Left-Ventricular Unloading With Impella During Refractory Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

OBJECTIVES: Extracorporeal cardiopulmonary resuscitation (ECPR) is the implementation of venoarterial extracorporeal membrane oxygenation (VA-ECMO) during refractory cardiac arrest. The role of left-ventricular (LV) unloading with Impella in addition to VA-ECMO ("ECMELLA") remains unclear during ECPR. This is the first systematic review and meta-analysis to characterize patients with ECPR receiving LV unloading and to compare in-hospital mortality between ECMELLA and VA-ECMO during ECPR. DATA SOURCES: Medline, Cochrane Central Register of Controlled Trials, Embase, and abstract websites of the three largest cardiology societies (American Heart Association, American College of Cardiology, and European Society of Cardiology). STUDY SELECTION: Observational studies with adult patients with refractory cardiac arrest receiving ECPR with ECMELLA or VA-ECMO until July 2023 according to the Preferred Reported Items for Systematic Reviews and Meta-Analysis checklist. DATA EXTRACTION: Patient and treatment characteristics and in-hospital mortality from 13 study records at 32 hospitals with a total of 1014 ECPR patients. Odds ratios (ORs) and 95% CI were computed with the Mantel-Haenszel test using a random-effects model. DATA SYNTHESIS: Seven hundred sixty-two patients (75.1%) received VA-ECMO and 252 (24.9%) ECMELLA. Compared with VA-ECMO, the ECMELLA group was comprised of more patients with initial shockable electrocardiogram rhythms (58.6% vs. 49.3%), acute myocardial infarctions (79.7% vs. 51.5%), and percutaneous coronary interventions (79.0% vs. 47.5%). VA-ECMO alone was more frequently used in pulmonary embolism (9.5% vs. 0.7%). Age, rate of out-of-hospital cardiac arrest, and low-flow times were similar between both groups. ECMELLA support was associated with reduced odds of mortality (OR, 0.53 [95% CI, 0.30-0.91]) and higher odds of good neurologic outcome (OR, 2.22 [95% CI, 1.17-4.22]) compared with VA-ECMO support alone. ECMELLA therapy was associated with numerically increased but not significantly higher complication rates. Primary results remained robust in multiple sensitivity analyses. CONCLUSIONS: ECMELLA support was predominantly used in patients with acute myocardial infarction and VA-ECMO for pulmonary embolism. ECMELLA support during ECPR might be associated with improved survival and neurologic outcome despite higher complication rates. However, indications and frequency of ECMELLA support varied strongly between institutions. Further scientific evidence is urgently required to elaborate standardized guidelines for the use of LV unloading during ECPR.

Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study.

BACKGROUND: Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome. METHODS: This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan-Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality. RESULTS: A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow-Pittsburgh Cerebral Performance Categories 1-2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18-1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03-1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12-1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16-1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52-0.76). CONCLUSIONS: A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

Influence of long-term treatment with glyceryl trinitrate on remote ischemic conditioning.

Remote ischemic conditioning (RIC) protects against sustained myocardial ischemia. Because of overlapping mechanisms, this protection may be altered by glyceryl trinitrate (GTN), which is commonly used in the treatment of patients with chronic ischemic heart disease. We investigated whether long-term GTN treatment modifies the protection by RIC in the rat myocardium and human endothelium. We studied infarct size (IS) in rat hearts subjected to global ischemia-reperfusion (I/R) in vitro and endothelial function in healthy volunteers subjected to I/R of the upper arm. In addition to allocated treatment, rats were coadministered with reactive oxygen species (ROS) or nitric oxide (NO) scavengers. Rats and humans were randomized to 1) control, 2) RIC, 3) GTN, and 4) GTN + RIC. In protocols 3 and 4, rats and humans underwent long-term GTN treatment for 7 consecutive days, applied subcutaneously or 2 h daily transdermally. In rats, RIC and long-term GTN treatment reduced mean IS (18 ± 12%, P = 0.007 and 15 ± 5%, P = 0.002) compared with control (35 ± 13%). RIC and long-term GTN treatment in combination did not reduce IS (29 ± 12%, P = 0.55 vs. control). ROS and NO scavengers both attenuated IS reduction by RIC and long-term GTN treatment. In humans, I/R reduced endothelial function ( P = 0.01 vs. baseline). Separately, RIC and long-term GTN prevented the reduction in endothelial function caused by I/R; given in combination, prevention was lost. RIC and long-term GTN treatment both protect against rat myocardial and human endothelial I/R injury through ROS and NO-dependent mechanisms. However, when given in combination, RIC and long-term GTN treatment fail to confer protection. NEW & NOTEWORTHY Remote ischemic conditioning (RIC) and long-term glyceryl trinitrate (GTN) treatment protect against ischemia-reperfusion injury in both human endothelium and rat myocardium. However, combined application of RIC and long-term GTN treatment abolishes the individual protective effects of RIC and GTN treatment on ischemia-reperfusion injury, suggesting an interaction of clinical importance.

Return to Work After Refractory Out-of-Hospital Cardiac Arrest in Patients Managed With or Without Extracorporeal Cardiopulmonary Resuscitation: A Nationwide Register-Based Study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used for refractory out-of-hospital cardiac arrest (OHCA). However, survivors managed with ECPR are at risk of poor functional status. The purpose of this study was to investigate return to work (RTW) after refractory OHCA. METHODS AND RESULTS: Of 44 360 patients with OHCA in the period of 2011 to 2020, this nationwide registry-based study included 805 patients with refractory OHCA in the working age (18-65 years) who were employed before OHCA (2% of the total OHCA cohort). Demographics, prehospital characteristics, status at hospital arrival, employment status, and survival were retrieved through the Danish national registries. Sustainable RTW was defined as RTW for ≥6 months without any long sick leave relapses. Median follow-up time was 4.1 years. ECPR and standard advanced cardiovascular life support were applied in 136 and 669 patients, respectively. RTW 1 year after OHCA was similar (39% versus 54%; P=0.2) and sustainable RTW was high in both survivors managed with ECPR and survivors managed with standard advanced cardiovascular life support (83% versus 85%; P>0.9). Younger age and shorter length of hospitalization were associated with RTW in multivariable Cox analysis, whereas ECPR was not. CONCLUSIONS: In refractory OHCA-patients employed prior to OHCA, approximately 1 out of 2 patients were employed after 1 year with no difference between patients treated with ECPR or standard advanced cardiovascular life support. Younger age and shorter length of hospitalization were associated with RTW while ECPR was not.

Effect of venoarterial extracorporeal membrane oxygenation initiation timing on tricuspid valve surgery outcomes.

Objectives: Tricuspid valve surgery is associated with high rates of shock and in-hospital mortality. Early initiation of venoarterial extracorporeal membrane oxygenation after surgery may provide right ventricular support and improve survival. We evaluated mortality in patients undergoing tricuspid valve surgery based on the timing of venoarterial extracorporeal membrane oxygenation. Methods: All consecutive adult patients undergoing isolated or combined surgical tricuspid valve repair or replacement from 2010 to 2022 requiring venoarterial extracorporeal membrane oxygenation use were stratified by initiation in the operating room (Early) versus outside of the operating room (Late). Variables associated with in-hospital mortality were explored using logistic regression. Results: There were 47 patients who required venoarterial extracorporeal membrane oxygenation: 31 Early and 16 Late. Mean age was 55.6 years (standard deviation, 16.8), 25 (54.3%) were in New York Heart Association class III/IV, 30 (60.8%) had left-sided valve disease, and 11 (23.4%) had undergone prior cardiac surgery. Median left ventricular ejection fraction was 60.0% (interquartile range, 45-65), right ventricular size was moderately to severely increased in 26 patients (60.5%), and right ventricular function was moderately to severely reduced in 24 patients (51.1%). Concomitant left-sided valve surgery was performed in 25 patients (53.2%). There were no differences in baseline characteristics or invasive measurements immediately before surgery between the Early and Late groups. Venoarterial extracorporeal membrane oxygenation was initiated 194 (23.0-840.0) minutes after cardiopulmonary bypass in the Late venoarterial extracorporeal membrane oxygenation group. In-hospital mortality was 35.5% (n = 11) in the Early group versus 68.8% (n = 11) in the Late group (P = .037). Late venoarterial extracorporeal membrane oxygenation was associated with in-hospital mortality (odds ratio, 4.00; 1.10-14.50; P = .035). Conclusions: Early postoperative initiation of venoarterial extracorporeal membrane oxygenation after tricuspid valve surgery in high-risk patients may be associated with improvement in postoperative hemodynamics and in-hospital mortality.

Selection of patients for mechanical circulatory support for refractory out-of-hospital cardiac arrest.

OBJECTIVE: To describe characteristics of patients admitted with refractory cardiac arrest for possible extracorporeal cardiopulmonary resuscitation (ECPR) and gain insight into the reasons for refraining from treatment in some. METHODS: Nationwide retrospective cohort study involving all tertiary centres providing ECPR in Denmark. Consecutive patients admitted with ongoing chest compression for evaluation for ECPR treatment were enrolled. Presenting characteristics, duration of no-flow and low-flow time, end-tidal carbon dioxide (ETCO2), lactate and pH, and recording of reasons for refraining from ECPR documented by the treating team were recorded. Outcomes were survival to intensive care unit admission and survival to hospital discharge. RESULTS: Of 579 patients admitted with refractory cardiac arrest for possible ECPR, 221 patients (38%) proceeded to ECPR and 358 patients (62%) were not considered candidates. Median prehospital low-flow time was 70 min (IQR 56 to 85) in ECPR patients and 62 min (48 to 81) in no-ECPR patients, p<0.001. Intra-arrest transport was more than 50 km in 92 (42%) ECPR patients and 135 in no-ECPR patients (38%), p=0.25. The leading causes for not initiating ECPR stated by the treating team were duration of low-flow time in 39%, severe metabolic derangement in 35%, and in 31% low ETCO2. The prevailing combination of contributing factors were non-shockable rhythm, low ETCO2, and metabolic derangement or prehospital low-flow time combined with low ETCO2. Survival to discharge was only achieved in six patients (1.7%) in the no-ECPR group. CONCLUSIONS: In this large nationwide study of patients admitted for possible ECPR, two-thirds of patients were not treated with ECPR. The most frequent reasons to abstain from ECPR were long duration of prehospital low-flow time, metabolic derangement and low ETCO2.

Survival and neurological outcome after out-of-hospital cardiac arrest treated with and without mechanical circulatory support.

Aim: The aim of this study was to describe the survival and neurological outcome in patients with OHCA treated with and without mechanical circulatory support (MCS). Methods: This was a retrospective observational cohort study on patients with OHCA admitted to Aarhus University Hospital, Denmark, between January 2015 and December 2019. Kaplan-Meier estimates were used to evaluate 30-day and 30-180-day survival. Cox regression analysis was used to assess the association between covariates and one-year mortality. Results: Among 1,015 patients admitted, 698 achieved return of spontaneous circulation (ROSC) before admission, 101 patients with refractory OHCA received mechanical circulatory support (MCS) and the remaining 216 patients with refractory OHCA did not receive MCS treatment. Survival to hospital discharge was 47% (478/1015). Good neurological outcome defined as Cerebral Performance Categories 1-2 were seen among 92% (438/478) of the patients discharged from hospital. Median low-flow was 15 [8-22] minutes in the ROSC group and 105 [94-123] minutes in the MCS group. Mortality rates were high within the first 30 days, however; 30-180-day survival in patients discharged remained constant over time in both patients with ROSC on admission and patients admitted with MCS. Advanced age > 70 years (hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.11-3.49), pulseless electrical activity (HR 2.39, 95% CI 1.25-4.60) and asystole HR 2.70, 95% CI 1.25-5.95) as initial rhythms were associated with one-year mortality in patients with ROSC. Conclusions: Short-term survival rates were high among patients with ROSC and patients receiving MCS. Among patients who survived to day 30, landmark analyses showed comparable 180-day survival in the two groups despite long low-flow times in the MCS group. Advanced age and initial non-shockable rhythms were independent predictors of one-year mortality in patients with ROSC on admission.

[Treated prolonged cardiac arrest without severe cognitive impairment].

The cognitive function and quality of life after extracorporeal cardiopulmonary resuscitation (ECPR) remain uncertain. In this case report, a 61-year-old male underwent ECPR for refractory out-of-hospital cardiac arrest after 102 minutes of resuscitation. The cause of cardiac arrest was acute myocardial infarction, and occlusion of the left anterior descending artery was treated with balloon angioplasty. Five years later, the patient had preserved psychical and mental health, cognitive function, and good quality of life despite prolonged cardiopulmonary resuscitation.

Use of Helicopters to Reduce Health Care System Delay in Patients With ST-Elevation Myocardial Infarction Admitted to an Invasive Center.

Timely reperfusion in ST-elevation myocardial infarction (STEMI) is essential. This study aimed to evaluate the reduction in system delay (time from emergency medical service [EMS] call to primary percutaneous coronary intervention [PPCI]) in patients with STEMI when using helicopter EMS (HEMS) rather than ground-based EMS (GEMS). This was a retrospective, nationwide cohort study of consecutive patients with STEMI treated with PPCI at 5 PPCI centers in Denmark. Polynomial spline curves were constructed to describe the association between system delay and distance to the PPCI center stratified by transportation mode. A total of 26,433 patients with STEMI were treated with PPCI between January 1, 1999, and December 31, 2016. In 16,436 patients field triaged directly to the PPCI center, the proportion treated within 120 minutes of the EMS call was 75% for those living 0 to 25 km from the PPCI center compared with 65% for all patients transported by GEMS (median transport distance 50 km [interquartile range 23 to 90]) and 64% for all patients transported by HEMS (median transport distance 119 km [interquartile range 99 to 142]). The estimated reduction in system delay owed to using HEMS rather than GEMS was 14, 16, 20, and 29 minutes for patients living 75, 100, 125, and 170 km from a PPCI center. In conclusion, this study confirmed that using HEMS ensures that most patients with STEMI, living up to 170 km from a PPCI center, can be treated within 120 minutes of their EMS call provided they are field triaged directly to the PPCI center.

Extracorporeal cardiopulmonary resuscitation: a national study on the association between favourable neurological status and biomarkers of hypoperfusion, inflammation, and organ injury.

AIMS: In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischaemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR). We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR. METHODS AND RESULTS: This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011-2020). Biomarkers the first days after ECPR-initiation were assessed. Odds ratio of favourable neurological status (Cerebral Performance Category 1-2) at hospital discharge was estimated by logistic regression analyses. Cut-off values were calculated using the Youden's index. Fifty-six patients (25%) survived to hospital discharge, 51 (91%) with a favourable neurological status. Factors independently associated with favourable neurological status were low flow time <81 min, admission leukocytes ≥12.8 × 109/L, admission lactate <13.2 mmol/L, alkaline phosphatase (ALP) < 56 (day1) or <55 U/L (day2), and day 1 creatine kinase MB (CK-MB) < 500 ng/mL. Selected biomarkers (leukocytes, C-reactive protein, and lactate) were significantly better predictors of favourable neurological status than classic OHCA-variables (sex, age, low-flow time, witnessed arrest, shockable rhythm) alone (P = 0.001) after hospital admission. CONCLUSION: Biomarkers of hypoperfusion (lactate), inflammation (leucocytes), and organ injury (ALP and CK-MB) were independently associated with neurological status at hospital discharge. Biomarkers of hypoperfusion and inflammation (at hospital admission) and organ injury (days 1 and 2 after ECPR) may aid in the clinical decision of when to prolong or terminate ECPR in cases of refractory OHCA.

Giant unruptured aneurysm of the left coronary sinus of Valsalva presenting as acute coronary syndrome: a case report.

BACKGROUND: Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly that can be congenital or acquired. Unruptured aneurysms may be asymptomatic but can present as malignant arrhythmias, acute chest pain, and even sudden cardiac death. Both ruptured and unruptured SVAs may have fatal complications, thus prompt diagnosis and surgery is critical. CASE SUMMARY: We report a successful surgical repair of an unruptured aneurysm of the left sinus of Valsalva presenting as acute coronary syndrome. Coronary angiography (CAG) and cardiac multislice computed tomography (CT) revealed a large unruptured aneurysm of the left sinus of Valsalva. Surgical repair was performed by resection of the aneurysm, aortic valve replacement with composite graft, and coronary artery bypass. DISCUSSION: Aneurysm of the left sinus of Valsalva is an extremely rare condition. Correct diagnosis can be done by echocardiography, CAG, or CT. Non-ruptured aneurysms should be surgically repaired if they are associated with significant symptoms or if their size enlarge rapidly.