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In a randomized trial, 398 patients with heart failure and atrial fibrillation were assigned to either catheter ablation or medical therapy. Catheter ablation significantly reduced the primary outcome of death from any cause or hospitalization for worsening heart failure.

AimsIn the IN-TIME trial, automatic daily implant-based multiparameter telemonitoring significantly improved clinical outcomes in patients with chronic systolic heart failure and implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D). We compared IN-TIME results for ICD and CRT-D subgroups.MethodsPatients with LVEF ≤ 35%, NYHA class II/III, optimized drug treatment, no permanent atrial fibrillation, and a dual-chamber ICD (n = 274) or CRT-D (n = 390) were randomized 1:1 to telemonitoring or no telemonitoring for 12 months. Primary outcome measure was a composite clinical score, classified as worsened if the patient died or had heart failure-related hospitalization, worse NYHA class, or a worse self-reported overall condition.ResultsThe prevalence of worsened score at study end was higher in CRT-D than ICD patients (26.4% vs. 18.2%; P = 0.014), as was mortality (7.4% vs. 4.1%; P = 0.069). With telemonitoring, odds ratios (OR) for worsened score and hazard ratios (HR) for mortality were similar in the ICD [OR = 0.55 (P = 0.058), HR = 0.39 (P = 0.17)] and CRT-D [OR = 0.68 (P = 0.10), HR = 0.35 (P = 0.018)] subgroups (insignificant interaction, P = 0.58–0.91).ConclusionDaily multiparameter telemonitoring has a potential to reduce clinical endpoints in patients with chronic systolic heart failure both in ICD and CRT-D subgroups. The absolute benefit seems to be higher in higher-risk populations with worse prognosis.

BackgroundMortality and morbidity are higher among patients with atrial fibrillation and heart failure than among those with heart failure alone. Catheter ablation for atrial fibrillation has been proposed as a means of improving outcomes among patients with heart failure who are otherwise receiving appropriate treatment.MethodsWe randomly assigned patients with symptomatic paroxysmal or persistent atrial fibrillation who did not have a response to antiarrhythmic drugs, had unacceptable side effects, or were unwilling to take these drugs to undergo either catheter ablation (179 patients) or medical therapy (rate or rhythm control) (184 patients) for atrial fibrillation in addition to guidelines-based therapy for heart failure. All the patients had New York Heart Association class II, III, or IV heart failure, a left ventricular ejection fraction of 35% or less, and an implanted defibrillator. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure.ResultsAfter a median follow-up of 37.8 months, the primary composite end point occurred in significantly fewer patients in the ablation group than in the medical-therapy group (51 patients [28.5%] vs. 82 patients [44.6%]; hazard ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.87; P=0.007). Significantly fewer patients in the ablation group died from any cause (24 [13.4%] vs. 46 [25.0%]; hazard ratio, 0.53; 95% CI, 0.32 to 0.86; P=0.01), were hospitalized for worsening heart failure (37 [20.7%] vs. 66 [35.9%]; hazard ratio, 0.56; 95% CI, 0.37 to 0.83; P=0.004), or died from cardiovascular causes (20 [11.2%] vs. 41 [22.3%]; hazard ratio, 0.49; 95% CI, 0.29 to 0.84; P=0.009).ConclusionsCatheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy. (Funded by Biotronik; CASTLE-AF ClinicalTrials.gov number, NCT00643188.)

Purpose Radiofrequency catheter ablation of typical atrial flutter can vary largely in duration from patient to patient. The purpose of this work was to determine optimal combination of ablation settings leading to the highest procedural efficacy. Methods Our retrospective multivariate analysis comprised 448 patients undergoing atrial flutter ablation with nonirrigated 8-mm catheters at 19 clinical centers. Four procedural variables were included in the prognostic model: preset maximum temperature, preset maximum power, catheter-tip material (gold vs. platinum-iridium), and ablation technique (maximum voltage-guided vs. conventional anatomical approach). Univariate and multivariate analyses were performed using the logistic regression (for acute ablation success) and Cox constant proportional hazard models (for cumulative ablation time). Results Significant multivariate predictors of acute ablation success were a higher preset maximum temperature (odds 1.083 per 1 °C, P  < 0.05) and gold-tip catheter (odds 2.096, P  < 0.05). Predictors of cumulative ablation time were the maximum voltage-guided ablation technique (hazard ratio 1.856, P  < 0.001), higher preset maximum temperature (hazard ratio 1.039 per 1 °C, P  < 0.001), and gold-tip catheter (hazard ratio 1.225, P  < 0.05). The combination of optimal settings (70 °C, 70 W, gold-tip catheter, maximum voltage-guided technique) increased the acute success rate from 91.7 % (for the entire study cohort) to 100 %, and reduced median cumulative ablation time from 8.3 to 4.3 min, median total procedure duration from 76 to 55 min, and median fluoroscopy time from 14 to 7 min. Conclusions The combination of maximum voltage-guided gold-tip ablation at 70 °C and 70 W was associated with 100 % ablation success and minimal ablation times for nonirrigated ablation of atrial flutter.

Aim The rapidly increasing prevalence and poor outcome of congestive heart failure have stimulated the development of different telemonitoring technologies. In this study, we monitored remotely self-measured body weight and blood pressure, in parallel with the data automatically transmitted by implantable cardioverter-defibrillators. The primary aim of this study was to evaluate the correlation between different parameters screened by these two telemonitoring systems. Methods and results Thirty-two patients in NYHA class III heart failure were followed for 164 ± 48 days after cardioverter-defibrillator implantation. In 29 patients, mean heart rate (MHR), resting heart rate (RHR), and patient activity (determined by implanted devices), weight and blood pressure measurements were received on 85% of all days when remote data transmissions were expected. Based on approximately 4,000 daily pairs of measurements pooled for all patients, weight inversely correlated with activity and with the difference between MHR and RHR. By contrast, blood pressure did not correlate with weight, activity, or the difference between MHR and RHR, but it correlated with MHR and RHR individually. Conclusion Body weight, patient activity, and the difference between MHR and RHR are mutually correlated and may reasonably contribute to an algorithm for predicting heart failure deterioration. Blood pressure appears to offer no additional value. As both genesis and symptoms of heart failure exacerbation are non-uniform and complex, the telemonitoring concepts for heart failure patients should employ continuous monitoring of multiple diagnostic parameters, rather than rely on a single parameter. Provided that patient compliance is strictly supervised, reliable data flow from sensors requiring patient involvement is possible.

Non-steroidal anti-inflammatory drugs (NSAID) are used to alleviate pain sensations during orthodontic therapy but are also assumed to interfere with associated pseudo-inflammatory reactions. In particular, the effects of partially selective COX-2 inhibition over the constitutively expressed COX-1 (11:1) on periodontal cells and tissue, as induced by the NSAID meloxicam, remain unclear. We investigate possible adverse side-effects and potentially useful beneficial effects during orthodontic therapy and examine underlying cellular and tissue reactions. We randomly assigned 63 male Fischer344 rats to three consecutive experiments of 21 animals each (cone-beam computed tomography; histology/serology; reverse-transcription quantitative real-time polymerase chain reaction) in three experimental groups ( n  = 7; control; orthodontic tooth movement [OTM] of the first/second upper left molars [NiTi coil spring, 0.25 N]; OTM with a daily oral meloxicam dose of 3 mg/kg). In vitro, we stimulated human periodontal ligament fibroblasts (hPDL) with orthodontic pressure (2 g/cm 2 ) with/without meloxicam (10 μM). In vivo, meloxicam significantly reduced serum C-reactive protein concentration, tooth movement velocity, orthodontically induced dentine root resorption (OIRR), osteoclast activity and the relative expression of inflammatory/osteoclast marker genes within the dental-periodontal tissue, while presenting good gastric tolerance. In vitro, we observed a corresponding significant decrease of prostaglandin E 2 /interleukin-6/RANKL(−OPG) expression and of hPDL-mediated osteoclastogenesis. By inhibiting prostaglandin synthesis, meloxicam seems to downregulate hPDL-mediated inflammation, RANKL-induced osteoclastogenesis and, consequently, tooth movement velocity by about 50%, thus limiting its suitability for analgesia during orthodontic therapy. However, its protective effects regarding OIRR and good tolerance profile suggest future prophylactic application, which merits its further investigation.

Orthodontic force application is well known to induce sterile inflammation, which is initially caused by the compression of blood vessels in tooth-supporting apparatus. The reaction of periodontal ligament cells to mechanical loading has been thoroughly investigated, whereas knowledge on tissue reactions of the dental pulp is rather limited. The aim of the present trial is to analyze the effect of orthodontic treatment on the induction and cellular regulation of intra-pulpal hypoxia. To investigate the effect of orthodontic force on dental pulp cells, which results in circulatory disturbances within the dental pulp, we used a rat model for the immunohistochemical analysis of the accumulation of hypoxia-inducible factor-1α in the initial phase of orthodontic tooth movement. To further examine the regulatory role of circulatory disturbances and hypoxic conditions, we analyze isolated dental pulp cells from human teeth with regard to their specific reaction under hypoxic conditions by means of flow cytometry, immunoblot, ELISA and real-time PCR on markers (Hif-1α, VEGF, Cox-2, IL-6, IL-8, ROS, p65). In vivo experiments showed the induction of hypoxia in dental pulp after orthodontic tooth movement. The induction of oxidative stress in human dental pulp cells showed up-regulation of the pro-inflammatory and angiogenic genes Cox-2, VEGF, IL-6 and IL-8. The present data suggest that orthodontic tooth movement affects dental pulp circulation by hypoxia, which leads to an inflammatory response inside treated teeth. Therefore, pulp tissue may be expected to undergo a remodeling process after tooth movement.

Bispecific T cell engager (BiTE) antibody constructs are successfully used as cancer therapeutics. We hypothesized that this treatment strategy could also be applicable for therapy of human cytomegalovirus (HCMV) infection, since HCMV-encoded proteins are abundantly expressed on the surface of infected cells. Here we show that a BiTE antibody construct directed against HCMV glycoprotein B (gB) and CD3 efficiently triggers T cells to secrete IFN-γ and TNF upon co-culture with fibroblasts infected with HCMV strain AD169, Towne or Toledo. Titration of gB expression levels in non-infected cells confirmed that already low levels of gB are sufficient for efficient triggering of T cells in presence of the BiTE antibody construct. Comparison of redirecting T cells with the bispecific antibody versus a chimeric antigen receptor (CAR) based on the same scFv showed a similar sensitivity for gB expression. Although lysis of infected target cells was absent, the BiTE antibody construct inhibited HCMV replication by triggering cytokine production. Notably, even strongly diluted supernatants of the activated T cells efficiently blocked the replication of HCMV in infected primary fibroblasts. In summary, our data prove the functionality of the first BiTE antibody construct targeting an HCMV-encoded glycoprotein for inhibiting HCMV replication in infected cells.