Different circulating biomarkers in women and men with paroxysmal atrial fibrillation: results from the AF-RISK and RACE V studies.

AIMS: The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF. METHODS AND RESULTS: Sex differences in 92 blood biomarkers were measured in 364 patients included in our discovery cohort, the identification of a risk profile to guide atrial fibrillation therapy (AF-RISK) study, assessed by multivariable logistic regression and enrichment pathway analysis. Findings were subsequently confirmed in 213 patients included in our validation cohort, the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study. In the discovery cohort, mean age was 59 ± 12 years, 41% were women. CHA2DS2-VASc-score was 1.6 ± 1.4. A total of 46% had hypertension, 10% diabetes, and 50% had heart failure, predominantly with preserved ejection fraction (47%). In women, activated leucocyte cell adhesion molecule (ALCAM) and fatty acid binding protein-4 (FABP-4) were higher. In men, matrix metalloproteinase-3 (MMP-3), C-C motif chemokine-16 (CCL-16), and myoglobin were higher. In the validation cohort, four out of five biomarkers could be confirmed: levels of ALCAM (P = 1.73 × 10-4) and FABP-4 (P = 2.46 × 10-7) and adhesion biological pathways [false discovery rate (FDR) = 1.23 × 10-8] were higher in women. In men, levels of MMP-3 (P = 4.31 × 10-8) and myoglobin (P = 2.10 × 10-4) and markers for extracellular matrix degradation biological pathways (FDR = 3.59 × 10-9) were higher. CONCLUSION: In women with paroxysmal AF, inflammatory biomarkers were more often higher, while in men with paroxysmal AF, biomarkers for vascular remodelling were higher. Our data support the clinical notion that pathophysiological mechanisms in women and men with AF may differ. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01510210 for AF-RISK; Clinicaltrials.gov NCT02726698 for RACE V.

Maximum-fixed energy shocks for cardioverting atrial fibrillation.

AIMS: Direct-current cardioversion is one of the most commonly performed procedures in cardiology. Low-escalating energy shocks are common practice but the optimal energy selection is unknown. We compared maximum-fixed and low-escalating energy shocks for cardioverting atrial fibrillation. METHODS AND RESULTS: In a single-centre, single-blinded, randomized trial, we allocated elective atrial fibrillation patients to cardioversion using maximum-fixed (360-360-360 J) or low-escalating (125-150-200 J) biphasic truncated exponential shocks. The primary endpoint was sinus rhythm 1 min after cardioversion. Safety endpoints were any arrhythmia, myocardial injury, skin burns, and patient-reported pain after cardioversion. We randomized 276 patients, and baseline characteristics were well-balanced between groups (mean ± standard deviation age: 68 ± 9 years, male: 72%, atrial fibrillation duration >1 year: 30%). Sinus rhythm 1 min after cardioversion was achieved in 114 of 129 patients (88%) in the maximum-fixed energy group, and in 97 of 147 patients (66%) in the low-escalating energy group (between-group difference; 22 percentage points, 95% confidence interval 13-32, P < 0.001). Sinus rhythm after first shock occurred in 97 of 129 patients (75%) in the maximum-fixed energy group compared to 50 of 147 patients (34%) in the low-escalating energy group (between-group difference; 41 percentage points, 95% confidence interval 30-51). There was no significant difference between groups in any safety endpoint. CONCLUSION: Maximum-fixed energy shocks were more effective compared with low-escalating energy shocks for cardioverting atrial fibrillation. We found no difference in any safety endpoint.

Elevated calprotectin in patients with atrial fibrillation with and without heart failure.

Calprotectin is an inflammatory marker, which has been found elevated in patients suffering from cardiac conditions, e.g. myocardial infarction, unstable angina and chronic heart failure. Inflammation has further been linked to atrial fibrillation (AF). However, the association between calprotectin and AF is unknown. We aimed to compare calprotectin levels in patients suffering from AF with healthy adults. In addition, AF patients with and without heart failure were compared. Calprotectin was measured in patients undergoing elective direct current cardioversion for AF. Calprotectin was determined before, 4 hours and 3 months after cardioversion. Healthy blood donors were used to verify the reference interval for calprotectin. In total, 104 prospectively enrolled patients were included. The median serum calprotectin level for AF patients was 1.6 µg/mL before cardioversion. Calprotectin levels increased significantly 4 h (1.9 µg/mL) and 3 months (2.2 µg/mL) after cardioversion. Blood donors' median serum calprotectin (1.3 µg/mL) was significantly lower than AF patients. AF patients with heart failure had significantly higher calprotectin at baseline compared with AF patients without a history of heart failure (2.0 µg/mL vs. 1.5 µg/mL). The difference was not significant at 4 h (2.0 µg/mL vs. 1.7 µg/mL) or 3 months (2.5 µg/mL vs. 2.2 µg/mL). In conclusion, the calprotectin levels in patients with AF were significantly higher than healthy blood donors and were further increased after cardioversion. AF patients with heart failure had significantly higher levels of calprotectin than AF patients without heart failure.

Why Do Not Physicians Attend Hospital Cardiopulmonary Resuscitation Training?

INTRODUCTION: Cardiopulmonary resuscitation (CPR) training is mandatory in most hospitals. Despite this, some hospital staff do not attend CPR training on a regular basis, but the barriers to training attendance are sparsely investigated. This study aimed to investigate CPR course attendance, barriers to participation, and possible initiatives to increase CPR course attendance. METHODS: Physicians from one university hospital and one regional hospital in the Central Denmark Region were included. Questionnaires were handed out at daily staff meetings at departments of internal medicine and surgery. RESULTS: In total, 233 physicians responded (response rate: 92%, male: 54%). Overall, 32% of physicians had not attended CPR training at the hospital. Mean (±standard deviation) time since the last CPR course participation was 17 (±3) months. Frequent barriers to attending courses included not knowing when courses are conducted (70%) and where to sign up for training (45%). The majority (60%) of physicians responded that the reason why they prioritize course participation is to be professionally updated. In contrast, 16% stated that they had sufficient CPR skills and therefore CPR training was unnecessary. Physicians stated that the following factors would improve CPR training participation: an annual day protected (no clinical work) for course attendance (72%), use of short booster sessions (49%), shorter courses combined with e-learning (51%) and shorter courses held over 2 days (46%). CONCLUSION: One-third of physicians did not attend hospital CPR training at two Danish hospitals. Several barriers to course participation exist, of which course registration seems to be a crucial factor. Alternative CPR training methods may help improve training participation.

Barriers and facilitators for in-hospital resuscitation: A prospective clinical study.

INTRODUCTION: Guideline deviations with impact on patient outcomes frequently occur during in-hospital cardiopulmonary resuscitation (CPR). However, barriers and facilitators for preventing these guideline deviations are understudied. We aimed to characterize challenges occurring during IHCA and identify barriers and facilitators perceived by actual team members immediately following IHCA events. METHODS: This was a prospective multicenter clinical study. Following each resuscitation attempt in 6 hospitals over a 4-year period, we immediately sent web-based structured questionnaires to all responding team members, reporting their perceived resuscitation quality, teamwork, and communication and what they perceived as barriers or facilitators. Comments were analyzed using qualitative inductive thematic analysis methodology. RESULTS: We identified 924 resuscitation attempts and 3,698 survey responses were collected including 2,095 qualitative comments (response rate: 65%). Most frequent challenges were overcrowding (27%) and poor ergonomics/choreography of people in the room (17%). Narrative comments aligned into 24 unique barrier and facilitator themes in 4 domains: 6 related to treatment (most prevalent: CPR, rhythm check, equipment), 7 for teamwork (most prevalent: role allocation, crowd control, collaboration with ward staff), 6 for leadership (most prevalent: visible and distinct leader, multiple leaders, leader experience), and 5 for communication (most prevalent: closed loops, atmosphere in room, speaking loud/clear). CONCLUSION: Using novel, immediate after-event survey methodology of individual cardiac arrest team members, we characterized challenges and identified 24 themes within 4 domains that were barriers and facilitators for in-hospital resuscitation teams. We believe this level of detail is necessary to contextualize guidelines and training to facilitate high-quality resuscitation.

Decision-making in cardiac arrest: physicians' and nurses' knowledge and views on terminating resuscitation.

INTRODUCTION: Many cardiopulmonary resuscitation (CPR) attempts are unsuccessful and must be terminated. On the contrary, premature termination results in a self-fulfilling prophecy. This study aimed to investigate 1) physicians' self-assessed competence in terminating CPR, 2) physicians' and nurses' knowledge of the European Resuscitation Council guidelines on termination, and 3) single factors leading to termination. METHODS: Questionnaires were distributed at advanced cardiac life support (ACLS) courses at a university hospital in Denmark. Participants included ACLS health care providers, ie, physicians and nurses from cardiac arrest teams, intensive care and anesthetic units or medical wards with a duty to provide ACLS. Physicians were divided into junior physicians (house officers) and experienced physicians (specialist registrars and consultants). RESULTS: Overall, 308 participants responded (104 physicians and 204 nurses, response rate: 98%). Among physicians, 37 (36%) did not feel competent to decide when to terminate CPR (junior physicians: n=16, 64%, compared with experienced physicians: n=21, 28%, P=0.002). Two (2%) physicians and one (0.5%) nurse were able to state the contents of termination guidelines. Several factors were reported to impact termination, including absence of a pupillary light reflex (physicians: 17%, nurses: 22%) and cardiac standstill on echocardiography (physicians: 18%, nurses: 20%). Moreover, nine (9%) physicians and 35 (17%) nurses would terminate prolonged CPR despite a shockable rhythm present. CONCLUSION: One-third of all physicians did not feel competent to decide when to terminate CPR. Physicians' and nurses' knowledge of termination guidelines was poor, and both professions reported unvalidated or controversial factors as a single reason for terminating CPR.

Clinical experience and skills of physicians in hospital cardiac arrest teams in Denmark: a nationwide study.

BACKGROUND: The quality of in-hospital resuscitation is poor and may be affected by the clinical experience and cardiopulmonary resuscitation (CPR) training. This study aimed to investigate the clinical experience, self-perceived skills, CPR training and knowledge of the guidelines on when to abandon resuscitation among physicians of cardiac arrest teams. METHODS: We performed a nationwide cross-sectional study in Denmark. Telephone interviews were conducted with physicians in the cardiac arrest teams in public somatic hospitals using a structured questionnaire. RESULTS: In total, 93 physicians (53% male) from 45 hospitals participated in the study. Median age was 34 (interquartile range: 30-39) years. Respondents were medical students working as locum physicians (5%), physicians in training (79%) and consultants (16%), and the median postgraduate clinical experience was 48 (19-87) months. Most respondents (92%) felt confident in treating a cardiac arrest, while fewer respondents felt confident in performing intubation (41%) and focused cardiac ultrasound (39%) during cardiac arrest. Median time since last CPR training was 4 (2-10) months, and 48% had attended a European Resuscitation Council (ERC) Advanced Life Support course. The majority (84%) felt confident in terminating resuscitation; however, only 9% were able to state the ERC guidelines on when to abandon resuscitation. CONCLUSION: Physicians of Danish cardiac arrest teams are often inexperienced and do not feel competent performing important clinical skills during resuscitation. Less than half have attended an ERC Advanced Life Support course, and only very few physicians know the ERC guidelines on when to abandon resuscitation.

Cardioversion Efficacy Using Pulsed Biphasic or Biphasic Truncated Exponential Waveforms: A Randomized Clinical Trial.

BACKGROUND: Several different defibrillators are currently used for cardioversion and defibrillation of cardiac arrhythmias. The efficacy of a novel pulsed biphasic (PB) waveform has not been compared to other biphasic waveforms. Accordingly, this study aims to compare the efficacy and safety of PB shocks with biphasic truncated exponential (BTE) shocks in patients undergoing cardioversion of atrial fibrillation or -flutter. METHODS AND RESULTS: This prospective, randomized study included patients admitted for elective direct current cardioversion. Patients were randomized to receive cardioversion using either PB or BTE shocks. We used escalating shocks until sinus rhythm was obtained or to a maximum of 4 shocks. Patients randomized to PB shocks received 90, 120, 150, and 200 J and patients randomized to BTE shocks received 100, 150, 200, and 250 J, as recommended by the manufacturers. In total, 69 patients (51%) received PB shocks and 65 patients (49%) BTE shocks. Successful cardioversion, defined as sinus rhythm 4 hours after cardioversion, was achieved in 43 patients (62%) using PB shocks and in 56 patients (86%) using BTE shocks; ratio 1.4 (95% CI 1.1-1.7) (P=0.002). There was no difference in safety (ie, myocardial injury judged by changes in high-sensitive troponin I levels; ratio 1.1) (95% CI 1.0-1.3), P=0.15. The study was terminated prematurely because of an adverse event. CONCLUSIONS: Cardioversion using a BTE waveform was more effective when compared with a PB waveform. There was no difference in safety between the 2 waveforms, as judged by changes in troponin I levels. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02317029.

Hospital implementation of resuscitation guidelines and review of CPR training programmes: a nationwide study.

This study aimed to investigate cardiopulmonary resuscitation (CPR) guideline implementation and CPR training in hospitals. This nationwide study included mandatory resuscitation protocols from each Danish hospital. Protocols were systematically reviewed for adherence to the European Resuscitation Council (ERC) 2010 guidelines and CPR training in each hospital. Data were included from 45 of 47 hospitals. Adherence to the ERC basic life support (BLS) algorithm was 49%, whereas 63 and 58% of hospitals adhered to the recommended chest compression depth and rate. Adherence to the ERC advanced life support (ALS) algorithm was 81%. Hospital BLS course duration was [median (interquartile range)] 2.3 (1.5-2.5) h, whereas ALS course duration was 4.0 (2.5-8.0) h. Implementation of ERC 2010 guidelines on BLS is limited in Danish hospitals 2 years after guideline publication, whereas the majority of hospitals adhere to the ALS algorithm. CPR training differs among hospitals.