Atrial Fibrillation Detection With an Analog Smartwatch: Prospective Clinical Study and Algorithm Validation.

BACKGROUND: Atrial fibrillation affects approximately 4% of the world's population and is one of the major causes of stroke, heart failure, sudden death, and cardiovascular morbidity. It can be difficult to diagnose when asymptomatic or in the paroxysmal stage, and its natural history is not well understood. New wearables and connected devices offer an opportunity to improve on this situation. OBJECTIVE: We aimed to validate an algorithm for the automatic detection of atrial fibrillation from a single-lead electrocardiogram taken with a smartwatch. METHODS: Eligible patients were recruited from 4 sites in Paris, France. Electrocardiograms (12-lead reference and single lead) were captured simultaneously. The electrocardiograms were reviewed by independent, blinded board-certified cardiologists. The sensitivity and specificity of the algorithm to detect atrial fibrillation and normal sinus rhythm were calculated. The quality of single-lead electrocardiograms (visibility and polarity of waves, interval durations, heart rate) was assessed in comparison with the gold standard (12-lead electrocardiogram). RESULTS: A total of 262 patients (atrial fibrillation: n=100, age: mean 74.3 years, SD 12.3; normal sinus rhythm: n=113, age: 61.8 years, SD 14.3; other arrhythmia: n=45, 66.9 years, SD 15.2; unreadable electrocardiograms: n=4) were included in the final analysis; 6.9% (18/262) were classified as Noise by the algorithm. Excluding other arrhythmias and Noise, the sensitivity for atrial fibrillation detection was 0.963 (95% CI lower bound 0.894), and the specificity was 1.000 (95% CI lower bound 0.967). Visibility and polarity accuracies were similar (1-lead electrocardiogram: P waves: 96.9%, QRS complexes: 99.2%, T waves: 91.2%; 12-lead electrocardiogram: P waves: 100%, QRS complexes: 98.8%, T waves: 99.5%). P-wave visibility accuracy was 99% (99/100) for patients with atrial fibrillation and 95.7% (155/162) for patients with normal sinus rhythm, other arrhythmias, and unreadable electrocardiograms. The absolute values of the mean differences in PR duration and QRS width were <3 ms, and more than 97% were <40 ms. The mean difference between the heart rates from the 1-lead electrocardiogram calculated by the algorithm and those calculated by cardiologists was 0.55 bpm. CONCLUSIONS: The algorithm demonstrated great diagnostic performance for atrial fibrillation detection. The smartwatch's single-lead electrocardiogram also demonstrated good quality for physician use in daily routine care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04351386; http://clinicaltrials.gov/ct2/show/NCT04351386.

Low-dose corticosteroid therapy for cardiogenic shock in adults (COCCA): study protocol for a randomized controlled trial.

BACKGROUND: Cardiogenic shock (CS) is a life-threatening condition characterized by circulatory insufficiency caused by an acute dysfunction of the heart pump. The pathophysiological approach to CS has recently been enriched by the tissue consequences of low flow, including inflammation, endothelial dysfunction, and alteration of the hypothalamic-pituitary-adrenal axis. The aim of the present trial is to evaluate the impact of early low-dose corticosteroid therapy on shock reversal in adults with CS. METHOD/DESIGN: This is a multicentered randomized, double-blind, placebo-controlled trial with two parallel arms in adult patients with CS recruited from medical, cardiac, and polyvalent intensive care units (ICU) in France. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 380 patients (190 per group). For the treatment group, hydrocortisone (50 mg intravenous bolus every 6 h) and fludrocortisone (50 µg once a day enterally) will be administered for 7 days or until discharge from the ICU. The primary endpoint is catecholamine-free days at day 7. Secondary endpoints include morbidity and all-cause mortality at 28 and 90 days post-randomization. Pre-defined subgroups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use, and adrenal profiles according the short corticotropin stimulation test. Each patient will be followed for 90 days. All analyses will be conducted on an intention-to-treat basis. DISCUSSION: This trial will provide valuable evidence about the effectiveness of low dose of corticosteroid therapy for CS. If effective, this therapy might improve outcome and become a therapeutic adjunct for patients with CS. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03773822 . Registered on 12 December 2018.

Extracorporeal membrane oxygenation network organisation and clinical outcomes during the COVID-19 pandemic in Greater Paris, France: a multicentre cohort study.

BACKGROUND: In the Île-de-France region (henceforth termed Greater Paris), extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) was considered early in the COVID-19 pandemic. We report ECMO network organisation and outcomes during the first wave of the pandemic. METHODS: In this multicentre cohort study, we present an analysis of all adult patients with laboratory-confirmed SARS-CoV-2 infection and severe ARDS requiring ECMO who were admitted to 17 Greater Paris intensive care units between March 8 and June 3, 2020. Central regulation for ECMO indications and pooling of resources were organised for the Greater Paris intensive care units, with six mobile ECMO teams available for the region. Details of complications (including ECMO-related complications, renal replacement therapy, and pulmonary embolism), clinical outcomes, survival status at 90 days after ECMO initiation, and causes of death are reported. Multivariable analysis was used to identify pre-ECMO variables independently associated with 90-day survival after ECMO. FINDINGS: The 302 patients included who underwent ECMO had a median age of 52 years (IQR 45-58) and Simplified Acute Physiology Score-II of 40 (31-56), and 235 (78%) of whom were men. 165 (55%) were transferred after cannulation by a mobile ECMO team. Before ECMO, 285 (94%) patients were prone positioned, median driving pressure was 18 cm H2O (14-21), and median ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen was 61 mm Hg (IQR 54-70). During ECMO, 115 (43%) of 270 patients had a major bleeding event, 27 of whom had intracranial haemorrhage; 130 (43%) of 301 patients received renal replacement therapy; and 53 (18%) of 294 had a pulmonary embolism. 138 (46%) patients were alive 90 days after ECMO. The most common causes of death were multiorgan failure (53 [18%] patients) and septic shock (47 [16%] patients). Shorter time between intubation and ECMO (odds ratio 0·91 [95% CI 0·84-0·99] per day decrease), younger age (2·89 [1·41-5·93] for ≤48 years and 2·01 [1·01-3·99] for 49-56 years vs ≥57 years), lower pre-ECMO renal component of the Sequential Organ Failure Assessment score (0·67, 0·55-0·83 per point increase), and treatment in centres managing at least 30 venovenous ECMO cases annually (2·98 [1·46-6·04]) were independently associated with improved 90-day survival. There was no significant difference in survival between patients who had mobile and on-site ECMO initiation. INTERPRETATION: Beyond associations with similar factors to those reported on ECMO for non-COVID-19 ARDS, 90-day survival among ECMO-assisted patients with COVID-19 was strongly associated with a centre's experience in venovenous ECMO during the previous year. Early ECMO management in centres with a high venovenous ECMO case volume should be advocated, by applying centralisation and regulation of ECMO indications, which should also help to prevent a shortage of resources. FUNDING: None.

Hemodynamic efficiency of hemodialysis treatment with high cut-off membrane during the early period of post-resuscitation shock: The HYPERDIA trial.

BACKGROUND: After resuscitation of cardiac arrest (CA), an acute circulatory failure occurs in about 50% of cases, which shares many characteristics with septic shock. Most frequently, supportive treatments are poorly efficient to prevent multiple organ failure and death. We evaluated whether an early plasma removal of inflammatory mediators using high cut-off continuous veno-venous hemodialysis (HCO-CVVHD) could improve hemodynamic status and outcome of these patients. PATIENTS AND METHODS: We performed a randomized open-label trial. Patients with post-cardiac arrest shock (defined as requirement of norepinephrine or epinephrine infusion > 1 mg/h) were included. The experimental group received 2 distinct sessions of HCO-CVVHD during the first 48 h following ICU admission. The control group received continuous veno-venous hemofiltration (CVVH) with standard membranes if needed. The primary endpoint was the delay to shock resolution asssessed by the length of catecholamine infusion. Number of vasopressors-free days at day 28, arterial blood pressure measures every 6-hours, daily fluid balance and mortality (ICU and day-28) were evaluated as secondary endpoints. RESULTS: 35 patients were included: 17 (median age 68.4, 59% male) in the HCO-CVVHD group and 18 (median age 66.3, 83% male) in the control group. Baseline characteristics did not differ between the two groups. Day-28 mortality rate was 64.7% and 72.2% in the HCO-CVVHD and control group, respectively (p = 0.72). Probability of vasopressors discontinuation over time was similar in the two groups (p for logrank test = 0.67). Number of day-28 catecholamine-free days was 25.1 [0, 26.5] and 24.5 [0, 26.2] in the HCO-CVVHD and control group, respectively (p = 0.65). No difference was observed regarding the daily-dose of vasopressors, arterial pressure profile and fluid balance. CONCLUSION: In cardiac arrest patients, HCO-CVVHD did not decrease the lenght of post-resuscitation shock and had no significant effect on hemodynamic profile. REGISTRATION: NCT00780299.

Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction.

BACKGROUND: Vasopressor agents could have certain specific effects in patients with cardiogenic shock (CS) after myocardial infarction, which may influence outcome. Although norepinephrine and epinephrine are currently the most commonly used agents, no randomized trial has compared their effects, and intervention data are lacking. OBJECTIVES: The goal of this paper was to compare in a prospective, double-blind, multicenter, randomized study, the efficacy and safety of epinephrine and norepinephrine in patients with CS after acute myocardial infarction. METHODS: The primary efficacy outcome was cardiac index evolution, and the primary safety outcome was the occurrence of refractory CS. Refractory CS was defined as CS with sustained hypotension, end-organ hypoperfusion and hyperlactatemia, and high inotrope and vasopressor doses. RESULTS: Fifty-seven patients were randomized into 2 study arms, epinephrine and norepinephrine. For the primary efficacy endpoint, cardiac index evolution was similar between the 2 groups (p = 0.43) from baseline (H0) to H72. For the main safety endpoint, the observed higher incidence of refractory shock in the epinephrine group (10 of 27 [37%] vs. norepinephrine 2 of 30 [7%]; p = 0.008) led to early termination of the study. Heart rate increased significantly with epinephrine from H2 to H24 while remaining unchanged with norepinephrine (p < 0.0001). Several metabolic changes were unfavorable to epinephrine compared with norepinephrine, including an increase in cardiac double product (p = 0.0002) and lactic acidosis from H2 to H24 (p < 0.0001). CONCLUSIONS: In patients with CS secondary to acute myocardial infarction, the use of epinephrine compared with norepinephrine was associated with similar effects on arterial pressure and cardiac index and a higher incidence of refractory shock. (Study Comparing the Efficacy and Tolerability of Epinephrine and Norepinephrine in Cardiogenic Shock [OptimaCC]; NCT01367743).

Determinants and significance of cerebral oximetry after cardiac arrest: A prospective cohort study.

AIM OF THE STUDY: To study the determinants and the evolution of cerebral oximetry determined by near-infrared spectroscopy after out-of-hospital cardiac arrest of cardiac origin during therapeutic hypothermia and rewarming, and to compare cerebral oximetry values between patients with good and bad prognosis. METHODS: In this prospective, non-interventional, single center study, all consecutive patients between 18 and 80 years admitted for out-of-hospital cardiac arrest (OHCA) with a no flow less than 10min, a low flow of less than 50min and a persistent coma after ROSC with Glasgow score equal or less than seven at baseline were included. RESULTS: Between February 2012 and January 2013, 43 patients were admitted for OHCA in our ICU. Twenty-two patients (51%) were discharged with no or minimal neurologic complications (CPC 1-2). Mortality rate in the ICU was 46.5%. Cerebral oximetry (rSO2) was correlated with temperature, heart rhythm, PaO2, hemoglobin, and mean arterial pressure. Mean rSO2 during the 48 first hours was not different between patients with good and bad neurologic outcomes, respectively, 61.8 (5.9) vs. 58.1 (8.8), P=0.13, as during the period of hypothermia. The minimal value of rSO2 during the first 48h was significantly different between patients with good prognosis and those with bad prognosis, respectively, 45.0 (6.8) vs. 31.7 (15.0), P=0.0009. CONCLUSIONS: In this prospective cohort of OHCA patients, main determinants of rSO2 were systemic variables. Monitoring of rSO2 does not allow discriminating patients with good or bad outcome, but could be useful for identifying vulnerable periods for the development of neurologic injury.

Is copeptin level associated with 1-year mortality after out-of-hospital cardiac arrest? Insights from the Paris registry*.

OBJECTIVES: The availability of circulating biomarkers that helps to identify early out-of-hospital cardiac arrest survivors who are at increased risk of long-term mortality remains challenging. Our aim was to prospectively study the association between copeptin and 1-year mortality in patients with out-of-hospital cardiac arrest admitted in a tertiary cardiac arrest center. DESIGN: Retrospective monocenter study. SETTING: Tertiary cardiac arrest center in Paris, France. PATIENTS: Copeptin was assessed at admission and day 3. Pre- and intrahospital factors associated with 1-year mortality were analyzed by multivariate Cox proportional analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred ninety-eight consecutive out-of-hospital cardiac arrest patients (70.3% male; median age, 60.2 yr [49.9-71.4]) were admitted in a tertiary cardiac arrest center in Paris (France). After multivariate analysis, higher admission copeptin was associated with 1-year mortality with a threshold effect (hazard ratio(5th vs 1st quintile) = 1.64; 95% CI, 1.05-2.58; p = 0.03). Day 3 copeptin was associated with 1-year mortality in a dose-dependent manner (hazard ratio(2nd vs 1st quintile) = 1.87; 95% CI, 1.00-3.49; p = 0.05; hazard ratio(3rd vs 1st quintile) = 1.92; 95% CI, 1.02-3.64; p = 0.04; hazard ratio(4th vs 1st quintile) = 2.12; 95% CI, 1.14-3.93; p = 0.02; and hazard ratio(5th vs 1st quintile) = 2.75; 95% CI, 1.47-5.15; p < 0.01; p for trend < 0.01). For both admission and day 3 copeptin, association with 1-year mortality existed for out-of-hospital cardiac arrest of cardiac origin only (p for interaction = 0.05 and < 0.01, respectively). When admission and day 3 copeptin were mutually adjusted, only day 3 copeptin remained associated with 1-year mortality in a dose-dependent manner (p for trend = 0.01). CONCLUSION: High levels of copeptin were associated with 1-year mortality independently from prehospital and intrahospital risk factors, especially in out-of-hospital cardiac arrest of cardiac origin. Day 3 copeptin was superior to admission copeptin: this could permit identification of out-of-hospital cardiac arrest survivors at increased risk of mortality and allow for close observation of such patients.

Is epinephrine during cardiac arrest associated with worse outcomes in resuscitated patients?

BACKGROUND: Although epinephrine is essential for successful return of spontaneous circulation (ROSC), the influence of this drug on recovery during the post-cardiac arrest phase is debatable. OBJECTIVES: This study sought to investigate the relationship between pre-hospital use of epinephrine and functional survival among patients with out-of-hospital cardiac arrest (OHCA) who achieved successful ROSC. METHODS: We included all patients with OHCA who achieved successful ROSC admitted to a cardiac arrest center from January 2000 to August 2012. Use of epinephrine was coded as yes/no and by dose (none, 1 mg, 2 to 5 mg, >5 mg). A favorable discharge outcome was coded using a Cerebral Performance Category 1 or 2. Analyses incorporated multivariable logistic regression, propensity scoring, and matching methods. RESULTS: Of the 1,556 eligible patients, 1,134 (73%) received epinephrine; 194 (17%) of these patients had a good outcome versus 255 of 422 patients (63%) in the nontreated group (p < 0.001). This adverse association of epinephrine was observed regardless of length of resuscitation or in-hospital interventions performed. Compared with patients who did not receive epinephrine, the adjusted odds ratio of intact survival was 0.48 (95% confidence interval [CI]: 0.27 to 0.84) for 1 mg of epinephrine, 0.30 (95% CI: 0.20 to 0.47) for 2 to 5 mg of epinephrine, and 0.23 (95% CI: 0.14 to 0.37) for >5 mg of epinephrine. Delayed administration of epinephrine was associated with worse outcome. CONCLUSIONS: In this large cohort of patients who achieved ROSC, pre-hospital use of epinephrine was consistently associated with a lower chance of survival, an association that showed a dose effect and persisted despite post-resuscitation interventions. These findings suggest that additional studies to determine if and how epinephrine may provide long-term functional survival benefit are needed.

Remote monitoring of patients with implantable cardioverter-defibrillators: can results from large clinical trials be transposed to clinical practice?

BACKGROUND: Remote monitoring (RM) is increasingly used to follow up patients with implantable cardioverter-defibrillators (ICDs). Randomized control trials provide evidence for the benefit of this intervention, but data for RM in daily clinical practice with multiple-brands and unselected patients is lacking. AIMS: To assess the effect of RM on patient management and clinical outcome for recipients of ICDs in daily practice. METHODS: We reviewed ICD recipients followed up at our institution in 2009 with RM or with traditional hospital only (HO) follow-up. We looked at the effect of RM on the number of scheduled ambulatory follow-ups and urgent unscheduled consultations, the time between onset of asymptomatic events to clinical intervention and the clinical effectiveness of all consultations. We also evaluated the proportion of RM notifications representing clinically relevant situations. RESULTS: We included 355 patients retrospectively (RM: n=144, HO: n=211, 76.9% male, 60.3±15.2 years old, 50.1% with ICDs for primary prevention and mean left ventricular ejection fraction 35.5±14.5%). Average follow-up was 13.5 months. The RM group required less scheduled ambulatory follow-up consultations (1.8 vs. 2.1/patient/year; P<0.0001) and a far lower median time between the onset of asymptomatic events and clinical intervention (7 vs. 76 days; P=0.016). Of the 784 scheduled ambulatory follow-up consultations carried out, only 152 (19.4%) resulted in therapeutic intervention or ICD reprogramming. We also found that the vast majority of RM notifications (61.9%) were of no clinical relevance. CONCLUSION: RM allows early management of asymptomatic events and a reduction in scheduled ambulatory follow-up consultations in daily clinical practice, without compromising safety, endorsing RM as the new standard of care for ICD recipients.

Blood glucose level and outcome after cardiac arrest: insights from a large registry in the hypothermia era.

INTRODUCTION: The influence of blood glucose (BG) level during the post-resuscitation period after out-of-hospital cardiac arrest (OHCA) is still debated. To evaluate the relationship between blood glucose level and outcome, we included the median glycemia and its maximal amplitude over the first 48 h following ICU admission in an analysis of outcome predictors. METHODS: We conducted a database study in a cardiac arrest center in Paris, France. Between 2006 and 2010, we included 381 patients who were all resuscitated from an OHCA. A moderate glycemic control was applied in all patients. The median glycemia and the largest change over the first 48 h were included in a multivariate analysis that was performed to determine parameters associated with a favorable outcome. RESULTS: Of the 381 patients, 136 (36 %) had a favorable outcome (CPC 1-2). Median BG level was 7.6 mmol/L (6.3-9.8) in patients with a favorable outcome compared to 9.0 mmol/L (IQR 7.1-10.6) for patients with an unfavorable outcome (p < 0.01). Median BG level variation was 7.1 (4.2-11) and 9.6 (5.9-13.6) mmol/L in patients with and without a favorable outcome, respectively (p < 0.01). In multivariate analysis, an increased median BG level over the first 48 h was found to be an independent predictor of poor issue [OR = 0.43; 95 % CI (0.24-0.78), p = 0.006]. Finally a progressive increase in median BG level was associated with a progressive increase in the proportion of patients with a poor outcome. CONCLUSION: We observed a relationship between high blood glucose level and outcome after cardiac arrest. These results suggest the need to test a strategy combining both control of glycemia and minimization of glycemic variations for its ability to improve post-resuscitation care.