sur les échantillons de rate. La brûlure cause des lésions du glycocalyx, parallèles à sa gravité. Ces travaux ouvrent le champ à des recherches futures sur les lésions du glycocalyx et la réponse inflammatoire aux brûlures.

Electrical cardioversion of patients with implanted pacemaker or cardioverter-defibrillator: results of a survey of german centers and systematic review of the literature.

AIMS: A relevant number of patients presenting for electrical cardioversion carry a pacemaker (PM) or ICD. Case reports suggest a potential hazard of external cardioversion/defibrillation. The incidence of shock related device complications is unknown. No guidelines or recommendations by international medical societies for a cardioversion protocol of cardiovascular implantable electronic device (CIED) patients exist. We conducted a nationwide survey to gather real-world clinical data on the current clinical approach towards these patients during electrical cardioversion and to estimate the incidence of shock-related complications. METHODS AND RESULTS: Ninety hospitals with > 380 ECV in 2014 were identified from mandatory hospital quality reports and 60 were randomly selected. All centers were provided with a standardized questionnaire on the general proceedings and complications during electrical cardioversion of pacemaker, ICD and CRT patients (CIED patients). Thirty-two centers (53%) participated in the survey. In total, 16,554 ECV were reported (534 ± 314 per center). Biphasic cardioversion with a first shock energy of ≥ 150 J via adhesive patches in antero-posterior orientation was preferred by most centers (78%). Eleven percent (n = 1809) of pts were reported to carry a PM/ICD. The ECV protocol was heterogeneous among centers. Complications associated with electrical cardioversion were reported in 11/1809 patients (0.6%), all were transitory elevations of pacing thresholds. CONCLUSIONS: In this nationwide snapshot survey of cardioversion procedures in Germany, approximately 11% of patients presenting for elective electrical cardioversion were pacemaker or ICD carriers. Cardioversion protocols in these patients are heterogeneous throughout centers and mostly not in accordance with recommendation of the German Cardiac Society. Complications associated with external electrical cardioversion are rare. Controlled trials and large registries are necessary to provide evidence for future recommendations.

External electrical cardioversion of persistent atrial fibrillation in a patient with a Micra™ Transcatheter Pacing System.

We report a case of a 85-year old woman with a preexisting Transcatheter Pacing System (TPS) (Micra™ VR, Fa. Medtronic, Inc., Minneapolis, MN, USA) undergoing several external electrical cardioversions (CV) for symptomatic persistent atrial fibrillation (persAF). Due to bradycardia in the setting of atrial fibrillation a right apical TPS implantation was performed earlier. Four weeks prior to presentation at our facility an unsuccessful CV with a maximum biphasic energy level of 360J was performed, after which amiodarone was initiated. At the time of presentation three shocks with 100 J, 200 J and 360 J were delivered without sustained restoration of a stable sinus rhythm. Patches were in an anterior-posterior position. No complications and no significant changes in device parameters in comparison to the pre-acquired values were observed. To our knowledge, this is the first case report of an external CV in a patient with a TPS. External CV in patients with a preexisting TPS seems to be safe and feasible.

Predictors of Atrial Fibrillation Recurrence after Catheter Ablation: Data from the German Ablation Registry.

Catheter ablation (CA) for atrial fibrillation (AF) has emerged as a widespread first or second line treatment option. However, up to 45% of patients (pts) show recurrence of AF within 12 month after CA. We present prospective multicenter registry data comparing characteristics of pts with and without recurrence of AF within the first year after CA. This study comprises all pts with complete follow-up one year after CA (1-y-FU; n = 3679). During 1y-FU in 1687 (45.9%) pts recurrence of AF occurred. The multivariate analysis revealed female sex and AF type prior to the procedure as predictors for AF recurrence. Furthermore, comorbidities such as valvular heart disease and renal failure as well as an early AF relapse were also predictors of AF recurrence during 1-y-FU. However, despite an AF recurrence rate of 45.9%, the majority of these pts (72.4%) reported a significant alleviation of clinical symptoms. In conclusion in pts with initially successful CA for AF female sex, AF type, in-hospital AF relapse and comorbidities such as renal failure and valvular heart disease are independent predictors for AF recurrence during 1-y-FU. However, the majority of pts deemed their interventions as successful with significant reduction of symptoms irrespective of AF.

[Catheter ablation and the complications]. / Katheterablation und die Komplikationen.

Catheter ablation of atrial fibrillation has developed into a standard therapy and even in some cases as a first line therapy. This has resulted in a clear increase in the number of procedures in recent years. The published data from experienced centers indicate that the number of complications decreases with increasing experience; however, due to the parallel increase in the number of inexperienced centers, the average complication rate shows a tendency to increase. In the long term this necessitates a reliable quality assurance in order not to leave the choice of the "safe centers" up to the patient. Vascular complications are the most common, which in most cases have an uneventful course and do not necessitate further interventions. Particularly the incidence of ischemic stroke can be well-countered by strict control of periprocedural anticoagulation. The frequency of occurrence of phrenic nerve lesions, which are more common when selecting cryoenergy, can be reduced by stimulation of the phrenic nerve during ablation of the right pulmonary vein. The most feared complication of an atrioesophageal fistula is rare. No data for an effective avoidance of complications are available. A postprocedural therapy with proton pump inhibitors for 4-6 weeks, the intraprocedural measurement of esophageal temperature and reduction of the ablation energy on the posterior wall of the left atrium can possible help to reduce the frequency of complications.

[Interventional treatment for paroxysmal atrial fibrillation : which is the optimal ablation approach?]. / Interventionelle Therapie von paroxysmalem Vorhofflimmern : Welche ist die beste Ablationsstrategie?

Atrial fibrillation is one of the most common arrhythmias and effects probably more than 35 million people worldwide. The incidence in patients older than 70 years of age is as high as 10%. One can expect that according to our demographic development this entity will be increasingly important within the next years and decades. Along with the well know and established but at the same time limited opportunities of pharmacological treatment option of this arrhythmia, catheter ablation has evolved as a safe and effective treatment option. Electrical isolation of the pulmonary vein remains the standard of care and results in success rates as high as 80% using modern ablation strategies. Optimization of procedural and ablation techniques has lead to this high success rates. Different energy sources are available, such as radiofrequency, cryoenergy and laser are widely used today to treat patients with symptomatic atrial fibrillation. PV isolation using a so called "single-shot" ablation approach has shown to be effective with a reduced requirement of periprocedural resources and therefore resulting in wider application of this treatment not only in specialized electrophysiological centers. The rapid development in this field leads to the question which approach can be used as the most likely to result in the highest success and least complication rates. This question will be addressed in the following manuscript.

[Ablation of an idiopathic "ventricular rarity"--ventricular tachycardia originating from the crux cordis]. / Ablation eines idiopathischen "ventrikulären Kolibris"--ventrikuläre Tachykardien aus der Crux cordis.

HISTORY AND ADMISSION FINDINGS: A 62-year-old woman presented with history of repeat syncope and palpitations. She experienced aggravation of symptoms within the last few months. At referring hospital a ventricular tachycardia was already inducible during electrophysiological study. The patient was transferred to our hospital for VT ablation vs. ICD implantation. INVESTIGATION: No evidence for structural heart disease was revealed during TTE nor was a coronary heart disease detectable during coronary angiography, only hypertension was verifiable. No ICD implantation so far. TREATMENT AND COURSE: The patient underwent repeat EP study at our facility with induction of VT. Pace-mapping and mapping for earliest ventricular activation was performed. The middle-cardiac vein was revealed as site of earliest ventricular activation (50 ms) and good pace-map. Therefore, radiofrequency ablation at this site terminated successfully VT into sinus rhythm. CONCLUSION: Ablation of epicardial VT foci is successfully feasible via coronary sinus. With regard to typical ECG parameters an epicardial foci may be assumed precociously. The great cardiac vein is one of the most common sites of origin for epicardial foci, however, VT partially may originate from the crux cordis which is accessible for ablation via the middle cardiac vein with good ablation results.

Acute lymphoblastic leukaemia: an unusual radiological presentation.

A 14-year-old female patient attended Bristol Dental Hospital for an oral screening prior to undergoing a bone marrow transplant as treatment for her acute lymphoblastic leukaemia. Maxillofacial radiographs revealed multiple, well-defined, non-corticated radiolucent lesions throughout the vault of her skull and mandible. These radiological features (coupled with the patient's age) would have correlated with a diagnosis of Langerhans cell histiocytosis. However, a previous bone marrow biopsy confirmed that the patient did indeed have acute lymphoblastic leukaemia. The lytic lesions were present throughout her entire skeletal frame and had previously led to episodes of leg and abdominal pain. We feel that this radiological presentation of leukaemia needs to be reported as these features could easily have been confused with other haematological or even malignant conditions.

A study of the clinical characteristics of benign trigeminal sensory neuropathy.

PURPOSE: The purpose of this study was to describe the clinical characteristics of a series of patients presenting with benign trigeminal sensory neuropathy. PATIENTS AND METHODS: We conducted a retrospective analysis of the clinical and pathologic characteristics of 23 patients presenting with facial numbness of unknown etiology. RESULTS: Patients presented with diverse medical histories but could be grouped into those with a connective tissue disorder, neurologic disease, psychologic problems, or a medical history of unknown significance. The age of the patient, the severity and distribution of the trigeminal neuropathy, and symptoms other than neuropathy closely reflected the patient's medical history. The majority of patients underwent magnetic resonance imaging, but the results did not facilitate the diagnosis of the condition or reflect the extent and severity of the symptoms. In 60% of patients, the symptoms remained unchanged during the course of the study and outcome was not influenced by medical treatment. CONCLUSIONS: The diagnosis and management of benign trigeminal sensory neuropathy remain a significant clinical challenge.

Holes in the head: parietal foramina, a developmental anomaly seen during a routine orthodontic assessment.

Parietal foramina (Catlin marks) are developmental anomalies which affect approximately 1 in 25,000 people. They are thought to be inherited as an autosomal trait and may be associated with other skeletal anomalies such as cleft lip or palate. The majority of enlarged parietal foramina are usually completely asymptomatic.

Demographics of HIV-infected persons attending a dental clinic.

The demographics of 147 HIV-infected persons attending a special care dental clinic in South West England are reported. The majority of attendants were homosexual/bisexual males, reflecting the UK epidemiology of HIV disease at the time of study. There was a substantial rise in patient numbers from 1988 onwards but patients often did not reveal their route of HIV acquisition or increasingly had acquired HIV disease via heterosexual routes. Patients were usually referred for routine dental treatment, not HIV-related oral disease. The HIV-infected patients generally attended the clinic irregularly, despite being offered many appointments. It is concluded that most patients with HIV disease attend clinics for routine dental care, yet many may be unable or unwilling to attend regularly.

Emergence of azole drug resistance in Candida species from HIV-infected patients receiving prolonged fluconazole therapy for oral candidosis.

We examined the effect of different fluconazole treatment regimens on the emergence of azole drug resistance among Candida species recovered from the mouths of 54 HIV-infected individuals. Patients were assigned to one of three treatment groups depending on their history of oral candidosis and fluconazole use. Mouthwashes obtained at regular intervals were cultured and isolates identified using standard methods. Antifungal broth micro-dilution tests were performed to determine IC30s of fluconazole and ketoconazole. Sixty-four Candida albicans isolates from 20 patients with no evidence of oral candidosis who had not received fluconazole all had IC30s of < or = 4 mg/L. Thirty-four (83%) of 41 C. albicans isolates from ten patients receiving intermittent, short-term fluconazole treatment for oral candidosis had IC30s of < or = 4 mg/L, but only two isolates (5%) had IC30s > or = 64 mg/L. In contrast, 26 (40%) of 65 C. albicans isolates from 15 patients given long-term fluconazole (50-200 mg/day or 150 mg/week) were classified as resistant having IC30s of fluconazole of > or = 64 mg/L. Ten of these 26 fluconazole-resistant isolates were susceptible to ketoconazole with IC30s of < or = 4 mg/L suggesting azole drug cross-resistance is not inevitable. Tests on multiple colonies from individual isolation plates showed that it was not unusual to obtain differing IC30 values, indicating that a sweep inoculum is essential if resistance is to be detected. Nine (60%) of the 15 patients given long-term fluconazole harboured isolates of C. albicans that were resistant to fluconazole at some time during the study period. All had low CD4 counts and were approaching the final stage of their illness. Three patients on long-term treatment had resistant organisms at the outset of the study; in the remainder, resistant strains emerged during the study period. In six of the nine cases, emergence of resistance in vitro correlated with persistent clinical signs of oral infection. Thirty-six isolates of Candida species other than C. albicans were also recovered from patients receiving long-term fluconazole and 29 (81%) of these had IC30s of > or = 64 mg/L. Our experience with C. albicans in patients with HIV infection, suggests that the long-term azole drug use may be an important factor in the development of fluconazole resistance as such resistance was rare and transient in patients on intermittent short-term treatment.

Oral features of a family with benign familial neutropenia.

The oral features of three members of a family with familial benign neutropenia (a mother and two children) are detailed. Prepubertal periodontitis, oral ulceration, and angular stomatitis were the principal features.

HIV-salivary gland disease. Salivary scintiscanning with technetium pertechnetate.

The salivary disease in two patients with human immunodeficiency virus infection was investigated by technetium pertechnetate scintiscanning. Although there was good histologic evidence of benign lymphoepithelial disease, scintiscanning failed to delineate any salivary lesions. Technetium pertechnetate scintiscanning seems to be of little value in the detailed investigation of salivary disease in human immunodeficiency virus infection, though gallium scanning can help. Fine needle aspiration or biopsy remain the main diagnostic tools.