Characterization of onset mechanism and waveform analysis in patients with atrial fibrillation using a high-resolution noncontact mapping system

INTRODUCTION: Information on the spatiotemporal organization of atrial activity at the onset of atrial fibrillation (AF) is limited. METHODS AND RESULTS: The study consisted of 26 consecutive patients (22 men and 4 women; mean age 56 +/- 9 years) with AF in whom the left atrium (LA) was mapped using a noncontact mapping system. At the onset of AF, the AF cycle lengths and wavefronts were analyzed at the site of origin of the triggering atrial premature complex (APC) and five predefined sites within the LA (superior, anterior, posterior, lateral, and septal walls). If repetitive activity was observed at the site of origin of APCs, triggered AF episodes were considered as focally driven. APCs that induced AF had shorter coupling intervals than APCs that did not induce AF (300 +/- 41 msec vs 392 +/- 64 msec, P < 0.001). Immediately after AF onset, repetitive firing was crucial for maintenance of arrhythmia in 52 (80%) of 65 AF episodes. In 13 AF onset episodes (20%), AF was maintained by other mechanisms. The number of LA wavefronts after AF onset was lower in focally driven AF episodes compared with episodes in which no focally driven activity was observed (1.9 +/- 0.6 v. 2.3 +/- 2.3 wavefronts, P < 0.05). After the onset of AF, the posterior wall of the LA showed the earliest disorganized activity (after 5.2 +/- 3.1 cycles). CONCLUSION: In the majority of AF episodes (80%), repetitive firing from the triggering foci may play an important role in maintaining AF immediately after arrhythmia onset. In 20% of the episodes, AF at early stages seems to be maintained by other mechanisms. The capability of APCs to induce AF depends on the coupling interval and the focus localization. The posterior wall of the LA shows the earliest disorganization of wavefronts at the onset of AF.     

Outcome and prognostic factors of multimodal therapy for pulmonary large-cell neuroendocrine carcinomas

Background

There is controversy whether patients diagnosed with large-cell neuroendocrine carcinoma (LCNEC) should be treated according to protocols for non-small cell lung cancers (NSCLC) or small cell lung cancers (SCLC), especially with regard to the administration of prophylactic cranial irradiation (PCI). This study was set up to determine the incidence of brain metastases and to investigate the outcome following multimodal treatment in 70 patients with LCNEC.

Methods

Seventy patients with histologically confirmed LCNEC were treated at the University Hospital of Heidelberg between 2001 and 2014. Data were collected retrospectively. Al most all patients received thoracic surgery as initial treatment (94 %). Chemotherapy was administered in 32 patients as part of the initial treatment. Fourteen patients were treated with adjuvant or definitive thoracic radiotherapy according to NSCLC protocols. Cranial radiotherapy due to brain metastases, mostly given as whole brain radiotherapy (WBRT), was received by fourteen patients. Statistical analysis was performed using the long-rank test and the Kaplan–Meier method.

Results

Without PCI, the detected rate for brain metastases was 25 % after a median follow-up time of 23.4 months, which is comparable to NSCLC patients in general. Overall (OS), local (LPFS), brain metastases-free survival (BMFS) and extracranial distant progression-free survival (eDPFS) was 43, 50, 63 and 50 % at 5 years, respectively. Patients with incomplete resection showed a survival benefit from adjuvant radiotherapy. The administration of adjuvant chemotherapy improved the general worse prognosis in higher pathologic stages.

Conclusion

In LCNEC patients, the administration of radiotherapy according to NSCLC guidelines appears reasonable and contributes to acceptable results of multimodal treatment regimes. The low incidence of spontaneous brain metastases questions a possible role of PCI.     

Effect of chronic alcohol consumption on the development and progression of non-alcoholic fatty liver disease (NAFLD)

A number of epidemiologic studies show a protective effect of light to moderate daily alcohol consumption on the development of non-alcoholic fatty liver disease (NAFLD). Although these small amounts of ethanol may prevent fatty liver, they may also be a risk factor for other diseases such as breast and colon cancer. Those individuals who have underlying hepatic steatosis or non-alcoholic steatohepatitis (NASH) should not use ethanol chronically since the data available at present do not support a beneficial effect of alcohol in this situation. Especially overweight and obese individuals may be more susceptible towards alcohol even at moderate doses. Animal experiments show a negative effect of ethanol on liver histology in either dietary or genetic NASH models. In addition, patients with NASH reveal a significant increased risk for hepatocellular cancer (HCC) even with social alcohol consumption. Thus, subjects with underlying NASH should abstain from alcohol at any amounts.     

Do we understand who benefits from resynchronisation therapy?

This editorial refers to "Interventricular and intraventriculardyssynchrony are common in heart failure patients, regardlessof QRS duration"¹ by S. Ghio et al. on page 571 Interest in ventricular dyssynchrony in heart failure patientshas been renewed recently by the introduction of cardiac resynchronisationtherapy (CRT). CRT is currently accepted as an adjunct to themedical treatment of symptomatic heart failure in patients withsevere left ventricular systolic dysfunction and ECG manifestationsof ventricular conduction delay.¹ It aims to reduce the electricalconduction delay by pre-excitation of late-activated regionswith left- or biventricular pacing to restore a more synchronouscontraction pattern. Although this strategy has been provento be effective at group     

Serum insulin and plasma glucagon in human pregnancy — On the pathogenesis of gestational diabetes. A review

Summary The possibility that the deterioration of glucose tolerance during pregnancy might be due to a change in the functional condition of the endocrine pancreas has been examined in normal pregnant women and in non-obese gestational diabetics. Three test-situations were applied to elucidate the problem: 1) an overnight fast; 2) a glucose tolerance test (OGTT); and 3) a protein-rich meal. After the overnight fast, hyperinsulinemia and hyperglucagonemia were found in late pregnancy in both groups. However, on a molar basis, basal insulin increased more than basal glucagon and the molar insulin: glucagon ratio was therefore increased. After oral administration of glucose, the insulin response was enhanced in the late stages of pregnancy both in normal women and in those with gestational diabetes while the depression of glucagon below fasting levels was exaggerated and sustained in both groups. In response to a protein-rich meal in normal late pregnancy, the glucagon response was significantly lower than post partum in the same subjects, whereas that of insulin was unchanged. Finally, in both groups the diminished glucose tolerance in pregnancy was not associated with an abnormally elevated proportion of total insulin immunoreactivity represented by the biologically almost inactive proinsulin. Based upon these findings and those reported in the literature, it is concluded that there is no evidence in support of the idea that the diabetogenicity of pregnancy can be explained by changes in the function of the endocrine pancreas in these patients.     

Does tumour necrosis factor‐α inhibitor infliximab induce histological resolution of pulmonary sarcoid granulomas?

Background: Sarcoid granuloma formation involves the orchestration of cytokines and chemokines, which modulate the host's immune response to the antigen stimulus. The release of cytokines enhances expression of the pro‐inflammatory cytokine tumour necrosis factor‐α (TNF), which plays a crucial role in the formation of sarcoid granuloma, being released from T‐lymphocytes and alveolar macrophages. Objective: The aim of this study was to evaluate the effect of infliximab in a case of pulmonary sarcoidosis using a histological approach. Materials and Methods: A 44‐year‐old man with biopsy verified chronic pulmonary sarcoidosis being resistant to treatment with corticosteroids and cell cycle inhibitors. Persisting disease activity was confirmed by declining lung function tests and a positive fluorine‐18‐fluorodeoxyglucose–positron emission tomography scan. The patient was treated with a single course of infliximab 3‐mg/kg body weight; 11 days later, a single lung transplantation was performed. Immunohistological staining with the macrophage marker CD68 was performed on lung tissue and mediastinal lymph node tissue from both the initial diagnostic evaluation (prior to infliximab) as well as from the explanted lung (after infliximab). Results: Biopsy specimens from lung and mediastinal lymph nodes prior to infliximab demonstrated sarcoid granulomas, and staining with CD68 showed dense infiltration by macrophages (epithelioid cells) in the central part of the granulomas. In contrast, biopsies from the explanted lung after infliximab demonstrated acellular sarcoid granulomas with central amorphous masses, and staining with CD68 showed complete absence of macrophages. Conclusions: In this patient, the TNF inhibitor infliximab appeared to induce resolution of sarcoid granulomas starting with disappearance of macrophages probably caused by cell lysis or apoptosis. Please cite this paper as: Milman N, Andersen CB, Baslund B, Loft A and Iversen M. Does tumour necrosis factor‐α inhibitor infliximab induce histological resolution of pulmonary sarcoid granulomas? The Clinical Respiratory Journal 2007; 1:106–113.     

Acute effects and long-term outcome of pulmonary vein isolation in combination with electrogram-guided substrate ablation for persistent atrial fibrillation

Complex fractionated atrial electrographic (CFAE) catheter ablation is a new approach for the treatment of atrial fibrillation (AF). It is unclear if acute results of this approach correspond to long-term outcome. The purpose of this study was to prospectively assess acute and long-term successes of an ablation approach combining pulmonary vein isolation (PVI) and ablation of CFAE areas for treatment of persistent AF. PVI and ablation of CFAE areas were performed in 35 patients with persistent AF (30 men, 57+/-9 years of age). At the end of the ablation procedure AF had terminated in 23 of 35 patients (66%) by conversion to sinus rhythm (8 of 23 patients, 35%) or organization to atrial tachycardia (15 of 23 patients, 65%). AF persisted in 12 of 35 patients (34%). At the end of the follow-up period (19+/-12 months), sinus rhythm was present in 26 of 35 patients (74%), including 9 patients with a repeat procedure. This group of 26 patients consisted of 7 of 8 patients (88%) with acute sinus rhythm after the first ablation, 11 of 15 patients (73%) with organization, and 8 of 12 patients (66%) with ongoing AF (p=0.32). In conclusion, a combined approach of PVI and CFAE ablation in persistent AF leads to acute AF termination in 66% and long-term maintenance of sinus rhythm in 74% of cases. However, long-term outcome was not predictable by acute results of the ablation procedure.