Early unfractionated heparin treatment in patients with STEMI - trial design and rationale.

The early unfractionated heparin (UFH) treatment in patients with ST-elevation myocardial infarction (STEMI) is a single-center, open-label, randomized controlled trial. The study population are patients with STEMI that undergo primary percutaneous coronary intervention (PPCI). The trial was designed to investigate whether early administration of unfractionated heparin immediately after diagnosis of STEMI is beneficial in terms of patency of infarct-related coronary artery (IRA) when compared to established UFH administration at the time of coronary intervention. The patients will be randomized in 1:1 fashion in one of the two groups. The primary efficacy endpoint of the study is Thrombolysis in myocardial infarction (TIMI) flow grades 2 and 3 on diagnostic coronary angiography. Secondary outcome measures are: TIMI flow after PPCI, progression to cardiogenic shock, 30-day mortality, ST-segment resolution, highest Troponin I and Troponin I values at 24 hours. The safety outcome is bleeding complications. The study of early heparin administration in patients with STEMI will address whether pretreatment with UFH can increase the rate of spontaneous reperfusion of infarct-related coronary artery.

The design of the PRINCESS 2 trial: A randomized trial to study the impact of ultrafast hypothermia on complete neurologic recovery after out-of-hospital cardiac arrest with initial shockable rhythm.

BACKGROUND: Delayed hypothermia, initiated after hospital arrival, several hours after cardiac arrest with 8-10 hours to reach the target temperature, is likely to have limited impact on overall survival. However, the effect of ultrafast hypothermia, i.e., delivered intra-arrest or immediately after return of spontaneous circulation (ROSC), on functional neurologic outcome after out-of-hospital cardiac arrest (OHCA) is unclear. In two prior trials, prehospital trans-nasal evaporative intra-arrest cooling was safe, feasible and reduced time to target temperature compared to delayed cooling. Both studies showed trends towards improved neurologic recovery in patients with shockable rhythms. The aim of the PRINCESS2-study is to assess whether cooling, initiated either intra-arrest or immediately after ROSC, followed by in-hospital hypothermia, significantly increases survival with complete neurologic recovery as compared to standard normothermia care, in OHCA patients with shockable rhythms. METHODS/DESIGN: In this investigator-initiated, randomized, controlled trial, the emergency medical services (EMS) will randomize patients at the scene of cardiac arrest to either trans-nasal cooling within 20 minutes from EMS arrival with subsequent hypothermia at 33°C for 24 hours after hospital admission (intervention), or to standard of care with no prehospital or in-hospital cooling (control). Fever (>37,7°C) will be avoided for the first 72 hours in both groups. All patients will receive post resuscitation care and withdrawal of life support procedures according to current guidelines. Primary outcome is survival with complete neurologic recovery at 90 days, defined as modified Rankin scale (mRS) 0-1. Key secondary outcomes include survival to hospital discharge, survival at 90 days and mRS 0-3 at 90 days. In total, 1022 patients are required to detect an absolute difference of 9% (from 45 to 54%) in survival with neurologic recovery (80% power and one-sided α=0,025, ß=0,2) and assuming 2,5% lost to follow-up. Recruitment starts in Q1 2024 and we expect maximum enrolment to be achieved during Q4 2024 at 20-25 European and US sites. DISCUSSION: This trial will assess the impact of ultrafast hypothermia applied on the scene of cardiac arrest, as compared to normothermia, on 90-day survival with complete neurologic recovery in OHCA patients with initial shockable rhythm. TRIAL REGISTRATION: NCT06025123.

Coronary features across the spectrum of out-of-hospital cardiac arrest with ST-elevation myocardial infarction (CAD-OHCA study).

AIM: We hypothesized that adult patients with out-of-hospital cardiac arrest (OHCA) and ST-elevation myocardial infarction (STEMI) requiring prolonged resuscitation have more severe coronary artery disease (CAD) than those responding rapidly, and more severe CAD than patients with STEMI without OHCA. METHODS: Consecutive conscious and comatose OHCA patients with STEMI after reestablishment of spontaneous circulation (ROSC), and patients with refractory OHCA undergoing veno-arterial extracorporeal membrane oxygenation (E-CPR OHCA) were compared to STEMI without OHCA (STEMI no OHCA). CAD severity was assessed by a single physician blinded to the resuscitation method, time to ROSC and level of consciousness. RESULTS: Between 2016 and 2022, 71 conscious OHCA, 157 comatose OHCA, 50 E-CPR OHCA and 101 STEMI no OHCA underwent immediate coronary angiography. Acute culprit lesion was documented less often in OHCA (88.1% vs 97%; p = 0.009) but complete occlusion was more frequent (68.8% vs 58.4%; p = 0.038) than in STEMI no OHCA. SYNTAX score was 5.6 in STEMI no OHCA, 10.2 in conscious OHCA, 13.4 in comatose OHCA and 26.8 in E-CPR OHCA (p < 0.001). There was a linear correlation between SYNTAX score and delay to ROSC/ECMO initiation (r2 = 0.61; p < 0.001). Post PCI culprit TIMI 3 flow was comparable between the groups (≥86%). SYNTAX score was among independent predictors of 5-year survival which was significantly decreased in comatose OHCA (56.1%) and E-CPR OHCA (36.0%) compared to conscious OHCA (83.1%) and STEMI no OHCA (88.1%). CONCLUSION: Compared to STEMI no OHCA, OHCA was associated with increased incidence of acute coronary occlusion and more complex non culprit CAD which progressively increased from conscious OHCA to E-CPR OHCA. Severity of CAD was associated with increased delays to ROSC/ECMO initiation and decreased long term survival.

Coronary disease in refractory cardiac arrest undergoing resuscitation with extracorporeal membrane oxygenation.

AIMS: Because re-establishment of spontaneous circulation (ROSC) in patients with cardiac arrest is frequently not achieved by conventional cardiopulmonary resuscitation (C-CPR), selected patients may undergo resuscitation with extracorporeal membrane oxygenation (E-CPR). We compared angiographic features and percutaneous coronary intervention (PCI) between patients undergoing E-CPR and those with ROSC after C-CPR. METHODS AND RESULTS: Forty-nine consecutive E-CPR patients undergoing immediate coronary angiography admitted between August 2013 and August 2022 were matched to 49 patients with ROSC after C-CPR. Multivessel disease (69.4% vs. 34.7%; P = 0.001), ≥ 50% unprotected left main (ULM) stenosis (18.4% vs. 4.1%; P = 0.025), and ≥1 chronic total occlusion (CTO) (28.6% vs. 10.2%; P = 0.021) were more often documented in E-CPR group. There was no significant differences in the incidence, features, and distribution of acute culprit lesion which was present in >90%. Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) (27.6 vs. 13.4; P = 0.002) and GENSINI (86.2 vs. 46.0; P = 0.001) scores were increased in E-CPR group. Optimal cut-off predicting E-CPR was 19.75 for SYNTAX (sensitivity 74%, specificity 87%) and 60.50 (sensitivity 69%, specificity 75%) for GENSINI score. More lesions were treated (1.3 vs. 1.1 lesions/patient; P = 0.002) and stents implanted (2.0 vs. 1.3/patient; P < 0.001) in E-CPR group. Final TIMI three flow was comparable (88.6% vs. 95.7%; P = 0.196) but residual SYNTAX (13.6 vs. 3.1; P < 0.001) and GENSINI (36.7 vs. 10.9; P < 0.001) scores remained increased in E-CPR group. CONCLUSION: Extracorporeal membrane oxygenation patients have more multivessel disease, ULM stenosis, and CTO but similar incidence, features, and distribution of acute culprit lesion. Despite more complex PCI, revascularization is less complete.

Case report: Treatment of tachycardia-induced cardiogenic shock with permanent His bundle pacing and atrioventricular node ablation.

Tachycardia-induced cardiomyopathy (T-CMP) related to supraventricular arrhythmia is a rare and often unrecognized cause of refractory cardiogenic shock. When rhythm control interventions are ineffective or no longer pursued, atrioventricular node ablation (AVNA) with pacemaker implantation is indicated. Conduction system pacing provides normal synchronous activation of the ventricles after AVNA. However, there is a lack of data on pace and ablate strategy in hemodynamically unstable patients. We report on 2 patients with T-CMP presenting with refractory cardiogenic shock who were successfully treated with His bundle pacing in conjunction with AVNA.

Long-Term Survival and Quality of Life in Non-Surgical Adult Patients Supported with Veno-Arterial Extracorporeal Oxygenation.

BACKGROUND: The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for hemodynamic support is on the rise. Not much is known about the impact of extracorporeal membrane oxygenation (ECMO) and its complications on long-term survival and quality of life. METHODS: In this single-center, cross-sectional study, we evaluated the survival and quality of life in patients treated with VA ECMO between May 2009 and July 2019. Follow-up was conducted between November 2019 and January 2020. RESULTS: Overall, 118 patients were evaluated in this study. Of the 37 patients who were alive at hospital discharge, 32 answered the EuroQol-5 dimensional-5-level questionnaire (EQ-5D-5L). For patients discharged alive from the hospital, mean survival was 8.1 years, 8.4 years for cardiogenic shock, and 5.0 years for patients with refractory cardiac arrest. EQ-5D-5L index value of ECMO survivors was not significantly different from the general age-matched population. Neurologic complications and major bleeding during index hospitalization limit long-term quality of life. CONCLUSIONS: Patients treated with VA ECMO have high in-hospital mortality, with extracorporeal membrane oxygenation cardio-pulmonary resuscitation patients being at higher risk of early death. However, once discharged from the hospital, most patients remain alive with a reasonable quality of life.

Longitudinal Analysis of Antiphospholipid Antibody Dynamics after Infection with SARS-CoV-2 or Vaccination with BNT162b2.

Antiphospholipid antibodies (aPL) comprise a group of autoantibodies that reflect prothrombotic risk in antiphospholipid syndrome (APS) but may also be present in a small proportion of healthy individuals. They are often transiently elevated in infections, including SARS-CoV-2, and may also be associated with vaccine-induced autoimmunity. Therefore, we aimed to investigate the dynamics of aPL in COVID-19 patients and in individuals (healthcare professionals-HCPs) after receiving BNT162b2 vaccine and to compare aPL levels and positivity with those found in APS patients. We measured solid-phase identifiable aPL, including anticardiolipin (aCL), anti-ß2 glycoprotein I (anti-ß2GPI), and anti-prothrombin/phosphatidylserine (aPS/PT) antibodies in 58 HCPs before and after vaccination (at 3 weeks, 3, 6, and 9 months after the second dose, and 3 weeks after the third booster dose), in 45 COVID-19 patients hospitalized in the ICU, in 89 COVID-19 patients hospitalized in the non-ICU (at admission, at hospital discharge, and at follow-up), and in 52 patients with APS. The most frequently induced aPL in COVID-19 patients (hospitalized in non-ICU) were aCL (50.6% of patients had positive levels at at least one time point), followed by anti-ß2GPI (21.3% of patients had positive levels at at least one time point). In 9/89 COVID-19 patients, positive aPL levels persisted for three months. One HCP developed aCL IgG after vaccination but the persistence could not be confirmed, and two HCPs developed persistent anti-ß2GPI IgG after vaccination with no increase during a 1-year follow-up period. Solid-phase aPL were detected in 84.6% of APS patients, in 49.4% of COVID-19 patients hospitalized in the non-ICU, in 33.3% of COVID-19 patients hospitalized in the ICU, and in only 17.2% of vaccinated HCPs. aPL levels and multiple positivity were significantly lower in both infected groups and in vaccinated individuals compared with APS patients. In conclusion, BNT162b2 mRNA vaccine may have induced aPL in a few individuals, whereas SARS-CoV-2 infection itself results in a higher percentage of aPL induction, but the levels, persistence, and multiple positivity of aPL do not follow the pattern observed in APS.

Percutaneous mechanical circulatory support from the collaborative multicenter Mechanical Unusual Support in TAVI (MUST) Registry.

OBJECTIVES: To evaluate the use and outcomes of percutaneous mechanical circulatory support (pMCS) utilized during transcatheter aortic valve implantation (TAVI) from high-volume centers. METHODS AND RESULTS: Our international multicenter registry including 13 high-volume TAVI centers with 87 patients (76.5 ± 11.8 years, 63.2% men) who underwent TAVI for severe aortic stenosis and required pMCS (75.9% VA-ECMO, 19.5% Impella CP, 4.6% TandemHeart) during the procedure (prior to TAVI 39.1%, emergent rescue 50.6%, following TAVI 10.3%). The procedures were considered high-risk, with 50.6% having severe left ventricular dysfunction, 24.1% biventricular dysfunction, and 32.2% severe pulmonary hypertension. In-hospital and 1-year mortality were 27.5% and 49.4%, respectively. Patients with prophylactic hemodynamic support had lower periprocedural mortality compared to patients with rescue insertion of pMCS (log rank = 0.013) and patients who did not undergo cardiopulmonary resuscitation during the TAVI procedure had better short and long term survival (log rank <0.001 and 0.015, respectively). CONCLUSIONS: Given the overall survival rate and low frequency of pMCS-related complications, our study results support the use of pMCS prophylactically or during the course of TAVI (bailout) in order to improve clinical outcomes in high-risk procedures or in case of acute life-threatening hemodynamic collapse.

Emergency veno-arterial extracorporeal membrane oxygenation (VA ECMO)-supported percutaneous interventions in refractory cardiac arrest and profound cardiogenic shock.

AIMS: We investigated the spectrum of emergency veno-arterial extracorporeal membrane oxygenation (VA ECMO)-supported interventions including percutaneous coronary intervention (PCI), transcatheter aortic valve implantation (TAVI) and invasive electrophysiology (EP). METHODS AND RESULTS: Between June 2010 and February 2020, 52 consecutive patients underwent VA ECMO implantation for refractory cardiac arrest (E-CPR) and 78 for profound cardiogenic shock. Percutaneous interventions on VA ECMO included PCI (n = 29), TAVI (n = 4) and EP (n = 1). Surgical interventions were cardiac (n = 36) or non-cardiac (n = 5). During PCI, ECMO flow was maintained at 2.7 ±â€¯1.0 L/min. Of the 40 treated lesions, 48% were located on left anterior descending and 20% on the left main artery. An average 2.0 ±â€¯1.8 DES/patient with diameter 3.2 ±â€¯0.5 mm and stented length 41 ±â€¯35 mm were implanted. PCI success was 83%. TAVI was performed in 4 patients with left ventricular ejection fraction 21 ±â€¯10% and mean aortic valve gradient 41 ±â€¯5 mmHg. After successful valve implantation supported by 1.4 ±â€¯0.1 L/min ECMO flow, mean gradient decreased to 11 ±â€¯5 mmHg without significant aortic regurgitation. In one patient radiofrequency ablation of His bundle followed by permanent pacemaker implantation was performed under ECMO flow of 2.8 L/min. Overall survival to hospital discharge with good neurological recovery was 29% in E-CPR and 44% in profound cardiogenic shock. CONCLUSIONS: Our study showed feasibility and effectiveness of VA ECMO-supported percutaneous interventions in patients with profound hemodynamic collapse.

Randomized Pilot Clinical Trial of Early Coronary Angiography Versus No Early Coronary Angiography After Cardiac Arrest Without ST-Segment Elevation: The PEARL Study.

BACKGROUND: The benefit of emergency coronary angiography after resuscitation from out-of-hospital cardiac arrest is uncertain for patients without ST-segment elevation. The aim of this randomized trial was to evaluate the efficacy and safety of early coronary angiography and to determine the prevalence of acute coronary occlusion in resuscitated patients with out-of-hospital cardiac arrest without ST-segment elevation. METHODS: Adult (>18 years) comatose survivors without ST-segment elevation after resuscitation from out-of-hospital cardiac arrest were prospectively randomized in a 1:1 fashion under exception to informed consent regulations to early coronary angiography versus no early coronary angiography in this multicenter study. Early angiography was defined as ≤120 minutes from arrival at the percutaneous coronary intervention-capable facility. The primary end point was a composite of efficacy and safety measures, including efficacy measures of survival to discharge, favorable neurologic status at discharge (Cerebral Performance Category score ≤2), echocardiographic measures of left ventricular ejection fraction >50%, and a normal regional wall motion score of 16 within 24 hours of admission. Adverse events included rearrest, pulmonary edema on chest x-ray, acute renal dysfunction, bleeding requiring transfusion or intervention, hypotension (systolic arterial pressure ≤90 mm Hg), and pneumonia. Secondary end points included the incidence of culprit vessels with acute occlusion. RESULTS: The study was terminated prematurely before enrolling the target number of patients. A total of 99 patients were enrolled from 2015 to 2018, including 75 with initially shockable rhythms. Forty-nine patients were randomized to early coronary angiography. The primary end point of efficacy and safety was not different between the 2 groups (55.1% versus 46.0%; P=0.64). Early coronary angiography was not associated with any significant increase in survival (55.1% versus 48.0%; P=0.55) or adverse events (26.5% versus 26.0%; P=1.00). Early coronary angiography revealed a culprit vessel in 47%, with a total of 14% of patients undergoing early coronary angiography having an acutely occluded culprit coronary artery. CONCLUSIONS: This underpowered study, when considered together with previous clinical trials, does not support early coronary angiography for comatose survivors of cardiac arrest without ST elevation. Whether early detection of occluded potential culprit arteries leads to interventions that improve outcomes requires additional study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02387398.

Cardiopulmonary Resuscitation with Extracorporeal Membrane Oxygenation in a Patient with Profound Accidental Hypothermia and Refractory Ventricular Fibrillation.

We describe a patient with severe accidental hypothermia (≤25.4°C) and prolonged refractory ventricular fibrillation, lasting at least 4 hours and 8 minutes, who underwent cardiopulmonary resuscitation with extracorporeal membrane oxygenation and survived without neurologic deficit.

Outcome of conscious survivors of out-of-hospital cardiac arrest.

AIM: Only up to 20% of patients with out-of-hospital cardiac arrest (OHCA) receive immediate and optimal initial cardiac resuscitation and consequently regain consciousness soon after return of spontaneous circulation (ROSC). In the present study, we compared the outcome of conscious survivors of OHCA presenting with ST-elevation myocardial infarction (STEMI) in post-resuscitation electrocardiogram undergoing immediate invasive coronary strategy with randomly selected STEMI patients without preceding OHCA undergoing primary PCI. METHODS: We conducted a single-centre registry-based analysis of all conscious OHCA survivors with STEMI over the last 10 year period. We gathered clinical and angiographic data and compared them with a randomly selected cohort of non-OHCA patients with STEMI within the same period. Patients were matched by sex, age and STEMI location. RESULTS: 86 conscious survivors of OHCA were admitted between 2006 and 2016. OHCA was witnessed in all patients (85% EMS witnessed), and all patients presented with initial shockable rhythm. Clinical and angiographic features were well matched with randomly selected STEMI patients without OHCA presenting to our department within the same study period. Delay from symptoms to EMS arrival but not delay from EMS to PCI was significantly shorter in conscious OHCA survivors (1.2 ± 1.3 h vs 3.1 ± 3.8 h, p < 0.001), yielding decreased total myocardial ischemic time (2.6 ± 1.3 h vs 4.6 ± 4.0 h, p < 0.001). Hospital and 1-year survival with normal neurological condition in conscious survivors of OHCA (cerebral performance category 1) was excellent and numerically even better than survival of STEMI patients without OHCA. CONCLUSION: Conscious survivors of OHCA with STEMI have excellent survival if they undergo immediate invasive coronary strategy. Since there is no obvious post-resuscitation brain injury in this subgroup of OHCA patients, it is probably shorter duration of myocardial ischemia driven by shorter delay from symptoms to EMS arrival that contributes to the good outcome, which is at least similar to STEMI patients without OHCA.

Pregnancy complicated by influenza A ARDS requiring consecutive VV-ECMO treatment with successful vaginal delivery.

A 29-year-old woman presented with influenza A ARDS at 23+0 weeks of gestation. Mechanical ventilation failed and VV-ECMO was started in a non-ECMO hospital. Transportation was performed on ECMO. Within 5 days ECMO weaning was successful. Fetal condition was stable, and decision to continue pregnancy was taken. However, second VV-ECMO was needed due to ventilator-associated pneumonia. At 25+6 weeks, the patient spontaneously delivered a neonate vaginally. Patient's condition improved, and ECMO could be removed 10 days postpartum. 2-year follow-up showed no severe consequences in the mother and the child.

Emergency percutaneous implantation of veno-arterial extracorporeal membrane oxygenation in the catheterisation laboratory.

AIMS: Our aim was to describe our protocol for emergency percutaneous implantation of femoral veno-arterial extracorporeal membrane oxygenation (VA ECMO) in the catheterisation laboratory and to compare its effectiveness and safety with implantation in the intensive care unit and the operating room. METHODS AND RESULTS: Our retrospective observational study enrolled 56 consecutive patients undergoing VA ECMO implantation in the catheterisation laboratory (n=23), the intensive care unit (n=8) and the operating room (n=25). Among patients undergoing catheterisation laboratory implantation, 11 patients had profound cardiogenic shock but preserved arterial pulsations, and 12 patients had refractory cardiac arrest undergoing automated mechanical chest compression. Using our fluoroscopy-guided protocol, arterial and venous cannulas were successfully implanted and the desired ECMO flow obtained in each patient. There was no vessel perforation/dissection. Moderate/severe GUSTO or BARC 3 and 5 bleeding occurred in 13%. Ipsilateral limb ischaemia occurred in one of eight patients (13%) with upfront perfusion sheath implantation, and in two of three patients (75%) in whom this strategy was not used (p=0.15). There was no infection at the site of cannula implantation. Complications related to implantation in the catheterisation laboratory were comparable to surgical implantation in the operating room and percutaneous implantation in the intensive care unit using ultrasound guidance. CONCLUSIONS: Fluoroscopy-guided emergency implantation of femoral VA ECMO by an interventional cardiologist in the catheterisation laboratory is effective and safe for both patients in cardiogenic shock and those in refractory cardiac arrest.

Invasive strategy in patients with resuscitated cardiac arrest and ST elevation myocardial infarction.

Coronary artery disease is the most frequent cause of sudden cardiac death. There is general consensus that immediate coronary angiography with percutaneous coronary intervention (PCI) should be performed in all conscious and unconscious patients with ST-elevation myocardial infarction in post-resuscitation electrocardiogram. In these patients acute coronary thrombotic lesion ("ACS" lesion) suitable for PCI is typically present in more than 90%. PCI in these patients is not only feasible and safe but highly effective and there is evidence of improved survival with good neurological outcome. PCI of the culprit lesion is the primary goal while PCI of stable obstructive lesions may be postponed unless post-resuscitation cardiogenic shock is present.