Cardiac Catheterization Laboratory Management of the Comatose Adult Patient With an Out-of-Hospital Cardiac Arrest: A Scientific Statement From the American Heart Association.

Out-of-hospital cardiac arrest is a leading cause of death, accounting for ≈50% of all cardiovascular deaths. The prognosis of such individuals is poor, with <10% surviving to hospital discharge. Survival with a favorable neurologic outcome is highest among individuals who present with a witnessed shockable rhythm, received bystander cardiopulmonary resuscitation, achieve return of spontaneous circulation within 15 minutes of arrest, and have evidence of ST-segment elevation on initial ECG after return of spontaneous circulation. The cardiac catheterization laboratory plays an important role in the coordinated Chain of Survival for patients with out-of-hospital cardiac arrest. The catheterization laboratory can be used to provide diagnostic, therapeutic, and resuscitative support after sudden cardiac arrest from many different cardiac causes, but it has a unique importance in the treatment of cardiac arrest resulting from underlying coronary artery disease. Over the past few years, numerous trials have clarified the role of the cardiac catheterization laboratory in the management of resuscitated patients or those with ongoing cardiac arrest. This scientific statement provides an update on the contemporary approach to managing resuscitated patients or those with ongoing cardiac arrest.

Machine Learning Identifies Higher Survival Profile In Extracorporeal Cardiopulmonary Resuscitation.

OBJECTIVES: Extracorporeal cardiopulmonary resuscitation (ECPR) has been shown to improve neurologically favorable survival in patients with refractory out-of-hospital cardiac arrest (OHCA) caused by shockable rhythms. Further refinement of patient selection is needed to focus this resource-intensive therapy on those patients likely to benefit. This study sought to create a selection model using machine learning (ML) tools for refractory cardiac arrest patients undergoing ECPR. DESIGN: Retrospective cohort study. SETTING: Cardiac ICU in a Quaternary Care Center. PATIENTS: Adults 18-75 years old with refractory OHCA caused by a shockable rhythm. METHODS: Three hundred seventy-six consecutive patients with refractory OHCA and a shockable presenting rhythm were analyzed, of which 301 underwent ECPR and cannulation for venoarterial extracorporeal membrane oxygenation. Clinical variables that were widely available at the time of cannulation were analyzed and ranked on their ability to predict neurologically favorable survival. INTERVENTIONS: ML was used to train supervised models and predict favorable neurologic outcomes of ECPR. The best-performing models were internally validated using a holdout test set. MEASUREMENTS AND MAIN RESULTS: Neurologically favorable survival occurred in 119 of 301 patients (40%) receiving ECPR. Rhythm at the time of cannulation, intermittent or sustained return of spontaneous circulation, arrest to extracorporeal membrane oxygenation perfusion time, and lactic acid levels were the most predictive of the 11 variables analyzed. All variables were integrated into a training model that yielded an in-sample area under the receiver-operating characteristic curve (AUC) of 0.89 and a misclassification rate of 0.19. Out-of-sample validation of the model yielded an AUC of 0.80 and a misclassification rate of 0.23, demonstrating acceptable prediction ability. CONCLUSIONS: ML can develop a tiered risk model to guide ECPR patient selection with tailored arrest profiles.

Left ventricular hemodynamics with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: There is considerable debate about the hemodynamic effects of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). AIMS: To evaluate the changes in left ventricular (LV) function, volumes, and work in patients treated with VA-ECMO using invasive LV catheterization and three-dimensional echocardiographic volumes. METHODS: Patients on VA-ECMO underwent invasive hemodynamic evaluation due to concerns regarding candidacy for decannulation. Hemodynamic parameters were reported as means±standard deviations or medians (interquartile ranges) after evaluating for normality. Paired comparisons were done to evaluate hemodynamics at the baseline (highest) and lowest tolerated levels of VA-ECMO support. RESULTS: Twenty patients aged 52.3 ± 15.8 years were included. All patients received VA-ECMO for refractory cardiogenic shock (5/20 SCAI stage D, 15/20 SCAI stage E). At 3.0 (2.0, 4.0) days after VA-ECMO cannulation, the baseline LV ejection fraction was 20% (15%, 27%). The baseline and lowest VA-ECMO flows were 4.0 ± 0.6 and 1.5 ± 0.6 L/min, respectively. Compared to the lowest flow, full VA-ECMO support reduced LV end-diastolic volume [109 ± 81 versus 134 ± 93 mL, p = 0.001], LV end-diastolic pressure (14 ± 9 vs. 19 ± 9 mmHg, p < 0.001), LV stroke work (1858 ± 1413 vs. 2550 ± 1486 mL*mmHg, p = 0.002), and LV pressure-volume area (PVA) (4507 ± 1910 vs. 5193 ± 2388, p = 0.03) respectively. Mean arterial pressure was stable at the highest and lowest flows (80 ± 16 vs. 75 ± 14, respectively; p = 0.08) but arterial elastance was higher at the highest VA-ECMO flow (4.9 ± 2.2 vs lowest flow 2.7 ± 1.6; p < 0.001). CONCLUSIONS: High flow VA-ECMO support significantly reduced LV end-diastolic pressure, end-diastolic volume, stroke work, and PVA compared to minimal support. The Ea was higher and MAP was stable or minimally elevated on high flow.

Extracorporeal cardiopulmonary resuscitation versus standard treatment for refractory out-of-hospital cardiac arrest: a Bayesian meta-analysis.

BACKGROUND: The outcomes of several randomized trials on extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out-of-hospital cardiac arrest were examined using frequentist methods, resulting in a dichotomous interpretation of results based on p-values rather than in the probability of clinically relevant treatment effects. To determine such a probability of a clinically relevant ECPR-based treatment effect on neurological outcomes, the authors of these trials performed a Bayesian meta-analysis of the totality of randomized ECPR evidence. METHODS: A systematic search was applied to three electronic databases. Randomized trials that compared ECPR-based treatment with conventional CPR for refractory out-of-hospital cardiac arrest were included. The study was preregistered in INPLASY (INPLASY2023120060). The primary Bayesian hierarchical meta-analysis estimated the difference in 6-month neurologically favorable survival in patients with all rhythms, and a secondary analysis assessed this difference in patients with shockable rhythms (Bayesian hierarchical random-effects model). Primary Bayesian analyses were performed under vague priors. Outcomes were formulated as estimated median relative risks, mean absolute risk differences, and numbers needed to treat with corresponding 95% credible intervals (CrIs). The posterior probabilities of various clinically relevant absolute risk difference thresholds were estimated. RESULTS: Three randomized trials were included in the analysis (ECPR, n = 209 patients; conventional CPR, n = 211 patients). The estimated median relative risk of ECPR for 6-month neurologically favorable survival was 1.47 (95%CrI 0.73-3.32) with a mean absolute risk difference of 8.7% (- 5.0; 42.7%) in patients with all rhythms, and the median relative risk was 1.54 (95%CrI 0.79-3.71) with a mean absolute risk difference of 10.8% (95%CrI - 4.2; 73.9%) in patients with shockable rhythms. The posterior probabilities of an absolute risk difference > 0% and > 5% were 91.0% and 71.1% in patients with all rhythms and 92.4% and 75.8% in patients with shockable rhythms, respectively. CONCLUSION: The current Bayesian meta-analysis found a 71.1% and 75.8% posterior probability of a clinically relevant ECPR-based treatment effect on 6-month neurologically favorable survival in patients with all rhythms and shockable rhythms. These results must be interpreted within the context of the reported credible intervals and varying designs of the randomized trials. REGISTRATION: INPLASY (INPLASY2023120060, December 14th, 2023, https://doi.org/10.37766/inplasy2023.12.0060 ).

Evolution of distal limb perfusion management in adult peripheral venoarterial extracorporeal membrane oxygenation with femoral artery cannulation.

Limb ischaemia is a clinically relevant complication of venoarterial extracorporeal membrane oxygenation (VA ECMO) with femoral artery cannulation. No selective distal perfusion or other advanced techniques were used in the past to maintain adequate distal limb perfusion. A more recent trend is the shift from the reactive or emergency management to the pro-active or prophylactic placement of a distal perfusion cannula to avoid or reduce limb ischaemia-related complications. Multiple alternative cannulation techniques to the distal perfusion cannula have been developed to maintain distal limb perfusion, including end-to-side grafting, external or endovascular femoro-femoral bypass, retrograde limb perfusion (e.g., via the posterior tibial, dorsalis pedis or anterior tibial artery), and, more recently, use of a bidirectional cannula. Venous congestion has also been recognized as a potential contributing factor to limb ischaemia development and specific techniques have been described with facilitated venous drainage or bilateral cannulation being the most recent, to reduce or avoid venous stasis as a contributor to impaired limb perfusion. Advances in monitoring techniques, such as near-infrared spectroscopy and duplex ultrasound analysis, have been applied to improve decision-making regarding both the monitoring and management of limb ischaemia. This narrative review describes the evolution of techniques used for distal limb perfusion during peripheral VA ECMO.

Extracorporeal CPR after the INCEPTION trial: No one steps twice into the same river.

The use of veno-arterial extracorporeal membrane oxygenation as extracorporeal cardiopulmonary resuscitation in patients suffering out-of-hospital cardiac arrest, largely increased in the last decade despite evidence supporting this practice being limited to non-randomized studies. However, between 2020 and 2023, four randomized studies were published comparing extracorporeal cardiopulmonary resuscitation to conventional cardiopulmonary resuscitation with controversial findings that triggered great debates. In this controversy, we discuss merits and pitfalls, and provide a critical interpretation of the available evidence from randomized trials on the use of extracorporeal cardiopulmonary resuscitation, with a particular focus on the recent multi-center INCEPTION trial.

Coronary artery disease burden relation with the presentation of acute cardiac events and ventricular fibrillation.

OBJECTIVES: Evaluate the differences in coronary artery disease (CAD) burden between patients with ischemic resuscitated, ischemic refractory VT/VF OHCA events and N/STEMI. BACKGROUND: Refractory out-of-hospital cardiac arrest patients presenting with initial shockable rhythms (VT/VF OHCA) have the highest mortality among patients with acute cardiac events. No predictors of VT/VF OHCA refractoriness have been identified. METHODS: A retrospective cohort design was used to assess baseline characteristics, clinical outcomes, and the angiographic severity of disease among patients with VT/VF OHCA undergoing emergent coronary angiography at the University of Minnesota Medical Center. The Gensini score was calculated for all patients to assess the angiographic burden of CAD. For patients with ischemia-related cardiac arrest, outcomes were further compared to an independent non-OHCA population presenting with N/STEMI. RESULTS: During the study period, 538 patients were admitted after VT/VF OHCA. Among them, 305 presented with resuscitated, and 233 with refractory VT/VF. 66% of resuscitated and 70% of refractory VT/VF had an underlying, angiographically documented, ischemic etiology. Ischemic resuscitated and refractory VT/VF had significant differences in Gensini score, (80.7 ± 3.6 and 127.6 ± 7.1, respectively, p < 0.001) and survival (77.3% and 30.0%, respectively, p < 0.001). Both groups had a higher CAD burden and worse survival than the non-OHCA N/STEMI population (360 patients). Ischemic refractory VT/VF was significantly more likely to present with chronic total occlusion in comparison to both N/STEMI and ischemic resuscitated VT/VF. CONCLUSION: Ischemia-related, refractory VT/VF OHCA has a higher burden of CAD and the presence of CTOs compared to resuscitated VT/VF OHCA and N/STEMI.

Improved Survival With Extracorporeal Cardiopulmonary Resuscitation Despite Progressive Metabolic Derangement Associated With Prolonged Resuscitation.

BACKGROUND: The likelihood of neurologically favorable survival declines with prolonged resuscitation. However, the ability of extracorporeal cardiopulmonary resuscitation (ECPR) to modulate this decline is unknown. Our aim was to examine the effects of resuscitation duration on survival and metabolic profile in patients who undergo ECPR for refractory ventricular fibrillation/ventricular tachycardia out-of-hospital cardiac arrest. METHODS: We retrospectively evaluated survival in 160 consecutive adults with refractory ventricular fibrillation/ventricular tachycardia out-of-hospital cardiac arrest treated with the University of Minnesota (UMN) ECPR protocol (transport with ongoing cardiopulmonary resuscitation [CPR] to the cardiac catheterization laboratory for ECPR) compared with 654 adults who had received standard CPR in the amiodarone arm of the ALPS trial (Amiodarone, Lidocaine, or Placebo Study). We evaluated the metabolic changes and rate of survival in relation to duration of CPR in UMN-ECPR patients. RESULTS: Neurologically favorable survival was significantly higher in UMN-ECPR patients versus ALPS patients (33% versus 23%; P=0.01) overall. The mean duration of CPR was also significantly longer for UMN-ECPR patients versus ALPS patients (60 minutes versus 35 minutes; P<0.001). Analysis of the effect of CPR duration on neurologically favorable survival demonstrated significantly higher neurologically favorable survival for UMN-ECPR patients compared with ALPS patients at each CPR duration interval <60 minutes; however, longer CPR duration was associated with a progressive decline in neurologically favorable survival in both groups. All UMN-ECPR patients with 20 to 29 minutes of CPR (8 of 8) survived with neurologically favorable status compared with 24% (24 of 102) of ALPS patients with the same duration of CPR. There were no neurologically favorable survivors in the ALPS cohort with CPR ≥40 minutes, whereas neurologically favorable survival was 25% (9 of 36) for UMN-ECPR patients with 50 to 59 minutes of CPR and 19% with ≥60 minutes of CPR. Relative risk of mortality or poor neurological function was significantly reduced in UMN-ECPR patients with CPR duration ≥60 minutes. Significant metabolic changes included decline in pH, increased lactic acid and arterial partial pressure of carbon dioxide, and thickened left ventricular wall with prolonged professional CPR. CONCLUSIONS: ECPR was associated with improved neurologically favorable survival at all CPR durations <60 minutes despite severe progressive metabolic derangement. However, CPR duration remains a critical determinate of survival.

Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial.

BACKGROUND: Among patients with out-of-hospital cardiac arrest (OHCA) and ventricular fibrillation, more than half present with refractory ventricular fibrillation unresponsive to initial standard advanced cardiac life support (ACLS) treatment. We did the first randomised clinical trial in the USA of extracorporeal membrane oxygenation (ECMO)-facilitated resuscitation versus standard ACLS treatment in patients with OHCA and refractory ventricular fibrillation. METHODS: For this phase 2, single centre, open-label, adaptive, safety and efficacy randomised clinical trial, we included adults aged 18-75 years presenting to the University of Minnesota Medical Center (MN, USA) with OHCA and refractory ventricular fibrillation, no return of spontaneous circulation after three shocks, automated cardiopulmonary resuscitation with a Lund University Cardiac Arrest System, and estimated transfer time shorter than 30 min. Patients were randomly assigned to early ECMO-facilitated resuscitation or standard ACLS treatment on hospital arrival by use of a secure schedule generated with permuted blocks of randomly varying block sizes. Allocation concealment was achieved by use of a randomisation schedule that required scratching off an opaque layer to reveal assignment. The primary outcome was survival to hospital discharge. Secondary outcomes were safety, survival, and functional assessment at hospital discharge and at 3 months and 6 months after discharge. All analyses were done on an intention-to-treat basis. The study qualified for exception from informed consent (21 Code of Federal Regulations 50.24). The ARREST trial is registered with ClinicalTrials.gov, NCT03880565. FINDINGS: Between Aug 8, 2019, and June 14, 2020, 36 patients were assessed for inclusion. After exclusion of six patients, 30 were randomly assigned to standard ACLS treatment (n=15) or to early ECMO-facilitated resuscitation (n=15). One patient in the ECMO-facilitated resuscitation group withdrew from the study before discharge. The mean age was 59 years (range 36-73), and 25 (83%) of 30 patients were men. Survival to hospital discharge was observed in one (7%) of 15 patients (95% credible interval 1·6-30·2) in the standard ACLS treatment group versus six (43%) of 14 patients (21·3-67·7) in the early ECMO-facilitated resuscitation group (risk difference 36·2%, 3·7-59·2; posterior probability of ECMO superiority 0·9861). The study was terminated at the first preplanned interim analysis by the National Heart, Lung, and Blood Institute after unanimous recommendation from the Data Safety Monitoring Board after enrolling 30 patients because the posterior probability of ECMO superiority exceeded the prespecified monitoring boundary. Cumulative 6-month survival was significantly better in the early ECMO group than in the standard ACLS group. No unanticipated serious adverse events were observed. INTERPRETATION: Early ECMO-facilitated resuscitation for patients with OHCA and refractory ventricular fibrillation significantly improved survival to hospital discharge compared with standard ACLS treatment. FUNDING: National Heart, Lung, and Blood Institute.

The Evolving Role of the Cardiac Catheterization Laboratory in the Management of Patients With Out-of-Hospital Cardiac Arrest: A Scientific Statement From the American Heart Association.

Coronary artery disease is prevalent in different causes of out-of-hospital cardiac arrest (OHCA), especially in individuals presenting with shockable rhythms of ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT). The purpose of this report is to review the known prevalence and potential importance of coronary artery disease in patients with OHCA and to describe the emerging paradigm of treatment with advanced perfusion/reperfusion techniques and their potential benefits on the basis of available evidence. Although randomized clinical trials are planned or ongoing, current scientific evidence rests principally on observational case series with their potential confounding selection bias. Among patients resuscitated from VF/pVT OHCA with ST-segment elevation on their postresuscitation ECG, the prevalence of coronary artery disease has been shown to be 70% to 85%. More than 90% of these patients have had successful percutaneous coronary intervention. Conversely, among patients resuscitated from VF/pVT OHCA without ST-segment elevation on their postresuscitation ECG, the prevalence of coronary artery disease has been shown to be 25% to 50%. For these patients, early access to the cardiac catheterization laboratory is associated with a 10% to 15% absolute higher functionally favorable survival rate compared with more conservative approaches of late or no access to the cardiac catheterization laboratory. In patients with VF/pVT OHCA refractory to standard treatment, a new treatment paradigm is also emerging that uses venoarterial extracorporeal membrane oxygenation to facilitate return of normal perfusion and to support further resuscitation efforts, including coronary angiography and percutaneous coronary intervention. The burden of coronary artery disease is high in this patient population, presumably causative in most patients. The strategy of venoarterial extracorporeal membrane oxygenation, coronary angiography, and percutaneous coronary intervention has resulted in functionally favorable survival rates ranging from 9% to 45% in observational studies in this patient population. Patients with VF/pVT should be considered at the highest severity in the continuum of acute coronary syndromes. These patients have a significant burden of coronary artery disease and acute coronary thrombotic events. Evidence from randomized trials will further define optimal clinical practice.

Rationale and methods of the Advanced R2Eperfusion STrategies for Refractory Cardiac Arrest (ARREST) trial.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation has emerged as a prominent therapy for patients with refractory cardiac arrest. However, the optimal time of initiation remains unknown. AIM: The aim was to assess the rate of survival to hospital discharge in adult patients with refractory ventricular fibrillation/pulseless ventricular tachycardia out-of-hospital cardiac arrest treated with 1 of 2 local standards of care: (1) early venoarterial extracorporeal membrane oxygenation-facilitated resuscitation for circulatory support and percutaneous coronary intervention, when needed, or (2) standard advanced cardiac life support resuscitation. DESIGN: Phase II, single-center, partially blinded, prospective, intention-to-treat, safety and efficacy clinical trial. POPULATION: Adults (aged 18-75), initial out-of-hospital cardiac arrest rhythm of ventricular fibrillation/pulseless ventricular tachycardia, no ROSC following 3 shocks, body morphology to accommodate a Lund University Cardiac Arrest System automated cardiopulmonary resuscitation device, and transfer time of <30 minutes. SETTING: Hospital-based. OUTCOMES: Primary: survival to hospital discharge. Secondary: safety, survival, and functional assessment at hospital discharge and 3 and 6 months, and cost. SAMPLE SIZE: Assuming success rates of 12% versus 37% in the 2 arms and 90% power, a type 1 error rate of .05, and a 15% rate of withdrawal prior to hospital discharge, the required sample size is N = 174 evaluated patients. CONCLUSIONS: The ARREST trial will generate safety/effectiveness data and comparative costs associated with extracorporeal cardiopulmonary resuscitation, informing broader implementation and a definitive Phase III clinical trial.

ETV2-null porcine embryos survive to post-implantation following incomplete enucleation.

Blind enucleation is used in porcine somatic cell nuclear transfer (SCNT) to remove the metaphase II (MII) spindle from the oocyte. Deviation of the MII spindle location, however, leads to incomplete enucleation (IE). Here, we report that the rate of complete enucleation (CE) using the blind method was 80.2 ± 1.7%, although this significantly increased when the polar body-MII deviation was minimized (≦45°). While it is established that IE embryos will not survive to full term, the effect of IE on early stage development is unknown. We have previously demonstrated in mice and pigs that ETV2 deletion results in embryonic lethality due to the lack of hematoendothelial lineages. We observed that ETV2-null cloned embryos derived from blindly and incompletely enucleated oocytes had both WT and mutant sequences at E18 and, using FISH analysis, we observed triploidy. We also compared SCNT embryos generated from either CE or intentionally IE oocytes using the spindle viewer system. We observed a higher in vitro blastocyst rate in the IE versus the CE-SCNT embryos (31.9 ± 3.2% vs 21.0 ± 2.1%). Based on known processes in normal fertilization, we infer that the IE-SCNT embryos extruded the haploid second PB after fusion with donor fibroblasts and formed a near-triploid aneuploid nucleus in each blastomere. These studies demonstrate the peri-implantation survival of residual haploid nuclei following IE and emphasize the need for complete enucleation especially for the analysis of SCNT embryos in the peri-implantation stage and will, further, impact the field of reverse xenotransplantation.

Refractory cardiac arrest: where extracorporeal cardiopulmonary resuscitation fits.

PURPOSE OF REVIEW: Extracorporeal cardiopulmonary resuscitation (ECPR) is a powerful technique increasingly used to care for patients with refractory cardiac arrest. This review will detail where ECPR fits in the current care of cardiac arrest patients, including the key aspects of ECPR deployment and patient selection shown to maximize its benefit. RECENT FINDINGS: ECPR has been shown to improve neurologically favourable survival in patients with refractory cardiac arrest in numerous nonrandomized cohort studies. The haemodynamic, oxygenation and ventilation support provided by ECPR eliminates the need for return of spontaneous circulation (ROSC) and prevents ongoing injury from shock or rearrest. However, ECPR is one component of an entire system of resuscitation care necessary for positive outcomes. The intense resources needed require that patient eligibility criteria are well delineated to direct ECPR to patients likely to benefit. The other components of the system, including emergency medical services, cannulation teams and postarrest care teams, also require substantial training and dedication. SUMMARY: ECPR is a system of resuscitation care that must be optimized at every level to successfully treat patients with refractory cardiac arrest.

Extracorporeal cardiopulmonary resuscitation for cardiac arrest.

PURPOSE OF REVIEW: Extracorporeal cardiopulmonary resuscitation (ECPR) is a contemporary resuscitation approach that employs veno-arterial extracorporeal membrane oxygenation (VA-ECMO). This approach is increasingly used worldwide to mitigate the widespread hemodynamic and multiorgan dysfunction that accompanies cardiac arrest. RECENT FINDINGS: In this review, the physiology of VA-ECMO and ECPR, the role of ECPR in contemporary resuscitation care, the complications associated with ECPR and VA-ECMO usage, and intensive care considerations for this population are discussed. SUMMARY: ECPR offers a promising mechanism to mitigate multiorgan injury and allow time for the institution of supportive interventions required to effectively treat cardiac arrest. More prospective data in the context of extensive prehospital and hospital collaboration is needed to promote its successful use.

Outcomes of intermediate-risk patients treated with transcatheter and surgical aortic valve replacement in the Veterans Affairs Healthcare System: A single center 20-year experience.

BACKGROUND: Transfemoral transcatheter aortic valve replacement (TAVR) was superior to surgical aortic valve replacement (SAVR) in the placement of aortic transcatheter valves (PARTNER) 2A trial (P2). The generalizability of the trial results to the broader population of patients with intermediate surgical risk remains unknown. OBJECTIVE: To compare the outcomes of SAVR and TAVR among patients with intermediate surgical risk treated in the VA Healthcare System. METHODS: We retrospectively analyzed the clinical characteristics and outcomes on all SAVR (1987-2014) and TAVR procedures (2015-2017) performed at the Minneapolis VA Healthcare System. Patients were divided into three groups based on their estimated 30-day mortality risk. The primary outcome was a composite of death or stroke at 30-days. RESULTS: A total of 1,049 patients underwent SAVR with (n = 468, 45%) or without CABG (n = 581, 55%) and 110 underwent TAVR during the study period. Intermediate-risk patients represented 29.4% and 40% of patients undergoing SAVR and TAVR, respectively. The predicted 30-day mortality risk of intermediate-risk patients was 5.5% for the SAVR group and 5.2% for the TAVR group (P = 0.54). The observed combined rate of stroke or death at 30-days for intermediate-risk patients treated with SAVR and TAVR was 11% and 2.2%, respectively (P = 0.05). The results for SAVR and TAVR at the VA were comparable to the P2 trial and STS database (all P = NS). The results did not change when the analysis was restricted to a more contemporary (2005-2014) surgical cohort or isolated SAVR. The number needed to treat to prevent one death/stroke with TAVR was 10. CONCLUSIONS: Adoption of TAVR as the preferred treatment modality in intermediate-risk patients may result in significant improvements in morbidity and mortality.

Synchronized Pulsatile Flow With Low Systolic Output From Veno-Arterial Extracorporeal Membrane Oxygenation Improves Myocardial Recovery After Experimental Cardiac Arrest in Pigs.

Circulatory failure following cardiac arrest (CA) requires catecholamine support and occasionally veno-arterial extracorporeal membrane oxygenation (vaECMO). VaECMO-generated blood flow is continuous and retrograde, increasing ventricular stroke work. Our aim was to assess the benefit of a device generating a pulsatile vaECMO flow synchronized with the heart rhythm lowering systolic vaECMO output on the left ventricular ejection fraction (LVEF) and pulmonary capillary pressure (Pcap) after CA. This experimental randomized study in pigs compared standard nonpulsatile vaECMO (control) with pulsatile synchronized vaECMO (study) group using a pulsatility-generating device. After sedation and intubation, ventricular fibrillation was induced by pacing. After 10-min ventricular fibrillation, cardiopulmonary resuscitation was performed for 20 min then vaECMO, defibrillation and 0.15 µg/kg/min intravenous epinephrine infusion were initiated. Hemodynamics, Pcap, LVEF by echocardiography and angiography were measured at baseline and every 30 min after the vaECMO start until vaECMO and epinephrine were stopped (at 120 min), and 30 min later. Baseline hemodynamics did not differ between groups; 120 min after vaECMO initiation, LVEF by echocardiography and angiography was significantly higher in the study than control group 55 ± 19% versus 34 ± 13% (P = 0.042), 50 ± 16% versus 33 ± 12% (P = 0.043), respectively. Pcap decreased from baseline by 4.2 ± 8.6 mm Hg in the study group but increased by 5.6 ± 5.9 mm Hg in the control group (P = 0.043). Thirty minutes later, LVEF remained higher in the study group 44 ± 7% versus 26 ± 11% (P = 0.008) while Pcap did not differ. A synchronized pulsatile device decreasing systolic output from vaECMO improved LVEF and Pcap in a pig model of CA and resuscitation.

Coronary artery spatial distribution of chronic total occlusions: Insights from a large US registry.

OBJECTIVE: To assess the spatial distribution of chronic total occlusions (CTOs) within the coronary arteries and describe procedural strategies and outcomes during CTO percutaneous coronary intervention (PCI). BACKGROUND: Acute occlusions due to plaque rupture tend to cluster within the proximal third of the coronary artery. METHODS: We examined the clinical and procedural characteristics of 1,348 patients according to lesion location within the coronary tree. RESULTS: A total of 1,369 lesions in 1,348 patients (mean age 66 ± 10 years, 85% male) were included. CTO PCI of proximal segments (n = 633, 46%) was more common than of mid (n = 557, 41%) and distal segments (n = 179, 13%). Patients undergoing CTO PCI of proximal segments were more likely to be smokers (P < 0.01), have prior coronary artery bypass graft surgery (P = 0.03) and lower ejection fraction (P = 0.04). CTOs occurring in proximal segments had longer length (P <0.01), proximal cap ambiguity (P < 0.01), and moderate/severe calcification (P < 0.01) compared to mid or distally located CTOs. Interventional collaterals were more often present in CTO PCI of proximal segments (64%, 53%, 56%, P < 0.01) consistent with the higher use of retrograde approach (47%, 33%, 37%, P < 0.01) relative to antegrade wire escalation (67%, 82%, 82%, P < 0.01). Procedural complexity was higher in CTO PCI of proximal segments (vs. mid and distal): contrast volume= 275 ml (200-375), 260 ml (200-350), 250 ml (175-350), P = 0.01; fluoroscopy time 53 minutes (32-83), 39 minutes (24-65), 40 minutes (22-72), P < 0.01. However, procedural success (87%, 90%, 85%, P = 0.1), technical success (89%, 91%, 88%, P = 0.24), and complications rates (2.8%, 2.5%, 2.2%, P = 0.88) were not different. CONCLUSIONS: The most common target vessel location for CTO PCI is the proximal coronary segment. PCI of proximal occlusions is associated with adverse clinical and angiographic characteristics and often requires use of the retrograde approach, but can be accomplished with high procedural and technical success and low complication rates. © 2016 Wiley Periodicals, Inc.

PEO-PPO Diblock Copolymers Protect Myoblasts from Hypo-Osmotic Stress In Vitro Dependent on Copolymer Size, Composition, and Architecture.

Poloxamer 188, a triblock copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), protects cellular membranes from various stresses. Though numerous block copolymer variants exist, evaluation of alternative architecture, composition, and size has been minimal. Herein, cultured murine myoblasts are exposed to the stresses of hypotonic shock and isotonic recovery, and membrane integrity was evaluated by quantifying release of lactate dehydrogenase. Comparative evaluation of a systematic set of PEO-PPO diblock and PEO-PPO-PEO triblock copolymers demonstrates that the diblock architecture can be protective in vitro. Short PPO blocks hinder protection with >9 PPO units needed for protection at 150 µM and >16 units needed at 14 µM. Addition of a tert-butyl end group enhances protection at reduced concentration. When the end group and PPO length are fixed, increasing the PEO length improves protection. This systematic evaluation establishes a new in vitro screening tool for evaluating membrane-sealing amphiphiles and provides mechanistic insight to guide future copolymer design for membrane stabilization in vivo.

The future is now: neuroprotection during cardiopulmonary resuscitation.

PURPOSE OF REVIEW: Survival with favorable neurological function after cardiac arrest remains low. The purpose of this review is to identify recent advances that focus on neuroprotection during cardiopulmonary resuscitation (CPR). RECENT FINDINGS: Multiple strategies have been shown to enhance neuroprotection during CPR. Brain perfusion during CPR is increased with therapies such as active compression decompression CPR and intrathoracic pressure regulation that improve cardiac preload and decrease intracranial pressure. Head Up CPR has been shown to decrease intracranial pressure thereby increasing cerebral perfusion pressure and cerebral blood flow. Sodium nitroprusside enhanced CPR increases cerebral perfusion, facilitates heat exchange, and improves neurologic survival in swine after cardiac arrest. Postconditioning has been administered during CPR in laboratory settings. Poloxamer 188, a membrane stabilizer, and ischemic postconditioning have been shown to improve cardiac and neural function after cardiac arrest in animal models. Postconditioning with inhaled gases protects the myocardium, with more evidence mounting for the potential for neural protection. SUMMARY: Multiple promising neuroprotective therapies are being developed in animal models of cardiac arrest, and are in early stages of human trials. These therapies have the potential to be bundled together to improve rates of favorable neurological survival after cardiac arrest.