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Background and Objectives: Intravenous alteplase improves functional outcome after acute ischemic stroke. However, little is known about the effects on self-reported health-related quality of life (HRQoL)., Methods: WAKE-UP was a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in stroke with unknown onset time. HRQoL was assessed using the EuroQol five-dimensional questionnaire (EQ-5D) at 90 days, comprising the EQ-5D index and the EQ visual analogue scale (VAS). Functional outcome was assessed by the modified Rankin Scale (mRS). We calculated the effect of treatment on EQ-5D index and EQ VAS using multiple linear regression models. Mediation analysis was performed on stroke survivors to explore the extent to which the effect of alteplase on HRQoL was mediated by functional outcome., Results: Among 490 stroke survivors, the EQ-5D index was available for 452 (92.2%), of whom 226 (50%) were assigned to treatment with alteplase and 226 (50%) to placebo. At 90 days, mean EQ-5D index was higher, reflecting a better health state, in patients randomized to treatment with alteplase than with placebo (0.75 vs 0.67) with an adjusted mean difference of 0.07 (95% CI 0.02-0.12, p = 0.005). In addition, mean EQ VAS was higher with alteplase than with placebo (72.6 vs 64.9), with an adjusted mean difference of 7.6 (95% CI 3.9-11.8, p < 0.001). Eighty-five percent of the total treatment effect of alteplase on the EQ-5D index was mediated using the mRS score while there was no significant direct effect. By contrast, the treatment effect on the EQ VAS was mainly through the direct pathway (60%), whereas 40% was mediated by the mRS., Discussion: Assessment of patient-reported outcome measures reveals a potential benefit of intravenous alteplase for HRQoL beyond improvement of functional outcome., Trial Registration Information: ClinicalTrials.gov number, NCT01525290; EudraCT number, 2011-005906-32., (© 2022 American Academy of Neurology.)

Background: This study was conducted to determine the effect of hypothermic temperature control after in-hospital cardiac arrest (IHCA) on mortality and functional outcome as compared with normothermia., Methods: An investigator initiated, open-label, blinded-outcome-assessor, multicenter, randomized controlled trial comparing hypothermic temperature control (32-34°C) for 24 h with normothermia after IHCA in 11 hospitals in Germany. The primary endpoint was all-cause mortality after 180 days. Secondary end points included in-hospital mortality and favorable functional outcome using the Cerebral Performance Category scale after 180 days. A Cerebral Performance Category score of 1 or 2 was defined as a favorable functional outcome., Results: A total of 1055 patients were screened for eligibility and 249 patients were randomized: 126 were assigned to hypothermic temperature control and 123 to normothermia. The mean age of the cohort was 72.6±10.4 years, 64% (152 of 236) were male, 73% (166 of 227) of cardiac arrests were witnessed, 25% (57 of 231) had an initial shockable rhythm, and time to return of spontaneous circulation was 16.4±10.5 minutes. Target temperature was reached within 4.2±2.8 hours after randomization in the hypothermic group and temperature was controlled for 48 hours at 37.0°±0.9°C in the normothermia group. Mortality by day 180 was 72.5% (87 of 120) in hypothermic temperature control arm, compared with 71.2% (84 of 118) in the normothermia group (relative risk, 1.03 [95% CI, 0.79-1.40]; P =0.822). In-hospital mortality was 62.5% (75 of 120) in the hypothermic temperature control as compared with 57.6% (68 of 118) in the normothermia group (relative risk, 1.11 [95% CI, 0.86-1.46, P =0.443). Favorable functional outcome (Cerebral Performance Category 1 or 2) by day 180 was 22.5% (27 of 120) in the hypothermic temperature control, compared with 23.7% (28 of 118) in the normothermia group (relative risk, 1.04 [95% CI, 0.78-1.44]; P =0.822). The study was prematurely terminated because of futility., Conclusions: Hypothermic temperature control as compared with normothermia did not improve survival nor functional outcome at day 180 in patients presenting with coma after IHCA. The HACA in-hospital trial (Hypothermia After Cardiac Arrest in-hospital) was underpowered and may have failed to detect clinically important differences between hypothermic temperature control and normothermia., Registration: URL: https://www., Clinicaltrials: gov; Unique Identifier: NCT00457431.

Background: The randomized EAST-AFNET4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial-Atrial Fibrillation Network) demonstrated that early rhythm control (ERC) reduces adverse cardiovascular outcomes in patients with recently diagnosed atrial fibrillation and stroke risk factors. The effectiveness and safety of ERC in patients with multiple cardiovascular comorbidities is not known., Methods: These prespecified subanalyses of EAST-AFNET4 compared the effectiveness and safety of ERC with usual care (UC) stratified into patients with higher (CHA 2 DS 2 -VASc score ≥4) and lower comorbidity burden. Sensitivity analyses ignored sex (CHA 2 DS 2 -VA score)., Results: EAST-AFNET4 randomized 1093 patients with CHA 2 DS 2 -VASc score ≥4 (74.8±6.8 years, 61% female) and 1696 with CHA 2 DS 2 -VASc score <4 (67.4±8.0 years, 37% female). ERC reduced the composite primary efficacy outcome of cardiovascular death, stroke, or hospitalization for worsening of heart failure or for acute coronary syndrome in patients with CHA 2 DS 2 -VASc score ≥4 (ERC, 127/549 patients with events; UC, 183/544 patients with events; hazard ratio [HR], 0.64 [0.51-0.81]; P < 0.001) but not in patients with CHA 2 DS 2 -VASc score <4 (ERC, 122/846 patients with events; UC, 133/850 patients with events; HR, 0.93 [0.73-1.19]; P =0.56, P interaction =0.037). The primary safety outcome (death, stroke, or serious adverse events of rhythm control therapy) was not different between study groups in patients with CHA 2 DS 2 -VASc score ≥4 (ERC, 112/549 patients with events; UC, 132/544 patients with events; HR, 0.84 [0.65, 1.08]; P =0.175), but occurred more often in patients with CHA 2 DS 2 -VASc scores <4 randomized to ERC (ERC, 119/846 patients with events; UC, 91/850 patients with events; HR, 1.39 [1.05-1.82]; P =0.019, P interaction =0.008). Life-threatening events or death were not different between groups (CHA 2 DS 2 -VASc score ≥4, ERC, 84/549 patients with event, UC, 96/544 patients with event; CHA 2 DS 2 -VASc scores <4, ERC, 75/846 patients with event, UC, 73/850 patients with event). When female sex was ignored for the creation of higher and lower risk groups (CHA 2 DS 2 -VA score), the P interaction was not significant for the primary efficacy outcome ( P =0.25), but remained significant ( P =0.044) for the primary safety outcome., Conclusions: Patients with recently diagnosed atrial fibrillation and CHA 2 DS 2 -VASc score ≥4 should be considered for ERC to reduce cardiovascular outcomes, whereas those with fewer comorbidities may have less favorable outcomes with ERC., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01288352. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2010-021258-20. URL: https://www.isrctn.com/; Unique identifier: ISRCTN04708680.

Background: Even on optimal therapy, many patients with heart failure and atrial fibrillation experience cardiovascular complications. Additional treatments are needed to reduce these events, especially in patients with heart failure and preserved left ventricular ejection fraction., Methods: This prespecified subanalysis of the randomized EAST-AFNET4 trial (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) assessed the effect of systematic, early rhythm control therapy (ERC; using antiarrhythmic drugs or catheter ablation) compared with usual care (allowing rhythm control therapy to improve symptoms) on the 2 primary outcomes of the trial and on selected secondary outcomes in patients with heart failure, defined as heart failure symptoms New York Heart Association II to III or left ventricular ejection fraction [LVEF] <50%., Results: This analysis included 798 patients (300 [37.6%] female, median age 71.0 [64.0, 76.0] years, 785 with known LVEF). The majority of patients (n=442) had heart failure and preserved LVEF (LVEF≥50%; mean LVEF 61±6.3%), the others had heart failure with midrange ejection fraction (n=211; LVEF 40%-49%; mean LVEF 44 ± 2.9%) or heart failure with reduced ejection fraction (n=132; LVEF<40%; mean LVEF 31±5.5%). Over the 5.1-year median follow-up, the composite primary outcome of cardiovascular death, stroke, or hospitalization for worsening of heart failure or for acute coronary syndrome occurred less often in patients randomly assigned to ERC (94/396; 5.7 per 100 patient-years) compared with patients randomly assigned to usual care (130/402; 7.9 per 100 patient-years; hazard ratio, 0.74 [0.56-0.97]; P =0.03), not altered by heart failure status (interaction P value=0.63). The primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) occurred in 71 of 396 (17.9%) patients with heart failure randomly assigned to ERC and in 87 of 402 (21.6%) patients with heart failure randomly assigned to usual care (hazard ratio, 0.85 [0.62-1.17]; P =0.33). LVEF improved in both groups (LVEF change at 2 years: ERC 5.3±11.6%, usual care 4.9±11.6%, P =0.43). ERC also improved the composite outcome of death or hospitalization for worsening of heart failure., Conclusions: Rhythm control therapy conveys clinical benefit when initiated within 1 year of diagnosing atrial fibrillation in patients with signs or symptoms of heart failure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01288352. URL: http://www.controlled-trials.com; Unique identifier: ISRCTN04708680. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2010-021258-20.

Background: Recent data demonstrate promising effects on left ventricular dysfunction and left ventricular ejection fraction (LVEF) improvement following ablation for atrial fibrillation (AF) in patients with heart failure. We sought to study the relationship between LVEF, New York Heart Association class on presentation, and the end points of mortality and heart failure admissions in the CASTLE-AF study (Catheter Ablation for Atrial Fibrillation With Heart Failure) population. Furthermore, predictors for LVEF improvement were examined., Methods: The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function and New York Heart Association class were assessed at baseline (after randomization) and at each follow-up visit., Results: In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to >35% at the end of the study (odds ratio, 2.17; P <0.001). Compared with the pharmacological therapy arm, both ablation patient groups with severe (<20%) or moderate/severe (≥20% and <35%) baseline LVEF had a significantly lower number of composite end points (hazard ratio [HR], 0.60; P =0.006), all-cause mortality (HR, 0.54; P =0.019), and cardiovascular hospitalizations (HR, 0.66; P =0.017). In the ablation group, New York Heart Association I/II patients at the time of treatment had the strongest improvement in clinical outcomes (primary end point: HR, 0.43; P <0.001; mortality: HR, 0.30; P =0.001)., Conclusions: Compared with pharmacological treatment, AF ablation was associated with a significant improvement in LVEF, independent from the severity of left ventricular dysfunction. AF ablation should be performed at early stages of the patient's heart failure symptoms.

Background: Catheter ablation for ventricular tachycardia (VT) reduces the recurrence of VT in patients with implantable cardioverter-defibrillators (ICDs). The appropriate timing of VT ablation and its effects on mortality and heart failure progression remain a matter of debate. In patients with life-threatening arrhythmias necessitating ICD implantation, we compared outcomes of preventive VT ablation (undertaken before ICD implantation to prevent ICD shocks for VT) and deferred ablation after 3 ICD shocks for VT., Methods: The BERLIN VT study (Preventive Ablation of Ventricular Tachycardia in Patients With Myocardial Infarction) was a prospective, open, parallel, randomized trial performed at 26 centers. Patients with stable ischemic cardiomyopathy, a left ventricular ejection fraction between 30% and 50%, and documented VT were randomly assigned 1:1 to a preventive or deferred ablation strategy. The primary outcome was a composite of all-cause death and unplanned hospitalization for either symptomatic ventricular arrhythmia or worsening heart failure. Secondary outcomes included sustained ventricular tachyarrhythmia and appropriate ICD therapy. We hypothesized that preventive ablation strategy would be superior to deferred ablation strategy in the intention-to-treat population., Results: During a mean follow-up of 396±284 days, the primary end point occurred in 25 (32.9%) of 76 patients in the preventive ablation group and 23 (27.7%) of 83 patients in the deferred ablation group (hazard ratio, 1.09 [95% CI, 0.62-1.92]; P =0.77). On the basis of prespecified criteria for interim analyses, the study was terminated early for futility. In the preventive versus deferred ablation group, 6 versus 2 patients died (7.9% versus 2.4%; P =0.18), 8 versus 2 patients were admitted for worsening heart failure (10.4% versus 2.3%; P =0.062), and 15 versus 21 patients were hospitalized for symptomatic ventricular arrhythmia (19.5% versus 25.3%; P =0.27). Among secondary outcomes, the proportions of patients with sustained ventricular tachyarrhythmia (39.7% versus 48.2%; P =0.050) and appropriate ICD therapy (34.2% versus 47.0%; P =0.020) were numerically reduced in the preventive ablation group., Conclusions: Preventive VT ablation before ICD implantation did not reduce mortality or hospitalization for arrhythmia or worsening heart failure during 1 year of follow-up compared with the deferred ablation strategy. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02501005.

Objective: Stepped, collaborative, and coordinated approaches have been proposed as the optimal treatment strategy for somatic symptom and related disorders, but evidence supporting this strategy is lacking. The aim of this study was to assess the effectiveness of a guideline-based health care network for patients who are at high risk of somatoform disorder (Sofu-Net)., Methods: In a controlled, prospective, observer-blinded cluster cohort study, patients who were at high risk of somatoform disorder were recruited at 18 primary care practices in the Sofu-Net and at 15 primary care practices that provided care as usual (CAU). The primary outcome at 6-month follow-up was the rate at which the patients received mental health treatment since the establishment of Sofu-Net. The secondary outcomes included the patients' clinical symptom severity., Results: A total of 119 patients in the Sofu-Net intervention group and 100 patients in the CAU control group who were at high risk of somatoform disorder were followed for 6 months. A significantly greater proportion of Sofu-Net patients than CAU patients received mental health treatment (47.9% versus 31.0%; odds ratio = 1.96; 95% confidence interval, 1.07-3.58). However, the Sofu-Net group did not show greater reductions in clinical symptom burden compared with the CAU group., Conclusions: The treatment of somatoform disorders within a guideline-based health care network resulted in increased rates of mental health treatment but failed to improve patient clinical outcomes. Future investigations are needed to investigate the combined value of health care networks with specialized psychotherapy interventions in patients at high risk of somatic symptom and related disorders., Trial Registration: ISRCTN55870770.

Background: Ablation of atrial fibrillation (AF) is an established treatment option for symptomatic patients. It is not known whether complete pulmonary vein isolation (PVI) is superior to incomplete PVI with regard to the patients' clinical outcome., Methods and Results: Patients with drug-refractory, symptomatic paroxysmal AF were randomly assigned to either incomplete (group A) or complete PVI (group B). In group A, a persistent gap was intentionally left within the circumferential ablation line, whereas in group B, complete PVI without any gaps was intended. At 3 months, all patients underwent invasive reevaluation to assess the rate of persistent PVI. Clinical follow-up was based on daily 30-s transtelephonic ECG transmissions. Primary study end point was the time to first recurrence of (symptomatic or asymptomatic) AF. A total of 233 patients were enrolled (116 in group A and 117 in group B). AF recurrence within 3 months was observed in a total of 161 patients (136 [84.5%] with symptomatic and 25 [15.5%] with asymptomatic AF); AF recurred in 62.2% of group B patients and 79.2% of group A patients (P<0.001), for a difference in favor of complete PVI of 17.1% (95% confidence interval, 5.3%-28.9%). Invasive restudy in 103 group A patients and 93 group B patients revealed conduction gaps in 92 (89.3%) and 65 (69.9%) patients, respectively., Conclusions: This study proves the superiority of complete PVI over incomplete PVI with respect to AF recurrence within 3 months. However, the rate of electric reconduction 3 months after PVI is high in patients with initially isolated PVs., Clinical Trial Registration: URL: http://clinicaltrials.gov; Unique identifier: NCT00293943., (© 2016 American Heart Association, Inc.)

Background: In the meantime, catheter ablation is widely used for the treatment of persistent atrial fibrillation (AF). There is a paucity of data about long-term outcomes. This study evaluates (1) 5-year single and multiple procedure success and (2) prognostic factors for arrhythmia recurrences after catheter ablation of persistent AF using the stepwise approach aiming at AF termination., Methods and Results: A total of 549 patients with persistent AF underwent de novo catheter ablation using the stepwise approach (2007-2009). A total of 493 patients were included (Holter ECGs ≥ every 6 months). Mean follow-up was 59 ± 16 months with 2.1 ± 1.1 procedures per patient. Single and multiple procedure success rates were 20.1% and 55.9%, respectively (80% off antiarrhythmic drug). Antiarrhythmic drug-free multiple procedure success was 46%. Long-term recurrences (n=171) were paroxysmal AF in 48 patients (28%) and persistent AF/atrial tachycardia in 123 patients (72%). Multivariable recurrent event analysis revealed the following factors favoring arrhythmia recurrence: failure to terminate AF during index procedure (hazard ratio [HR], 1.279; 95% confidence interval [CI], 1.093-1.497; P = 0.002), number of procedures (HR, 1.154; 95% CI, 1.051-1.267; P = 0.003), female sex (HR, 1.263; 95% CI, 1.027-1.553; P = 0.027), and the presence of structural heart disease (HR, 1.236; 95% CI, 1.003-1.524; P = 0.047). AF termination was correlated with a higher rate of consecutive procedures because of atrial tachycardia recurrences (P = 0.003; HR, 1.71; 95% CI, 1.20-2.43)., Conclusions: Catheter ablation of persistent AF using the stepwise approach provides limited long-term freedom of arrhythmias often requiring multiple procedures. AF termination, the number of procedures, sex, and the presence of structural heart disease correlate with outcome success. AF termination is associated with consecutive atrial tachycardia procedures., (© 2015 American Heart Association, Inc.)

Objective: In Spring 2011, an unprecedented outbreak of Shiga toxin-producing Escherichia coli serotype O104:H4-associated hemolytic uremic syndrome occurred in Northern Germany. The aim of this study was to describe the clinical characteristics, treatments, and outcomes of critically ill patients with Shiga toxin-producing E. coli-associated hemolytic uremic syndrome during this outbreak., Design, Setting, and Patients: Multicenter, retrospective, observational study of critically ill adult patients with Shiga toxin-producing E. coli-associated hemolytic uremic syndrome in six hospitals in Hamburg, Germany, between May 2011 and August 2011., Measurements and Main Results: During the study period, 106 patients with Shiga toxin-producing E. coli-associated hemolytic uremic syndrome were admitted to eight ICUs. The median age was 40 years (range, 18-83) with a female:male ratio of 3:1. The median time from onset of clinical symptoms to hospital admission was 3 days and from hospital to ICU admission an additional 3 days. A total of 101 patients (95.3%) had acute renal failure and 78 (73.6%) required renal replacement therapy. Intubation and mechanical ventilation were required in 38 patients (35.8%) and noninvasive ventilation was required in 17 patients (16.0%). The median duration of invasive ventilation was 7 days (range, 1-32 days) and the median ICU stay was 10 days (range, 1-45 days). Fifty-one patients (48.1%) developed sepsis; of these 51 patients, 27 (25.4%) developed septic shock. Seventy patients (66.0%) developed severe neurological symptoms. Ninety-seven patients (91.5%) were treated with plasma exchange and 50 patients (47.2%) received eculizumab (monoclonal anti-C5 antibody). The mortality rate was 4.7%. Mild residual neurological symptoms were present in 21.7% of patients at ICU discharge, and no patient required renal replacement therapy 6 months after ICU admission., Conclusions: During the 2011 Shiga toxin-producing E. coli-associated hemolytic uremic syndrome outbreak in Germany, critical illness developed rapidly after hospital admission, often in young women. The infection was associated with severe neurological and renal symptoms, requiring mechanical ventilation and renal replacement therapy in a substantial proportion of patients. Overall, recovery was much better than expected.

Background and Purpose: Hemodynamic properties of brain arteriovenous malformations (AVMs) with risk factors for a future hemorrhage are essentially unknown. We hypothesized that AVMs with anatomic properties, which are associated with an increased rupture risk, exhibit different hemodynamic characteristics than those without these properties., Methods: Seventy-two consecutive patients with AVMs diagnosed by conventional angiography underwent MRI examination, including time-resolved 3-dimensional MR angiography. Signal-intensity curves derived from the time-resolved 3-dimensional MR angiography datasets were used to calculate relative blood flow transit times through the AVM nidus based on the time-to-peak parameter. For identification of characteristics associated with altered transit times, a multiple normal regression model was fitted with stepwise selection of the following regressors: intracranial hemorrhage, deep nidus location, infratentorial location, deep drainage, associated aneurysm, nidus size, draining venous stenosis, and number of draining veins., Results: A previous intracranial hemorrhage is the only characteristic that was associated with a significant alteration of the relative transit time, leading to an increase of 2.4 seconds (95% CI, 1.2-3.6 seconds;, P<0.001) without adjustment and 2.1 seconds (95% CI, 0.6-3.6 seconds; P=0.007) with adjustment for all other regressors considered. The association was independent of the bleeding age., Conclusions: Hemodynamic parameters do not seem useful for risk assessment of an AVM-related hemorrhage because only a previous AVM rupture leads to a significant and permanent alteration of the hemodynamic situation.

Background: Termination of persistent atrial fibrillation (AF) can be achieved through ablation, with the majority of patients terminating to an atrial tachycardia (AT) and fewer directly to sinus rhythm (SR). We aimed to identify potential predictors for the existence of a substrate for AT on termination to SR., Methods and Results: We assessed 95 persistent AF patients (age, 60+/-10 years) who underwent catheter ablation to the end point of AF termination. Forty patients terminated directly to SR (SRterm) and 55 to ATs (ATterm). Compared with the ATterm group, the SRterm group were younger (56+/-10 versus 63+/-9 years, P=0.001), had shorter durations of AF before ablation (9+/-26 versus 14+/-20 months, P<0.001), smaller left atrial diameters (41+/-5 versus 45+/-5 mm, P=0.015), and longer baseline AF cycle lengths (178+/-23 versus 159+/-31 ms, P=0.005). However, AF cycle length was the sole independent predictor of direct termination to SR. The most frequent AF termination site in SRterm patients was the pulmonary veins (53%), whereas in ATterm patients this was within the left atrium (58%). After follow-up of 12+/-6 months, there was a trend toward a greater proportion of patients in SR among those who terminated directly to SR after a single procedure. The most frequent type of recurrence was paroxysmal AF in SRterm patients and AT in ATterm patients., Conclusions: Patients who terminate to SR through ablation without an intermediate AT are characterized by a less altered arrhythmogenic substrate. Baseline AF cycle lengths emerged as a sole independent predictor of a substrate for consecutive arrhythmias.

Background: Termination of chronic atrial fibrillation (CAF) can be achieved by catheter ablation using a stepwise approach. However, there are limited data on the contribution of the right atrium to the CAF process. Furthermore, the prognostic value of CAF termination remains unclear., Methods and Results: Eighty-eight patients (61+/-10 years of age) underwent de novo ablation of CAF in 2006 at our institution. The ablation procedure was performed sequentially in the following order: pulmonary vein isolation, defragmentation of the left atrium, coronary sinus, and right atrium. Attempted procedural end point was termination of CAF. Consecutive arrhythmias occurring after AF termination were mapped, and ablation was attempted. AF termination was achieved in 68 (77%) patients: in 37 (55%) patients it occurred in the left atrium, in 18 (26%) patients in the right atrium, and in 13 (19%) patients in the coronary sinus. In 54 patients, at least one redo was performed (total number of procedures: 154). After the first redo, another 30 patients were in sinus rhythm (total 63), 8 patients were in atrial tachycardia (AT), and 17 patients were in AF. Another 11 patients underwent a second redo. After a mean follow-up of 20+/-4 months, 71 (81%) patients were in sinus rhythm, 1 (1%) patient was in AT, and 16 (18%) patients were in AF. Patients with CAF termination had predominantly ATs as recurrent arrhythmias (83%), whereas those without mainly presented with recurrent CAF (85%). The overall success rate in patients with CAF termination was 95% compared with 5% of patients without CAF termination in 2 procedures (n=12). In almost all redo procedures attributable to AT, at least 1 AT during redo was documented previously., Conclusions: AF termination is a prognostic important end point of catheter ablation for CAF. Termination of AF was achieved in both atria and the coronary sinus, suggesting a biatrial substrate of CAF. Subsequent arrhythmias often recur during follow-up and, therefore, should be targeted for ablation.

Background: Use of the transpulmonary thermodilution technique has been suggested for extended hemodynamic monitoring in critically ill patients. However, many of these patients also require renal replacement therapy (RRT). Therefore, we analyzed the influence of venovenous RRT on measurement of cardiac index (CI), intrathoracic blood volume index (ITBVI), and extravascular lung water index (EVLWI)., Methods: We studied 24 consecutive critically ill patients (15 males, 9 females; age 39-81, mean 62 yr) who had received a clinically indicated 5F femoral arterial catheter (PV2015L20, Pulsion Medical Systems, Germany), which was connected to a monitor (PiCCOplus, Pulsion Medical Systems, Germany). A 12F dialysis catheter (Trilyse Expert, Vygon) was either advanced from the vena femoralis into the vena cava inferior (n = 12) or placed into the superior vena cava (n = 12). Patients continuously received heparin for anticoagulation. Hemodynamic measurements were performed in triplicate by central venous injection of saline (15 mL, <8 degrees C) during RRT, during a brief interruption in RRT (by disconnection, without retransfusion), and immediately after reconnection. Ventilator settings, fluid status, and vasoactive drugs remained unchanged., Results: RRT was associated with significant changes in CI (mean change, -0.1 L/min/m(2), P = 0.003) and ITBVI (mean change, -18 mL/m(2), P = 0.02), whereas EVLWI was unaffected (mean change, +0.1 mL/kg, P = 0.42). The influence of RRT on CI, ITBVI, and EVLWI was not statistically different in both subgroups., Conclusions: RRT had no clinically relevant effect on measurement of CI, ITBVI, and EVLWI in patients with sepsis and maintained cardiac output. Furthermore, the dialysis catheter tip position had no significantly different influence under these conditions.

Background: The purpose of the present study was to examine whether the effect of coronary stenoses of variable severity on myocardial perfusion can be quantitatively assessed in vivo by analysis of fluorescent cardiac imaging (FCI) compared with the gold standard, the fluorescent microsphere method. FCI is a novel technology to visualize coronary vessels and myocardial perfusion intraoperatively using the indocyanine green dye with an infrared-sensitive imaging device., Methods and Results: Graded stenoses and total vessel occlusion of the left anterior descending coronary artery were created in 11 open-chest pigs. Stenoses were graded to reduce resting left anterior descending coronary artery flow by 25%, 50%, 75%, and 100% of baseline flow measured by transit-time flowmeter. FCI images were analyzed with a digital image processing system. The impairment of myocardial perfusion was quantified by background-subtracted peak fluorescence intensity and slope of fluorescence intensity obtained with FCI and compared with myocardial blood flow assessed by fluorescent microsphere. All stenoses resulted in an impairment of myocardial perfusion visualized by FCI. Occlusion of the left anterior descending coronary artery resulted in a total perfusion defect (no fluorescence intensity) of the corresponding anterior myocardial wall. During graded stenosis and total vessel occlusion, normalized background-subtracted peak fluorescence intensity and slope of fluorescence intensity decreased significantly (P<0.0001). Both background-subtracted peak fluorescence intensity (r=0.92, P<0.0001) and slope of fluorescence intensity (r=0.93, P<0.0001) analyzed by FCI demonstrated good linear correlation with fluorescent microsphere-derived myocardial blood flow., Conclusions: The impairment of myocardial perfusion in response to increased coronary stenosis severity and total vessel occlusion can be quantitatively assessed by FCI and correlates well with results obtained by fluorescent microsphere.

Background: Pancreatic infections and sepsis are major complications in severe acute pancreatitis (AP) with significant impact on management and outcome. We investigated the value of Procalcitonin (PCT) for identifying patients at risk to develop pancreatic infections in severe AP., Methods: A total of 104 patients with predicted severe AP were enrolled in five European academic surgical centers within 96 hours of symptom onset. PCT was measured prospectively by a semi-automated immunoassay in each center, C-reactive protein (CRP) was routinely assessed. Both parameters were monitored over a maximum of 21 consecutive days and in weekly intervals thereafter., Results: In contrast to CRP, PCT concentrations were significantly elevated in patients with pancreatic infections and associated multiorgan dysfunction syndrome (MODS) who all required surgery (n = 10) and in nonsurvivors (n = 8) early after onset of symptoms. PCT levels revealed only a moderate increase in patients with pancreatic infections in the absence of MODS (n = 7), all of whom were managed nonoperatively without mortality. A PCT value of > or =3.5 ng/mL on 2 consecutive days was superior to CRP > or =430 mg/L for the assessment of infected necrosis with MODS or nonsurvival as determined by ROC analysis with a sensitivity and specificity of 93% and 88% for PCT and 40% and 100% for CRP, respectively (P < 0.01). The single or combined prediction of the two major complications was already possible on the third and fourth day after onset of symptoms with a sensitivity and specificity of 79% and 93% for PCT > or =3.8 ng/mL compared with 36% and 97% for CRP > or =430 mg/L, respectively (P = 0.002)., Conclusion: Monitoring of PCT allows early and reliable assessment of clinically relevant pancreatic infections and overall prognosis in AP. This single test parameter significantly contributes to an improved stratification of patients at risk to develop major complications.

Acupuncture is widely used by patients with neck pain, but there is a lack of information about its effectiveness in routine medical care. The aim was to investigate the effectiveness of acupuncture in addition to routine care in patients with chronic neck pain compared to treatment with routine care alone. We performed a randomized controlled multicentre trial plus non-randomized cohort in general practices in Germany. 14,161 patients with chronic neck pain (duration >6 months). Patients were randomly allocated to an acupuncture group or a control group receiving no acupuncture. Patients in the acupuncture group received up to 15 acupuncture sessions over three months. Patients who did not consent to randomization received acupuncture treatment. All subjects were allowed to receive usual medical care in addition to study treatment. Neck pain and disability (NPAD Scale by Wheeler) after three months. Of 14,161 patients (mean age 50.9+/-13.1 years, 68% female) 1880 were randomized to acupuncture and 1886 to control, and 10,395 included into the non-randomized acupuncture group. At three months, neck pain and disability improved by 16.2 (SE: 0.4) to 38.3 (SE: 0.4); and by 3.9 (SE: 0.4) to 50.5 (SE: 0.4), difference 12.3 (p<0.001) in the acupuncture and control group, respectively. Treatment success was essentially maintained through six months. Non-randomized patients had more severe symptoms at baseline and showed higher neck pain and disability improvement compared to randomized patients. Treatment with acupuncture added to routine care in patients with chronic neck pain was associated with improvements in neck pain and disability compared to treatment with routine care alone.

Background: To date, donor-specific markers to predict outcome after heart transplantation (HTx) are unknown. Increased procalcitonin (PCT) levels have been found in infectious inflammation with systemic reactions and/or poor organ perfusion but have not been studied in heart donors. We evaluated PCT as a predictor of early graft failure-related mortality after HTx., Methods and Results: PCT and C-reactive protein (CRP) serum concentrations were measured in samples collected immediately before pericardium opening from 81 consecutive brain-dead multiple-organ donors. Donors for high-urgency-status recipients (n=2) were excluded from analysis. The remaining donors were retrospectively divided into 2 groups: donors for recipients who died within 30 days after HTx, after an early graft failure (group II, n=8), and all other donors (group I, n=71). No differences in donor and recipient demographic characteristics were found between groups. Areas under the receiver operating characteristic curves for graft failure-related mortality were 0.71 for PCT and 0.64 for CRP. A PCT value >2 ng/mL as a predictor of graft failure-related mortality had a specificity of 95.8% and sensitivity of 50.0%. The odds ratio for graft failure-related mortality for recipients of hearts from donors with PCT levels >2 ng/mL was 22.7 (unadjusted, 95% CI 3.7 to 137.8, P=0.0007) and 43.8 (after adjustment for prespecified potential confounders, 95% CI 1.4 to 1361.0, P=0.031)., Conclusions: A PCT level >2 ng/mL in a cardiac donor at the time of explantation appears to predict early graft failure-related mortality.

Prospectively acquired data from 941 patients staying greater than 24 h in a medical ICU were analyzed to determine the relevance of scoring on ICU admission by the following methods of outcome prediction: Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS), and Mortality Prediction Model (MPM). Analysis was performed separately for all patients (group A) and for a subsample (group B), obtained by excluding coronary care patients. Calculation of risk and classification of patients were carried out as recommended in the literature for MPM, APACHE II, and SAPS. In group A, sensitivities (correct prediction of hospital mortality) were 44.7%, 51.1%, and 21.2% and specificities (correct prediction of survival) were 84.5%, 85.4%, and 96.8%, respectively; overall correct classification rates were 73.3%, 75.8%, and 75.6%. In group B, sensitivities were slightly higher, but total correct classification rates did not reach group A levels. Goodness-of-fit testing showed low levels of fit for all methods in both groups. Application of APACHE II to diagnostic subgroups, using disease-adapted risk calculations, revealed marked inconsistencies between the estimated risk and the observed mortality. We conclude that the estimation of risk on admission by the three methods investigated might be helpful for global comparisons of ICU populations, although the lack of disease specificity reduces their applicability for severity grading of a given illness. The inaccuracy of these methods makes them ineffective for predicting individual outcome; thus, they provide little advantage in clinical decision-making.

Short-term i.v. infusion of streptokinase was performed in 93 patients within 6 hours after the onset of acute myocardial infarction. Twenty-six patients underwent angiography in the acute phase (group A) and 52 underwent angiography in the fourth week only (group B); 15 patients had no angiography. Seven patients died during the hospital stay and six suffered nonfatal reinfarctions. There were no bleeding complications. In 11 of 21 group A patients, occluded coronary arteries were opened within 1 hour after the streptokinase infusion was started. In 84% of groups A and B, the infarct-related coronary artery was patent in the fourth week. In 75% of the patent arteries, the residual luminal diameter stenosis was less than 70%. According to serial serum CK-MB curves, recanalization was achieved mostly within 1-2 hours. Myocardial salvage was indicated by improvement in local contraction disorders in the recanalized group A patients and by the significant relationship between infarct size and time from symptom onset to treatment in group B. These data suggest that a high-dose, short-term, i.v. infusion of streptokinase is a safe and efficient method of restoring coronary blood flow. Expeditious initiation of i.v. streptokinase infusion is a critical determinant for early recanalization and salvage of myocardium. Patients with thrombotically subtotal occlusion probably receive the most benefit. Evaluation of the true impact on survival and myocardial function will require controlled clinical trials.

The time of acute myocardial infarction was determined in all 1,741 patients of the ISAM (Intravenous Streptokinase in Acute Myocardial Infarction) Study, based on onset of clinical symptoms and evaluation of plasma CK-MB enzyme time-activity curves. The incidence of myocardial infarction was markedly increased between 6:00 AM and 12:00 noon compared with other times of day (p less than 0.001). Myocardial infarction occurred 3.8 times more frequently between 8:00 and 9:00 AM (hour of maximum incidence) than between 12:00 midnight and 1:00 AM (hour of minimum incidence). Time of myocardial infarction based on clinical and enzymatic methods correlated well (r = 0.95). Patients with higher or lower left ventricular ejection fraction, higher or lower degree of wall motion abnormalities and residual stenosis of the coronary arteries, and one-, two-, or three-vessel disease exhibited a similar circadian pattern, suggesting that the morning is a risk period for patients with mild as well as severe coronary artery disease. Only the group of patients receiving beta-adrenergic blocking therapy before the event did not show an increased morning incidence of myocardial infarction. This observation may contribute to an understanding of the mechanisms by which beta-blockers reduce the incidence of myocardial infarction. Further investigation of physiologic changes occurring during the morning period of increased risk of myocardial infarction may lead to better understanding of the disorder. Design and timing of cardioprotective medication may play a crucial role in improving prevention of acute myocardial infarction.