Effect of SGLT-2 inhibitors on arrhythmia events: insight from an updated secondary analysis of > 80,000 patients (the SGLT2i-Arrhythmias and Sudden Cardiac Death).

OBJECTIVE: We aimed to assess the effect of SGLT2i on arrhythmias by conducting a meta-analysis using data from randomized controlled trials(RCTs). BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown cardioprotective effects via multiple mechanisms that may also contribute to decrease arrhythmias risk. METHODS: We searched in databases (PubMed, Embase, Cochrane Library, and clinicaltrials.gov) up to April 2023. RCTs comparing SGLT2i with placebo were included. The effects of SGLT2i on atrial fibrillation(AF), atrial flutter(AFL), composite AF/AFL, ventricular fibrillation(VF), ventricular tachycardia(VT), ventricular extrasystoles(VES), sudden cardiac death(SCD) and composite VF/VT/SCD were evaluated. RESULTS: 33 placebo-controlled RCTs were included, comprising 88,098 patients (48,585 in SGLT2i vs. 39,513 in placebo). The mean age was 64.9 ± 9.4 years, 63.0% were male. The mean follow-up was 1.4 ± 1.1 years. The pooled-results showed that SGLT2i was associated with a significantly lower risk of AF [risk ratio(RR): 0.88, 95% confidence interval(CI) 0.78-1.00, P = 0.04] and composite AF/AFL (RR: 0.86, 95%CI 0.77-0.96, P = 0.01). This favorable effect appeared to be substantially pronounced in patients with HFrEF, male gender, dapagliflozin, and > 1 year follow-up. For SCD, only in heart failure patients, SGLT2i were found to be associated with a borderline lower risk of SCD (RR: 0.67, P = 0.05). No significant effects of SGLT2i on other ventricular arrhythmic outcomes were found. CONCLUSIONS: SGLT2i lowers the risks of AF and AF/AFL, and this favorable effect appeared to be particularly pronounced in patients with HFrEF, male gender, dapagliflozin, and longer follow-up (> 1 year). SGLT2i lowers the risk of SCD only in heart failure patients.

Evolving Role of Catheter Ablation for Atrial Fibrillation: Early and Effective Rhythm Control.

Catheter Ablation (CA) is an effective therapeutic option in treating atrial fibrillation (AF). Importantly, recent data show that CA as a rhythm control strategy not only significantly reduces AF burden, but also substantially improves clinical hard endpoints. Since AF is a progressive disease, the time of Diagnosis-to-Intervention appears crucial. Recent evidence shows that earlier rhythm control is associated with a lower risk of adverse cardiovascular outcomes in patients with early AF. Particularly, CA as an initial first line rhythm control strategy is associated with significant reduction of arrhythmia recurrence and rehospitalization in patients with paroxysmal AF. CA is shown to significantly lower the risk of progression from paroxysmal AF to persistent AF. When treating persistent AF, the overall clinical success after ablation remains unsatisfactory, however the ablation outcome in patients with "early" persistent AF appears better than those with "late" persistent AF. "Adjunctive" ablation on top of pulmonary vein isolation (PVI), e.g., ablation of atrial low voltage area, left atrial posterior wall, vein of Marshall, left atrial appendage, etc., may further reduce arrhythmia recurrence in selected patient group. New ablation concepts or new ablation technologies have been developing to optimize therapeutic effects or safety profile and may ultimately improve the clinical outcome.

Adjunctive Left Atrial Posterior Wall Isolation in Treating Atrial Fibrillation: Insight From a Large Secondary Analysis.

OBJECTIVES: This study evaluated the role of adjunctive left atrium posterior wall isolation (PWI) in preventing atrial fibrillation (AF) recurrence. BACKGROUND: The left atrium posterior wall is an arrhythmogenic substrate that contributes to the development of AF. METHODS: This was an updated pooled analysis that included clinical data regarding PWI plus pulmonary vein isolation (PVI) in treating AF. The primary outcome was recurrence of atrial tachyarrhythmias. RESULTS: A total of 26 studies with 3,287 patients with AF (age 61.7 ± 10.8 years) were included. Mean follow-up was 15.2 ± 8.4 months. Procedural success to achieve PWI was 92.8%. In paroxysmal AF, adjunctive PWI did not reduce the recurrence of all atrial arrhythmias (P = 0.21) or AF (P = 0.37); however, in persistent AF, adjunctive PWI was associated with substantially lower recurrence of all atrial arrhythmias (risk ratio: 0.74; P < 0.001) and AF (risk ratio: 0.67; P = 0.01), particularly when randomized data were included. Subgroup analyses based on meta-regression demonstrated that patients with older age, a larger left atrial diameter, and persistent AF benefited more significantly from the adjunctive PWI. Adjunctive PWI using either radiofrequency or a cryoballoon reduced AF recurrence, whereas using radiofrequency seemed to be associated with higher recurrence rate of atrial tachycardias and/or atrial flutter. Non-BOX adjunctive PWI rather than BOX PWI was associated with significantly lower recurrence of AF. The incidence of procedural adverse events between the PVI+PWI (3.2%) and PVI (2.8%) groups was low and similar. PVI+PWI needed longer ablation and/or procedural time but had similar fluoroscopy time. CONCLUSIONS: Adjunctive PWI can be achieved in most patients without compromising safety. Patients with persistent AF appear to benefit from this approach. The ablation technology and/or approach may affect the clinical outcome of PWI.

Anticoagulation in atrial fibrillation and liver disease: a pooled-analysis of >20 000 patients.

AIMS: Anticoagulation for atrial fibrillation patients with liver disease represents a clinical dilemma. We sought to evaluate the efficacy/safety of different anticoagulation, i.e. vitamin K antagonist (VKA) and non-VKA oral anticoagulants (NOACs) in such patient group. METHODS AND RESULTS: This was a pooled-analysis enrolling up-to-date clinical data. Two subsets: subset A (VKA vs. Non-Anticoagulation) and subset B (NOACs vs. VKA) were pre-specified. The study outcomes were ischaemic stroke (IS)/thromboembolism (TE), major bleeding (MB), intracranial bleeding (ICB), gastrointestinal bleeding (GIB), and all-cause mortality. A total of 20 042 patients' data were analysed (subset A: N = 10 275, subset B: N = 9767). Overall mean age: 71 ± 11 years, mean CHA2DS2-VASc score: 4.0 ± 1.8, mean HAS-BLED score: 3.6 ± 1.2. The majority of the patients had Child-Pugh category (A-B). As compared with Non-Anticoagulation, VKA seemed to reduce the risk of IS/TE [odds ratio (OR): 0.60, P = 0.05], but heighten the risk of all-bleeding events including MB (OR: 2.81, P = 0.01), ICB (OR: 1.60, P = 0.01), and GIB (OR: 3.32, P = 0.01). When compared with VKA, NOACs had similar efficacy in reducing the risk of IS/TE (OR: 0.82, P = 0.64), significantly lower risk of MB (OR: 0.54, P = 0.0003) and ICB (OR: 0.35, P < 0.0001), and trend towards reduced risk of GIB (OR: 0.72, P = 0.12) and all-cause mortality (OR: 0.79, P = 0.35). The favourable effects were maintained in subgroups of individual NOAC. CONCLUSIONS: VKA appears to reduce the risk of IS/TE but increase all-bleeding events. NOACs have similar effect in reducing the risk of IS/TE and have significantly lower risk of MB and ICB as compared with VKA. NOACs seem to be associated with better clinical outcome than VKA in patients with mild-moderate liver disease.

Catheter ablation vs. antiarrhythmic drugs as 'first-line' initial therapy for atrial fibrillation: a pooled analysis of randomized data.

AIMS: Catheter ablation (CA) is recommended for patients with atrial fibrillation (AF) after failure of antiarrhythmic drugs (AADs). The role of CA as 'initial therapy' for AF is to be determined. METHODS AND RESULTS: Following PRISMA guideline an up-to-date pooled analysis of randomized data comparing ablation vs. AADs as first-line therapy for symptomatic AF was performed. The primary outcome was recurrence of atrial tachyarrhythmia. The secondary outcomes were improvement in quality-of-life (QoL) and major adverse events. A total of 997 patients from five randomized trials were enrolled (mean age 57.4 years, 68.6% male patients, 98% paroxysmal AF, mean follow-up 1.4 years). The baseline characteristics were similar between the ablation and AADs group. Overall pooled analysis showed that, as compared with AADs, CA as first-line therapy was associated with significantly higher freedom from arrhythmia recurrence (69% vs. 48%, odds ratio: 0.36, 95% confidence interval: 0.27-0.48, P < 0.001). This significance was maintained in subgroup analyses of 1- and 2-year follow-up (P < 0.001). Catheter ablation was associated with significantly greater improvement in QoL regarding AFEQT score and 36-Item Short-Form Health Survey score. The incidence of serious adverse events between ablation and AADs group (5.6% vs. 4.9%, P = 0.62) was similar. CONCLUSIONS: Catheter ablation as 'initial therapy' was superior to AADs in maintenance of sinus rhythm and improving QoL for patients with symptomatic paroxysmal AF, without increasing risk of serious adverse events.

Comparison of Left Atrial Appendage Occlusion versus Non-Vitamin-K Antagonist Oral Anticoagulation in High-Risk Atrial Fibrillation: An Update.

Transcatheter left atrial appendage occlusion (LAAO) is non-inferior to vitamin K antagonists (VKAs) in preventing thromboembolic events in atrial fibrillation (AF). Non-vitamin K antagonists (NOACs) have an improved safety profile over VKAs; however, evidence regarding their effect on cardiovascular and neurological outcomes relative to LAAO is limited. Up-to-date randomized trials or propensity-score-matched data comparing LAAO vs. NOACs in high-risk patients with AF were pooled in our study. A total of 2849 AF patients (LAAO: 1368, NOACs: 1481, mean age: 75 ± 7.5 yrs, 63.5% male) were enrolled. The mean CHA2DS2-VASc score was 4.3 ± 1.7, and the mean HAS-BLED score was 3.4 ± 1.2. The baseline characteristics were comparable between the two groups. In the LAAO group, the success rate of device implantation was 98.8%. During a mean follow-up of 2 years, as compared with NOACs, LAAO was associated with a significant reduction of ISTH major bleeding (p = 0.0002). There were no significant differences in terms of ischemic stroke (p = 0.61), ischemic stroke/thromboembolism (p = 0.63), ISTH major and clinically relevant minor bleeding (p = 0.73), cardiovascular death (p = 0.63), and all-cause mortality (p = 0.71). There was a trend toward reduction of combined major cardiovascular and neurological endpoints in the LAAO group (OR: 0.84, 95% CI: 0.64-1.11, p = 0.12). In conclusion, for high-risk AF patients, LAAO is associated with a significant reduction of ISTH major bleeding without increased ischemic events, as compared to "contemporary NOACs". The present data show the superior role of LAAO over NOACs among high-risk AF patients in terms of reduction of major bleeding; however, more randomized controlled trials are warranted.

Rhythm control for patients with atrial fibrillation complicated with heart failure in the contemporary era of catheter ablation: a stratified pooled analysis of randomized data.

AIMS: The optimal treatment for patients with atrial fibrillation (AF) and heart failure (HF) has been a subject of debate for years. We aimed to evaluate the efficacy and safety of rhythm control strategy in patients with AF complicated with HF regarding hard clinical endpoints. METHODS AND RESULTS: Up-to-date randomized data comparing rhythm control using antiarrhythmic drugs (AADs) vs. rate control (Subset A) or rhythm control using catheter ablation vs. medical therapy (Subset B) in AF and HF patients were pooled. The primary outcomes were all-cause mortality, re-hospitalization, stroke, and thromboembolic events. A total of 11 studies involving 3598 patients were enrolled (Subset A: 2486; Subset B: 1112). As compared with medical rate control, the AADs rhythm control was associated with similar all-cause mortality [odds ratio (OR): 0.96, P = 0.65], significantly higher rate of re-hospitalization (OR: 1.25, P = 0.01), and similar rate of stroke and thromboembolic events (OR: 0.91, P = 0.76,); however, as compared with medical therapy, catheter ablation rhythm control was associated with significantly lower all-cause mortality (OR: 0.51, P = 0.0003), reduced re-hospitalization rate (OR: 0.44, P = 0.003), similar rate of stroke events (OR: 0.59, P = 0.27), greater improvement in left ventricular ejection fraction [weighted mean difference (WMD): 6.8%, P = 0.0004], lower arrhythmia recurrence (29.6% vs. 80.1%, OR: 0.04, P < 0.00001), and greater improvement in quality of life (Minnesota Living with Heart Failure Questionnaire score) (WMD: -9.1, P = 0.007). CONCLUSION: Catheter ablation as rhythm control strategy substantially improves survival rate, reduces re-hospitalization, increases the maintenance rate of sinus rhythm, contributes to preserve cardiac function, and improves quality of life for AF patients complicated with HF.

Association of Preoperative Renin-Angiotensin System Inhibitors With Prevention of Postoperative Atrial Fibrillation and Adverse Events: A Systematic Review and Meta-analysis.

Importance: Postoperative atrial fibrillation (POAF) is a well-known complication after cardiac surgery. Renin-angiotensin system inhibitors (RASIs) have been suggested as an upstream therapy for selected patients with AF; however, evidence in the surgical setting is limited. Objective: To evaluate the role of preoperative RASIs in prevention of POAF and adverse events for patients undergoing cardiac surgery. Data Sources: The PubMed database and the Cochrane Library from inception until December 31, 2018, were searched by using the keywords renin-angiotensin system inhibitors OR angiotensin-converting enzyme inhibitors OR angiotensin receptor blocker OR aldosterone antagonist AND cardiac surgery. ClinicalTrials.gov was searched from inception until December 31, 2018, by using the keywords postoperative atrial fibrillation. Study Selection: Randomized clinical trials (RCTs) and observational studies comparing the association between preoperative RASI treatment vs no preoperative RASI treatment (control group) and the incidence of POAF were identified. Eleven unique studies met the selection criteria. Data Extraction and Synthesis: Pooled analysis was performed using a random-effects model. Sensitivity and subgroup analyses of RCTs were performed to test the stability of the overall effect. Metaregression was conducted to explore potential risk of bias. Main Outcomes and Measures: The primary outcome was POAF, and the secondary outcomes included rates of stroke and mortality and duration of hospitalization. Results: Eleven unique studies involving 27 885 unique patients (74.4% male; median age, 65 years [range, 58.5-74.5 years]) were included. Compared with the control group, the RASI group did not have a significantly reduced risk of POAF (odds ratio [OR], 1.04; 95% CI, 0.91-1.19; P = .55; z = 0.60), stroke (OR, 0.86; 95% CI, 0.62-1.19; P = .37; z = 0.90; without significant heterogeneity, P = .11), death (OR, 1.07; 95% CI, 0.85-1.35; P = .56; z = 0.59; without significant heterogeneity, P = .12), composite adverse cardiac events (OR, 1.04; 95% CI, 0.91-1.18; P = .58; z = 0.56), or a reduced hospital stay (weighted mean difference, -0.04; 95% CI, -1.05 to 0.98; P = .94; z = 0.07) using a random-effects model. Pooled analysis focusing on RCTs showed consistent results. The primary overall effect was maintained in sensitivity and subgroup analyses. Metaregression showed that male sex was significantly associated with POAF (τ2 = 0.0065; z = 3.47; Q = 12.047; P < .001) and that use of ß-blockers was associated with a significantly reduced risk in developing POAF (τ2 = 0.018; z = -2.24; Q = 5.0091; P = .03). Conclusions and Relevance: The findings from this study suggest that preoperative RASI treatment does not offer additional benefit in reducing the risk of POAF, stroke, death, and hospitalization in the setting of cardiac surgery. The results provide no support for conventional use of RASIs for the possible prevention of POAF and adverse events in patients undergoing cardiac surgery; further randomized data, particularly among those patients with heart failure, are needed.

Ablation of Ischemic Ventricular Tachycardia Using a Multipolar Catheter and 3-dimensional Mapping System for High-density Electro-anatomical Reconstruction.

Ventricular tachycardia (VT) in patients with ischemic cardiomyopathy mainly results from endocardial scars after myocardial infarction; those scars represent zones of slow conduction that allow the occurrence and maintenance of reentrant circuits. Catheter ablation enables substrate modification of those low voltage areas and thus can help to alter the scar tissue in such a way that arrhythmias cannot appear anymore. Hospitalizations of concerned patients decrease, quality of life and outcome rise. Consequently, VT ablation represents a growing field in electrophysiology, especially for patients with endocardial scars in ischemic heart disease after myocardial infarction. However, ablation of ventricular tachycardia remains one of the most challenging procedures in the electrophysiology lab. Precise scar definition and localization of abnormal potentials are critical for ablation success. The following manuscript describes the use of a multipolar mapping catheter and 3-dimensional (3D) mapping system to create a high density electro-anatomical map of the left ventricle including a precise scar representation as well as mapping of fractionated and late potentials in order to allow a highly accurate substrate modification.

Synergy of pulmonary vein isolation and catheter renal denervation in atrial fibrillation complicated with uncontrolled hypertension: Mapping the renal sympathetic nerve and pulmonary vein (the pulmonary vein isolation plus renal denervation strategy)?

INTRODUCTION: Disturbance of sympathetic and vagal nervous system participates in the pathogenesis of hypertension and atrial fibrillation (AF). Renal denervation (RDN) can modulate autonomic nervous activity and reduce blood pressure (BP) in hypertensive patients. We aimed to evaluate the effect of RDN combined with pulmonary vein isolation (PVI) in patients with AF and hypertension. METHODS: Clinical trials including randomized data comparing PVI plus RDN vs PVI alone were enrolled. Primary outcome was incidence of AF recurrence after procedure. RESULTS: A total of 387 patients, of them 252 were randomized and were enrolled. Mean age was 57 ± 10 years, 71% were male, and mean left ventricular ejection fraction was 57.4% ± 6.9%. Follow-up for randomized data was 12 months. Overall comparison for primary outcome showed that PVI + RDN was associated with significantly lower AF recurrence as compared with PVI alone (35.8% vs 55.4%, P < 0.0001). This advantageous effect was consistently maintained among randomized patients (37.3% vs 61.9%, odds ratio = 0.37, P = 0.0001), and among patients with implanted devices for detection of AF recurrence (38.9% vs 61.6%, P = 0.007). Post-hoc sensitivity and regression analysis demonstrated very good stability of this primary result. Pooled Kaplan-Meier analysis further showed that PVI + RDN was associated with significantly higher freedom from AF recurrence as compared with PVI alone (log-rank test, P = 0.001). Besides, RDN resulted in significant BP reduction without additionally increasing the risk of adverse events. CONCLUSIONS: RDN may provide synergetic effects with PVI to reduce the burden of AF and improve BP control in patients with AF and uncontrolled hypertension.

Procedural Outcomes and Survival After Catheter Ablation of Ventricular Tachycardia in Relation to Electroanatomical Substrate in Patients With Nonischemic-Dilated Cardiomyopathy: The Role of Unipolar Voltage Mapping.

INTRODUCTION: In patients with ischemic cardiomyopathy the size of bipolar low-voltage areas (LVA) in electroanatomical maps (EAM) was associated with poorer outcomes after catheter ablation (CA) of ventricular tachycardia (VT). However, the effect of LVA size on the survival after VT ablation in patients with nonischemic dilated cardiomyopathy (NIDCM) has not been studied. METHODS AND RESULTS: In 55 patients with NIDCM (48 male, age 61 ± 16 years, ejection fraction 32 ± 13%) an EAM to delineate the bipolar and unipolar LVAs was performed in 52 (94.5%) patients endocardially, in 24 (43.6%) patients epicardially, and in 21 (38.2%) patients on both surfaces. Additionally, activation mapping of the VT was possible in 22 (40%) patients. CA with lines transecting the scar and targeting late potentials was performed in all patients. Complete VT noninducibility at the end was achieved in 40 (72.7%) patients. During the median follow-up of 22 (interquartile range IQR 6, 34) months, VT recurrences were observed in 30 (54.5%) and cardiac death in 14 (25.5%) patients. The ROC analysis revealed that the size of endocardial unipolar LVA (<8.3 mV) was associated with cardiac death (AUC 0.89, 95% CI 0.79-0.98, P <0.0001). UVA = 145 cm2 discriminates for cardiac death with 83% sensitivity and 78% specificity. Endocardial UVA > 145 cm2 was a predictor for cardiac death (adjusted HR = 6.9; P = 0.014) and UVA ≥ 54% (of total endocardial LV surface) for VT recurrence (adjusted HR = 3.5; P = 0.016). CONCLUSION: The size of endocardial unipolar LVA (<8.3 mV) was a strong and independent predictor for cardiac mortality and VT recurrence in patients with NIDCM.

Catheter ablation of ventricular tachycardia and mortality in patients with nonischemic dilated cardiomyopathy: can noninducibility after ablation be a predictor for reduced mortality?

BACKGROUND: Data on outcomes after catheter ablation of ventricular tachycardia (VT) in patients with nonischemic dilated cardiomyopathy (NIDCM) are insufficient. We aimed to investigate the effects of successful catheter ablation of VT on cardiac mortality in patients with NIDCM. METHODS AND RESULTS: One hundred two patients with NIDCM (86 men; mean age, 58.8±15.2 years; mean ejection fraction, 33.3±11.9%) underwent VT ablation. After catheter ablation, a programmed ventricular stimulation to test for success was performed. Complete VT noninducibility was achieved in 62 (61%) patients and partial success or failure in 32 (31%) patients. During 2 years of follow-up, VT recurrence was observed in 33 patients (53%) without inducible VTs and in 24 patients (75%) with inducible VT inducible (P=0.041). VT inducibility was associated with higher VT recurrence (adjusted hazard ratio, 1.84; 95% confidence interval, 1.08-3.13; P=0.025). The primary end point of all-cause mortality was reached in 9 patients (15%) with noninducible VTs versus 11 patients (34%) with inducible sustained VTs (P=0.026). VT inducibility was associated with all-cause mortality (adjusted hazard ratio, 2.73; 95% confidence interval, 1.003-7.43; P=0.049). CONCLUSIONS: In patients with NIDCM and recurrent sustained VTs, a complete ablation of all inducible VTs may be achieved in 60% of the cases. The complete noninducibility may be a preferable end point of ablation because it was associated with better long-term success. Importantly, if possible to achieve through ablation, a complete VT noninducibility was associated with reduction of the likelihood for all-cause mortality in patients with NIDCM.

Invasive versus non-invasive cooling after in- and out-of-hospital cardiac arrest: a randomized trial.

INTRODUCTION: Mild induced hypothermia (MIH) is indicated for comatose survivors of sudden cardiac arrest (SCA) to improve clinical outcome. In this study, we compared the efficacy of two different cooling devices for temperature management in SCA survivors. METHODS: Between April 2008 and August 2009, 80 patients after survived in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) were included in this prospective, randomized, single center study. Hypothermia was induced after randomization by either invasive Coolgard(®) cooling or non-invasive ArcticSun(®) surface cooling at 33.0 °C core body temperature for 24 h followed by active rewarming. The primary endpoint was defined as the efficacy of both cooling systems, measured by neuron-specific enolase (NSE) levels as a surrogate parameter for brain damage. Secondary efficacy endpoints were the clinical and neurological outcome, time to start of cooling and reaching the target temperature, target temperature-maintenance and hypothermia-associated complications. RESULTS: NSE at 72 h did not differ significantly between the 2 groups with 16.5 ng/ml, interquartile range 11.8-46.5 in surface-cooled patients versus 19.0 ng/ml, interquartile range 11.0-42.0 in invasive-cooled patients, p = 0.99. Neurological and clinical outcome was similar in both groups. Target temperature of 33.0 °C was maintained more stable in the invasive group (33.0 versus 32.7 °C, p < 0.001). Bleeding complications were more frequent with invasive cooling (n = 17 [43.6 %] versus n = 7 [17.9 %]; p = 0.03). CONCLUSION: Invasive cooling has advantages with respect to temperature management over surface cooling; however, did not result in different outcome as measured by NSE release in SCA survivors. Bleeding complications were more frequently encountered by invasive cooling.

[Beneficial outcomes of an interdisciplinary psychoeducative group intervention for patients with malignant gliomas and their relatives]. / Interdisziplinäre Psychoedukation für Hirntumorpatienten und deren Angehörige.

BACKGROUND: To assess the impact of psychoeducative group interventions on patients with high-grade glioma (glioblastoma, mixed glioma, and astrocytoma) and their relatives. METHODS: A total of one hundred and four patients and relatives underwent group interventions between September 2007 and May 2010 and were coached by a psychologist and a physician in the context of an interdisciplinary meeting. Questionnaires were distributed after every meeting. RESULTS: In general, group interventions were experienced as helpful to discuss psychic aspects, new life circumstances, and medical questions. CONCLUSIONS: Psychoeducative group interventions represent an important support for brain tumor patients and their relatives for discussing anxiety, concerns, and needs and thus improve their quality of life.

New conventional long-term survival normovolemic cardiac arrest pig model.

AIM OF THE STUDY: A reproducible long-term intensive care and outcome cardiac arrest model for exploring new cerebral preservation strategies is needed. We tried to determine effects and limitations of current therapies after different 'no-flow' times. METHODS: Thirty-five female Large White Breed pigs (26-37kg) were included in the study. Three pigs served as sham animals without cardiac arrest (CA). Ventricular fibrillation (VF) CA was induced in 32 animals for 0, 7, 10 and 13min (each group consisting of 8 animals), followed by 8min of chest compressions, mechanical ventilation and vasopressors. Thereafter, up to 3 defibrillations were delivered. After restoration of spontaneous circulation (ROSC), the animals underwent intensive care for 20h. Neurologic examination was performed at designated time points using a neurologic deficit (ND) and an overall performance category (OPC) score. RESULTS: Restoration of spontaneous circulation was achieved in 8 of 8 animals in the 0min-group, 6 of 8 in the 7min-group, 7 of 8 in the 10min-group and 0 of 8 in the 13min-group. All animals of the sham-group and 0min-group were neurologically intact survivors; the 7 and 10min-groups showed a median ND of 55%(26;94) and 73%(58;78), respectively. There were no significant differences between the 7 and 10min-groups regarding OPC and NDS. Coronary perfusion pressure during CPR decreased concordantly with 'no-flow' times with a tendency towards significance. CONCLUSION: This study established a reproducible cardiac arrest and resuscitation model in pigs which will be used to test novel resuscitation strategies to improve neurologic outcome after cardiac arrest.

The importance of surface area for the cooling efficacy of mild therapeutic hypothermia.

AIM OF THE STUDY: Mild hypothermia after cardiac arrest should be induced as soon as possible. There is a need for improved feasibility and efficacy of surface cooling in ambulances. We investigated which and how much area of the body surface should be covered to guarantee a sufficient cooling rate. METHODS: Each of five adult, human-sized pigs (88-105kg) was randomly cooled in three phases with pads that covered different areas of the body surface corresponding to humans (100% or 30% [thorax and abdomen] or 7% [neck]). The goal was to quickly lower brain temperature (Tbr) from 38 to 33°C within a maximum of 120min. Linear regression analysis was used to test the association between cooling efficacy and surface area. Data are presented as mean±standard deviation. RESULTS: The 100% and 30% cooling pads decreased the pigs' Tbr from 38 to 33°C within 33±7min (8.2±1.6°C/h) and 92±24min (3.6±1.1°C/h). The 7% achieved a final Tbr of 35.8±0.7°C after 120min (1.1±0.4°C/h). The 30% and 7% cooling surface areas achieved 37±11% and 15±7% of the cooling rate compared to the 100% cooling pads. For every additional percent of surface area cooled, the cooling rate increased linearly by 0.07°C/h (95% CI 0.05-0.09, p=0.001). No skin lesions were observed. CONCLUSIONS: The cooling pads were effective and safe for rapid induction of mild hypothermia in adult, human-sized pigs, depending on the percentage of body surface area covered. Covering only the neck, chest, and abdomen might achieve satisfactory cooling rates.

Distribution of neuropathological lesions in pig brains after different durations of cardiac arrest.

AIM OF THE STUDY: To evaluate all brain regions reported to be selectively vulnerable to global ischaemia in a pig cardiac arrest model with different durations of no-flow by establishing a semi-quantitative brain histopathologic scoring system and to compare histological damage with neurological deficits. METHODS: In a prospective randomised laboratory investigation, 35 female Large White pigs weighing 35-45 kg underwent ventricular fibrillation cardiac arrest for 0, 7, 10 or 13 min. In the brains of all animals that survived until the final endpoint (72 h post-arrest), 22 distinct regions were evaluated on paraffin-embedded sections in terms of type and extent of lesions. The results of the histological examination were compared to the results of a neurological outcome evaluation after 72 h. RESULTS: Significant differences were found in all cortex regions, the caudate nucleus and putamen, the hippocampal formation, the cerebellar cortex, and the thalamus between the ischaemic groups (7- and 10-min groups) and the control group (0-min group). No 13-min group animal survived. The main findings were neuronal necrosis and oedema. In animals from the 10-min group, many neurons were reabsorbed in the cerebral cortex, caudate nucleus and cerebellar granule cell layer. There was a highly significant correlation between histological damage and neurological deficits. CONCLUSIONS: The pattern of neuronal lesions in this pig model bear good resemblance to the pattern known in humans and other animal models. The amount of histological lesions in selectively vulnerable brain regions correlates to neurological outcome.

Cold aortic flush and chest compressions enable good neurologic outcome after 15 mins of ventricular fibrillation in cardiac arrest in pigs.

OBJECTIVE: The induction of deep cerebral hypothermia via ice-cold saline aortic flush during prolonged ventricular fibrillation cardiac arrest, followed by hypothermic stasis and delayed resuscitation (emergency preservation and resuscitation), improved neurologic outcome after cardiac arrest in pigs, as compared to conventional resuscitation. We hypothesized that emergency preservation and resuscitation with chest compressions would further improve outcome in the same model. DESIGN: Prospective experimental study. SETTING: University research laboratory. SUBJECTS: : Twenty-four female, large, white breed pigs (27-37 kg). INTERVENTIONS: Fifteen minutes of ventricular fibrillation cardiac arrest were followed by 20 mins of resuscitation with chest compressions (control, n = 8), deep cerebral hypothermia via 200 mL/kg 4 degrees C saline aortic flush and hypothermic stasis (emergency preservation and resuscitation, n = 8), and emergency preservation and resuscitation combined with chest compressions (emergency preservation and resuscitation plus chest compressions, n = 8). At 35 mins after cardiac arrest, cardiopulmonary bypass was initiated, followed by defibrillation. Mild hypothermia was continued for 20 hrs. Pigs were evaluated after 9 days using a neurologic deficit (neurologic deficit score: 100% = brain dead; 0%-10% = normal) and an overall performance category score (overall performance category score: 1 = normal; 2 = slightly handicapped; 3 = severely handicapped; 4 = comatose; 5 = dead/brain dead). MEASUREMENTS AND MAIN RESULTS: Brain temperature decreased from 38.5 degrees C to 15.3 degrees C +/- 3.3 degrees C in the emergency preservation and resuscitation group, and to 11.3 degrees C +/- 1.2 degrees C in the emergency preservation and resuscitation plus chest compressions group. In the control group, restoration of spontaneous circulation was achieved in four out of eight pigs, and one survived to 9 days. In the emergency preservation and resuscitation group, restoration of spontaneous circulation was achieved in seven out of eight pigs and five survived; in the emergency preservation and resuscitation plus chest compressions group, all had restoration of spontaneous circulation and seven survived (restoration of spontaneous circulation, p = .08). Neurologic outcome for (median and interquartile range) the control group included overall performance category score of 3, neurologic deficit score of 45%; for the emergency preservation and resuscitation group, overall performance category score was 3 (2-5) and neurologic deficit score was 45% (36; 50) and in the emergency preservation and resuscitation plus chest compressions group, overall performance category score was 2 (1-3) and neurologic deficit score was 13% (5; 21) (overall performance category score, p = .04; neurologic deficit score emergency preservation and resuscitation vs. emergency preservation and resuscitation plus chest compressions, p = .003). CONCLUSIONS: Emergency preservation and resuscitation by deep cerebral hypothermia combined with chest compressions during prolonged cardiac arrest in pigs are feasible and improve neurologic outcome.

Therapeutic hypothermia with a novel surface cooling device improves neurologic outcome after prolonged cardiac arrest in swine.

OBJECTIVE: Devices for rapid induction of mild hypothermia after cardiac arrest are needed. We hypothesized that the Life Recovery Systems' ThermoSuit System provides effective core cooling by pumping ice water over the skin surface and improves neurologic outcome after prolonged cardiac arrest. DESIGN: Prospective experimental study. SETTING: University research laboratory. SUBJECTS: Large White breed pigs (29 to 35 kg). INTERVENTIONS: Swine were anesthetized and mechanically ventilated. Ten minutes of untreated ventricular fibrillation, 3 mins of basic life support, and 5 mins of advanced cardiac life support, including two 0.4 IU/kg doses of vasopressin, were followed by up to three countershocks. After restoration of spontaneous circulation, swine were randomized to two groups (normothermic control, hypothermia). The hypothermia group was cooled from a pulmonary artery temperature of 38.5 +/- 0.5 degrees C to 33.0 degrees C and kept for 14 hrs. At day 9 of the experiment, overall performance categories scores (1, normal; 2, slightly disabled; 3, severely disabled; 4, comatose; 5, dead, brain dead) and neurologic deficit scores (0%, normal; 100%, brain dead) were assessed. Data are presented as median and interquartile range; group comparison was done with a Mann-Whitney U test. MEASUREMENTS AND MAIN RESULTS: In total, 16 of 22 animals were randomized. Time to target temperature in the hypothermia group (n = 8) was 9.0 (5.3-11.9) mins (cooling rate 0.4 [0.3-0.8] degrees C/min), and all animals achieved an overall performance categories score of 1. In the control group, one swine achieved an overall performance categories score of 1, three achieved a score of 2, and four achieved a score of 3 (p = .002). Neurologic deficit score was 0% (0%-4%) in the hypothermia group and 39% (19%-55%) in the control group (p = .001). No harmful side effects could be observed. CONCLUSIONS: The Life Recovery Systems' ThermoSuit System rapidly and safely induced mild therapeutic hypothermia. Hypothermia improved neurologic outcome in swine after cardiac arrest as compared with normothermia. Further studies are warranted to compare the device with established cooling methods.