Purpose of reviewThis article offers an overview of recent randomized controlled trials (RCTs) testing the efficacy of veno-arterial extracorporeal membrane oxygenation (VA ECMO) and microaxial flow pump (mAFP) in treating cardiogenic shock, including findings from the DanGer shock trial. It summarizes the clinical implications and limitations of these studies and key decision-making considerations for cardiogenic shock device use.Recent findingsDespite important limitations in all published RCTs, the routine use of VA ECMO for acute myocardial infarction related cardiogenic shock did not demonstrate benefit and should be reserved for selected patients with extreme forms of cardiogenic shock. Conversely, mAFP (Impella CP) appears promising for cardiogenic shock due to ST elevation myocardial infarction. A stepwise approach - initial mAFP use for cardiogenic shock with left ventricular failure, supplemented by VA ECMO if mAFP is inadequate or if severe right ventricular failure is present - may be preferable, but requires validation through RCTs. High complication rates in device arms underscore the need for careful patient selection, preventive strategies, education for centers and operators, and further research.SummaryRecent trials offer insights into mechanical circulatory support in cardiogenic shock, but their real-world applicability is limited. Despite potential benefits, the use of VA ECMO and mAFP is associated with significant complication rates, emphasizing the need for personalized use.

BACKGROUND:It is unclear how invasive resuscitative protocols may impact the time-dependent prognosis of out-of-hospital cardiac arrest (OHCA) resuscitations, or the relationship between intra-arrest transport and outcomes. METHODS:We performed a secondary analysis of the Prague OHCA Study, which randomized refractory OHCAs to "invasive" (intra-arrest transport for possible ECPR initiation) vs. "standard" resuscitation strategies (predominantly performed on-scene). Between groups, we compared outcomes of the initial resuscitation and 180- and 30-day favourable neurological outcomes (CPC 1-2), and within categories based on resuscitation duration (collapse-to-ROSC/ECPR interval). We plotted the dynamic probability of favourable outcomes with increasing durations of unsuccessful resuscitation. RESULTS:Among invasive and standard groups, respectively: 34/124 (27%) vs. 58/132 (44%) had sustained ROSC (difference -17%, 95%CI -5.0, -28); 38/124 (31%) vs. 24/132 (18%) had 30-day favourable neurological outcomes (difference 12%; 95%CI 2.0, 23); and 39/124 (31%) vs. 29/132 (22%) had 180-day favourable neurological outcomes (difference 9.5%; 95%CI -1.3, 20). For favourable outcome cases: standard group resuscitation durations were right-skewed within the first 60 min; for the invasive group the distribution was bimodal, extending to 77 min. For invasive- and standard-treated cases, the probability of favourable outcomes among those in refractory arrest at 30 min was 28% and 7.6%, respectively; declining to 0% at 77 and 60 min. CONCLUSION:In comparison to standard resuscitation, invasive strategy cases had fewer achieve sustained ROSC, however improved overall 30-day favourable neurological outcomes. While standard resuscitation yield was limited to < 60 min, invasive protocols offer a second extended window of potential successful resuscitation.

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. 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 https://doi.org/10.37766/inplasy2023.12.0060 ).

BACKGROUND:Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support. METHODS:These guidelines are based on clinical practice consensus recommendations and scientific statements. We convened an international multidisciplinary consensus panel including 30 clinician-scientists with expertise in ECMO from all chapters of the Extracorporeal Life Support Organization (ELSO). We used a modified Delphi process with three rounds of voting and asked panelists to assess the recommendation levels. RESULTS:We identified five key clinical areas needing guidance: (1) neurological monitoring, (2) post-cannulation early physiological targets and ABI, (3) neurological therapy including medical and surgical intervention, (4) neurological prognostication, and (5) neurological follow-up and outcomes. The consensus produced 30 statements and recommendations regarding key clinical areas. We identified several knowledge gaps to shape future research efforts. CONCLUSIONS:The impact of ABI on morbidity and mortality in ECMO patients is significant. Particularly, early detection and timely intervention are crucial for improving outcomes. These consensus recommendations and scientific statements serve to guide the neurological monitoring and prevention of ABI, and management strategy of ECMO-associated ABI.

Abstract Background The prognosis of refractory out-of-hospital cardiac arrest (OHCA) is generally poor. A recent Prague OHCA study has demonstrated that an invasive approach (including extracorporeal cardiopulmonary resuscitation, ECPR) is a feasible treatment strategy in refractory OHCA. Post-hoc analysis of Prague OHCA showed that patients with initial ventricular fibrillation (VF) had manifested better clinical outcomes than those with non-shockable rhythms irrespective of cardiopulmonary resuscitation (CPR) strategy. However, initial shockable rhythm could deteriorate to a non-shockable rhythm during CPR, mainly after defibrillation. The study aimed to stratify the prognosis of patients according to rhythm profile after initial VF in refractory OHCA during pre-hospital and early hospital periods. Methods The analysis enrolled patients with a witnessed OHCA of presumed cardiac cause, with initial VF, and without early recovery of spontaneous circulation. The primary outcome was a composite of survival with Cerebral Performance in Category (CPC) 1 or 2 at 180 days. Results 155 (median age 56y, 10 % females) patients with initial VF were enrolled. The median (IQR) duration of resuscitation was 54 (33-69) minutes. Overall survival with CPC 1 or 2 was 40.4 %. 71 patients were randomized to invasive CPR arm and 84 subjects were treated with conventional CPR. Out of all invasively treated patients, ECPR (veno-arterial extracorporeal membrane oxygenation, VA ECMO) was used in 56 cases without stable recovery of spontaneous circulation and 8 patients primary allocated in conventional group. A proportion of survival with CPC 1 or 2 varied by rhythm course: ongoing VF (9 / 28; 32 %), recovery of organized rhythm (43 / 63; 68 %), documentation of pulseless electrical activity (7 / 30; 23%), and progression to asystole (4 / 34; 12 %); P < 0.05. Tables 1 and 2 show differences in primary endpoint according to rhythm profile between invasive and conventional study arms. Conclusion Deterioration of initial shockable rhythm to asystole bears a poor prognosis in refractory OHCA even when ECPR is readily available. An invasive approach (including VA ECMO) seems to be beneficial in patients with ongoing VF and with regular electrical activity regardless of effective pulsation.

Background: : We aimed to estimate the effect of extracorporeal cardiopulmonary resuscitation (ECPR) on neurological outcome and mortality, when compared to conventional cardiopulmonary resuscitation (CCPR), using an individual patient data meta-analysis (IPDMA). Methods: : A systematic literature search was performed up to the 20th of October 2022 in the PubMed, EMBASE and CENTRAL databases. For observational studies with unmatched populations, a propensity score including age, location of arrest and initial rhythm was used to match ECPR and CCPR patients in a 1:1 ratio. The primary and secondary outcomes were unfavorable neurological outcome (Cerebral Performance Category of 3-5) and mortality, respectively, which were both collected at different time-points. Results: : Data from 17 studies, including 2064 matched cardiac arrest (CA) patients (1031 ECPR and 1033 CCPR cases) were included. In comparison to CCPR, ECPR was associated with a decreased odds of unfavorable neurological outcome (847, 82.2% vs. 897, 86.8%- OR 0.68 [95%CI 0.53-0.87]; p = 0.002) and death (803, 77.9% vs. 860,83.3%- OR 0.68 [95%CI 0.54-0.86]; p = 0.001). These results were consistent across most of the prespecified subgroups. Moreover, the odds of both unfavorable neurological outcome and mortality were significantly influenced by initial rhythm, cause of arrest and combinations of lactate levels on admission and duration of resuscitation. Conclusions: : This IPDMA showed that ECPR was associated with significantly lower rates of unfavorable neurological outcome and mortality in refractory CA. The overall effect could be influenced by CA characteristics and the severity of the initial injury.

BACKGROUND:The initial rhythm is a known predictor of survival in extracorporeal cardiopulmonary resuscitation (ECPR) patients. However, the effect of the rhythm at hospital admission on outcomes in these patients is less clear. METHODS:This observational, single-center study assessed the influence of the rhythm at hospital admission on 30-day survival and neurological outcomes at discharge in patients who underwent ECPR for out-of-hospital cardiac arrest (OHCA). RESULTS:Between January 2012 and December 2023, 1,219 OHCA patients were admitted, and 210 received ECPR. Of these, 196 patients were analyzed. The average age was 52.9 years (±13), with 80.6 % male. The median time to ECPR initiation was 61 min (IQR 54-72). Patients with ventricular fibrillation as both the initial and admission rhythm had the highest 30-day survival rate (52 %: 35/67), while those with asystole in both instances had the lowest (6 %: 1/17, log-rank p < 0.00001). After adjusting for age, sex, initial rhythm, resuscitation time, location, bystander, and witnessed status, asystole at admission was linked to higher 30-day mortality (OR 4.03, 95 % CI 1.49-12.38, p = 0.009) and worse neurological outcomes (Cerebral Performance Category 3-5) at discharge (OR 4.61, 95 % CI 1.49-17.62, p = 0.013). CONCLUSIONS:The rhythm at hospital admission affects ECPR outcomes. Patients presenting with and maintaining ventricular fibrillation have a higher chance of favorable neurological survival, whereas those presenting with or converting to asystole have poor outcomes. The rhythm at hospital admission appears to be a valuable criterion for deciding on ECPR initiation.

Abstract Background and purpose Both low and higher glucose levels and their tight control were associated with worse prognosis of critically ill patients. We performed a post-hoc analysis of treated Prague OHCA trial population of patients subjected to extracorporeal cardiopulmonary resuscitation (ECPR) vs. standard approach for refractory cardiac arrest, aimed to assess relationship of glucose levels in the first 72 hours after admission to the neurological outcome. Methods Prague OHCA trial enrolled adults with a witnessed refractory OHCA of presumed cardiac origin. In this post-hoc analysis, the effects blood glucose on the best cerebral performance category (CPC) within 180 days was examined. Blood samples for glycemia evaluation were drawn at admission and then every 3 hours within the first 3 days. Fischer exact test was used to analyze the impact on the prognosis (CPC 1-2 = good and CPC 3-5 = poor prognosis). Results Patients with CPC 1-2 did not differ in blood glucose on admission from patients with CPC 3-5. However, patients with type 2 diabetes mellitus had significantly worse prognosis (83 vs. 60% of diabetics vs. non-diabetics had poor prognosis, p = 0.007). Glycemia on admission was slightly but significantly related to the amount of given epinephrine and to the serum triglycerides. Patients having at least 3 glucose levels >10 mmol/L within the first 72 hours had worse neurological prognosis: CPC 1-2 was reached in 61.4% of patients with less than 3 levels >10 mmol/L, but only in 24% of patients that fulfilled this criterion (p=0.000004). Conclusions Repeatedly higher blood glucose within the first 72 hours after admission for prolonged cardiac arrest are related to worse prognosis.

Randomized data evaluating the impact of the extracorporeal cardiopulmonary resuscitation (ECPR) approach on long-term clinical outcomes in patients with refractory out-of-hospital cardiac arrest (OHCA) are lacking. The objective of this follow-up study was to assess the long-term clinical outcomes of the ECPR-based versus CCPR approach. The Prague OHCA trial was a single-center, randomized, open-label trial. Patients with witnessed refractory OHCA of presumed cardiac origin, without return of spontaneous circulation, were randomized during ongoing resuscitation on scene to conventional CPR (CCPR) or an ECPR-based approach (intra-arrest transport, ECPR if ROSC is not achieved prehospital and immediate invasive assessment). From March 2013 to October 2020, 264 patients were randomized during ongoing resuscitation on scene, and 256 patients were enrolled. Long-term follow-up was performed 5.3 (interquartile range 3.8–7.2) years after initial randomization and was completed in 255 of 256 patients (99.6

Acute myocarditis affects around 4–14 people per 100 000 each year globally. Approximately 2% to 9% of patients have haemodynamic instability and require inotropic agents or mechanical circulatory support (MCS) devices to facilitate functional recovery. These patients have an approximately 28% rate of mortality or heart transplant at 60 days.1 This case study underscores the key decision points, considerations, and advantages of combining both Impella and veno-arterial extracorporeal membrane oxygenation (VA ECMO) in the treatment of patients suffering from advanced stages of cardiogenic shock (CS) due to fulminant myocarditis. A 22-year-old male was admitted to the intensive care unit due to sustained ventricular tachycardia (VT). He experienced fatigue for the past 3 days, and on the night of admission, he reported palpitations and dyspnoea. The patient had a fever on the first day of hospitalization, which he suffered from for 3 days, with a high of 39.1°C. He also vomited for the first two nights. The initial ECG obtained from the ambulance revealed sustained VT (Figure 1A). Upon admission, the subsequent ECG displayed sinus rhythm, into which he spontaneously converted during transport; pathological ST elevations were seen in leads I, aVL, and V1–V5, and deep Q waves were noted in leads V1-V3 (Figure 1B). Despite these manifestations, vital signs upon admission were a blood pressure of 93/53 mmHg, a pulse rate of 101 beats per minute, and a lactate level of 1.9 mmol/L. He was free of symptoms during the initial assessment. The patient was diagnosed with Addison's disease, autoimmune hypothyroidism, and heart failure with a mildly reduced left ventricle ejection fraction (LVEF) of 45% in 2020. The treatment included prednisone, levothyroxine, ramipril, and bisoprolol. Cardiac magnetic resonance (CMR) 3 months after the treatment initiation showed normal left ventricular (LV) function without the presence of late gadolinium enhancement (LGE), and the temporary LV dysfunction was attributed to an endocrine disorder. Ramipril and bisoprolol were discontinued after the improvement of LVEF, and the patient continued to use levothyroxine and prednisone. Since then, the heart function has been assessed as normal with the use of echocardiography during regular check-ups with his cardiologist. The echocardiography performed on admission revealed significant reduction of LVEF (28%) due to severe global hypokinesis (Video S1). The right ventricle (RV) was of normal size with decreased systolic function [tricuspid annular plane systolic excursion (TAPSE) 14 mm and 9 cm s′ tissue Doppler imaging (TDI) of tricuspid annulus]. The initial value of highly sensitive troponin I was 18 752 ng/L with a peak value of 27 157 ng/L on the next day. The NT-proBNP level was 10 125 ng/L, and the peak lactate was 3.9 mmol/L. Selective coronary angiography was normal (Video S2A and Video S2B). On the second day, the patient developed signs of low cardiac output syndrome. Urgent CMR was performed, which revealed several non-contiguous midmyocardial LGE within the interventricular septum and LV free walls suggesting non-ischaemic damage of the LV myocardium (Video S3, Figure 2A). All laboratory tests on possible viral agents (including hepatitis and HIV) came back negative. For the suspected Addisonian crisis, we administered corticosteroids from the first day, starting with a bolus of 100 mg of hydrocortisone followed by 200 mg administered daily in four doses.2 On the second morning, the patient received inotropic support due to low cardiac output syndrome (ScV02 36.9%, VTI [velocity time integral] LVOT 8 cm) using levosimendan. In the evening, the patient experienced recurrent episodes of sustained VT with four defibrillations; intravenous amiodarone was administered to prevent VT recurrence. After this episode, his echocardiography showed progressively worsening LV dysfunction with an LVEF of 10%, and the patient experienced severe pulmonary oedema, which required treatment with non-invasive ventilation support (FiO2 100%). A rapid shock-team call was made, and the decision was to initiate Impella CP Smart support, inserted through the right femoral artery with an initial flow of 3.2 L/min (P8), which led to rapid regression of pulmonary oedema, lactate normalization, and restoration of urine output. Since the Impella implantation, the patient has been free from any arrhythmias. However, on the morning of the next day, the persistence of severely reduced LV systolic function, together with worsened RV function (TAPSE 12 mm) and high haemolysis (serum free haemoglobin 3058.5 mg/L) on Impella support, led to the decision to start awake veno-arterial extracorporeal membrane oxygenation (Maquet Cardiohelp, 19F arterial cannula, 23F vein cannula) with a flow of 4.2 L/min. The Impella flow was then lowered to 1.2 L (P2) as an active LV unloading strategy. This approach resolved the problem of haemolysis (the serum free haemoglobin was 79.8 mg/L the next day). Immediately after the ECMO implantation, an EMB was performed with preliminary results suggestive of acute necrotizing lymphocytic myocarditis (Figure 3). Based on the EMB results, treatment with high pulses of corticosteroids was started on the same day (a pulse of 1 g of methylprednisolone on the first day, followed by a dose of 100 mg of methylprednisolone on the second day, then reducing the dose to 80 mg a day for the next 7 days) along with high-dose intravenous immunoglobulins (1 mg/kg in total, divided into 3 doses given over 3 days). After starting with higher doses of corticosteroids for 7 days, the patient was switched to hydrocortisone at 200 mg per day due to ongoing stressful circumstances requiring substitution. After another 7 days, the dosage was reduced to prednisone at 20 mg per day. Fludrocortisone at a dosage of 0.1 mg per day was added later, and the dosage was gradually reduced over the following months with the endocrinologist's guidance. The patient was on ECMO and Impella for 5 days with minimal LV pulsatility (Figure 4). On day 6, he began to show the primary signs of significant RV recovery, and over the next few days, we observed further gradual improvement in both LV and RV function. This enabled us to slowly wean off ECMO, with successful fully percutaneous explantation of both the Impella and ECMO on the 8th and 9th days post-implantation, respectively (Figure 5).Details of the laboratory results are presented in Figure 6. This case study has several important implications. First, it describes the key steps of the diagnostic and decision-making process in fulminant myocarditis. Second, it underscores the advantages of combining both Impella and ECMO, often referred to as ECPELLA or ECMELLA, in the treatment of patients suffering from advanced stages of CS due to fulminant myocarditis. Given the limited availability of data concerning the management of fulminant myocarditis with CS, we posit that this case report has the potential to illuminate the importance of early initiation of left ventricular (LV) unloading and combined support in cases with deteriorating CS. Both the European Society of Cardiology (ESC)3 and the American Heart Association (AHA)4 currently advise the use of MCS in cases of acute myocarditis complicated by refractory heart failure or CS.5 Fulminant myocarditis often proves to be reversible, making the temporary utilization of short-term MCS devices an appealing therapeutic strategy. An analysis of myocarditis management trends in the United States from 2005 to 2014 revealed an increasing rate of temporary MCS utilization, growing from 4.5% to 8.6%.6 V-A ECMO remains the most widely employed MCS in fulminant myocarditis complicated by refractory CS.7 V-A ECMO provides robust circulatory support at the expense of elevated LV afterload and considerable risks of bleeding, vascular, and ischaemic complications. That's why we opted for the Impella CP Smart device implantation due to its advantages over ECMO and other MCS. Notably, Impella actively unloads the LV, favouring myocardial recovery and improvement in pulmonary oedema compared with VA-ECMO. Direct LV unloading, reduced mechanical workload, lowered myocardial oxygen demand, decreased wall stress, and improved subendocardial coronary blood flow may explain the immediate effect of device insertion on the disappearance of VT in our patient. However, all MCS devices have inherent limitations and potential complications. Impella CP provides limited LV support, and high pump flows may lead to significant haemolysis. Given the high haemolysis, worsened RV function, and expected recovery timeline spanning days to weeks, we selected peripheral percutaneous V-A ECMO. This choice enabled us to decrease Impella flow and ensure complete biventricular circulatory and respiratory support until the appearance of cardiac recovery. There are also other possible MCS combinations; one of the most deployed is the use of an intra-aortic balloon pump (IABP) with VA ECMO. However, the IABP provides only passive and limited LV support, which may not be sufficient in severe CS cases. Additionally, a recently published retrospective registry study from Japan revealed that a substantial proportion of patients with myocarditis complicated by CS can be managed by Impella alone without VA ECMO, and the survival rate for the Impella standalone group in this study was high (83.2%).8 Despite the lack of prospective and randomized data, there are experimental and clinical studies showing better efficacy of ECPELLA compared with the IABP combination with VA ECMO, although at the expense of higher complication rates with Impella compared with IABP.9 The survival advantage of ECPELLA over those solely treated with VA ECMO has been highlighted in various observational studies.10 However, contrasting these encouraging findings, a case series from a high-volume centre in Hannover, Germany, involving seven patients with influenza-associated myocarditis supported by ECPELLA, indicated a zero survival rate.11 Considering the variability in myocarditis presentation and severity, gathering robust evidence remains challenging. To achieve optimal outcomes, we recommend a comprehensive case assessment, shock-team deliberation, and decision-making involving strategies for haemodynamic deterioration. Tailoring the indication and timing of MCS devices to individual patients is essential, dependent on numerous factors outlined in Figure 7. Emphasis should be placed on LV unloading, rapid diagnosis, and treatment. Furthermore, it is important to note that the combination of ECMO and Impella is associated with elevated complication rates, primarily bleeding and vascular complications.12 To mitigate these issues, comprehensive strategies, including ultrasound and X-ray guided procedures and MCS insertions, fully percutaneous closure techniques, and intensive monitoring of bleeding, coagulation, and haemolysis, should be employed. Additionally, the patient was kept awake throughout the course of hospitalization, and the respiratory failure in this case was effectively managed by non-invasive ventilation and early Impella CP. The awake MCS strategy is used for most CS patients in our hospital. In a retrospective observational study from Paris, the awake ECMO group had significantly lower rates of pneumonia, tracheostomy, renal replacement therapy, less antibiotic and sedative consumption, and even reduced short-term and long-term mortality compared with ventilated patients.13 This study confirms previous reports suggesting that an awake approach to patients treated with MCS is feasible and effective for a significant proportion of patients with CS. The patient was discharged with an LVEF of 58%. After an 8-week follow-up, the patient was free of symptoms, and his LV function was 57% (Video S4). The CMR performed 8 weeks after discharge from the hospital showed no signs of LGE (Figure 2B). At the 6-month follow-up, the patient was still free of symptoms with normal LVEF. In conclusion, the combined use of Impella and ECMO holds potential for reversing the lethal course of refractory CS due to fulminant myocarditis. Success hinges on appropriate patient selection, timing of implantation, active LV unloading, and mitigation of potential complications associated with MCS. In this case, early Impella and VA ECMO implantation proved pivotal in reversing cardiogenic shock and facilitating successful bridge-to-cardiac recovery. Decisions regarding device selection and timing should be tailored to individual patients and coordinated within an experienced shock team. This study was supported by MH CZ-DRO-VFN64165 VFN: General University Hospital in Prague and the Charles University Research Program Cooperation – Intensive Care Medicine. Daniel Rob received consulting honoraria from Abiomed. Jan Belohlavek received consulting honoraria from Abiomed, Getinge, Resuscitec and Xenios. Michaela Zemkova, Milan Dusik, Jan Pudil, Tomas Palecek and Ivana Vitkova declare that they have no conflict of interest. Video S1. The initial echocardiography – apical four chamber projection. The initial echocardiography revealed significant reduction of ejection fraction (28%) of left ventricle with severe global hypokinesis with slightly better kinesis of the basal parts of left ventricle. Video S2A. Selective coronary angiography. Selective coronary angiography showed coronary arteries without any stenosis. A) right coronary artery. Video S2B. Left coronary artery, left anterior descending artery and left circumflex artery. Video S3. CMR. This video from cardiac magnetic resonance shows reduced ejection fraction of the left ventricle (around 30%), akinesis of the apex and apical halves of anterior and lateral wall of LV and anterior part of interventricular septum. Video S4. Transthoracic echocardiography during follow-up after eight weeks – apical four chamber projection. The echocardiography shows no kinetics disorders of the LV, and its ejection fraction is 57% according to Simpson. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Impressively increasing availability of mechanical circulatory/cardiac support systems (MCSs) worldwide, together with the deepening of the knowledge of critical care medical practitioners, has inevitably led to the discussion about further improvements of intensive care associated to MCS. An appealing topic of the left ventricle (LV) overload related to VA ECMO support endangering myocardial recovery is being widely discussed within the scientific community. Unloading of LV leads to the reduction in LV end-diastolic pressure, reduction in pressure in the left atrium, and decrease in the LV thrombus formation risk. Consequently, better conditions for myocardial recovery, with comfortable filling pressures and a better oxygen delivery/demand ratio, are achieved. The combination of VA ECMO and Impella device, also called ECPELLA, seems to be a promising strategy that may bring the improvement of CS mortality rates. The series of presented trials and meta-analyses clearly showed the potential benefits of this strategy. However, the ongoing research has brought a series of new questions, such as whether Impella itself is the only appropriate unloading modality, or any other approach to unload LV would be beneficial in the same way. Benefits and potential risks of LV unloading and its timing are being discussed in this current review.

Abstract Aims Fabry disease (FD) is a multisystemic lysosomal storage disorder caused by a defect in the alpha-galactosidase A gene that manifests as a phenocopy of hypertrophic cardiomyopathy. We assessed the echocardiographic 3D left ventricular (LV) strain of patients with FD in relation to heart failure severity using natriuretic peptides, the presence of a cardiovascular magnetic resonance (CMR) late gadolinium enhancement scar, and long-term prognosis. Methods and results 3D echocardiography was feasible in 75/99 patients with FD [aged 47 ± 14 years, 44% males, LV ejection fraction (EF) 65 ± 6% and 51% with hypertrophy or concentric remodelling of the LV]. Long-term prognosis (death, heart failure decompensation, or cardiovascular hospitalization) was assessed over a median follow-up of 3.1 years. A stronger correlation was observed for N-terminal pro-brain natriuretic peptide levels with 3D LV global longitudinal strain (GLS, r = −0.49, P < 0.0001) than with 3D LV global circumferential strain (GCS, r = −0.38, P < 0.001) or 3D LVEF (r = −0.25, P = 0.036). Individuals with posterolateral scar on CMR had lower posterolateral 3D circumferential strain (CS; P = 0.009). 3D LV-GLS was associated with long-term prognosis [adjusted hazard ratio 0.85 (confidence interval 0.75–0.95), P = 0.004], while 3D LV-GCS and 3D LVEF were not (P = 0.284 and P = 0.324). Conclusion 3D LV-GLS is associated with both heart failure severity measured by natriuretic peptide levels and long-term prognosis. Decreased posterolateral 3D CS reflects typical posterolateral scarring in FD. Where feasible, 3D-strain echocardiography can be used for a comprehensive mechanical assessment of the LV in patients with FD.

Background Refractory out-of-hospital cardiac arrest (OHCA) treated with standard advanced cardiac life support (ACLS) has poor outcomes. Transport to hospital followed by in-hospital extracorporeal cardiopulmonary resuscitation (ECPR) initiation may improve outcomes. We performed a pooled individual patient data analysis of two randomised controlled trials evaluating ECPR based approach in OHCA.Methods The individual patient data from two published randomised controlled trials (RCTs) were pooled: ARREST (enrolled Aug 2019-June 2020; NCT03880565) and PRAGUE-OHCA (enrolled March 1, 2013-Oct 25, 2020; NCT01511666). Both trials enrolled patients with refractory OHCA and compared: intra-arrest transport with in -hospital ECPR initiation (invasive approach) versus continued standard ACLS. The primary outcome was 180-day survival with favourable neurological outcome (defined as Cerebral Performance Category 1-2). Secondary outcomes included: cumulative survival at 180 days, 30-day favourable neurological survival, and 30-day cardiac recovery. Risk of bias in each trial was assessed by two independent reviewers using the Cochrane risk-of-bias tool. Heterogeneity was assessed via Forest plots.Findings The two RCTs included 286 patients. Of those randomised to the invasive (n = 147) and standard (n = 139) groups, respectively: the median age was 57 (IQR 47-65) and 58 years (IQR 48-66), and the median duration of resuscitation was 58 (IQR 43-69) and 49 (IQR 33-71) minutes (p = 0.17). In a modified intention to treat analysis, 45 (32.4%) in the invasive and 29 (19.7%) patients in the standard arm survived to 180 days with a favourable neuro-logical outcome [absolute difference (AD), 95% CI: 12.7%, 2.6-22.7%, p = 0.015]. Forty-seven (33.8%) and 33 (22.4%) patients survived to 180 days [HR 0.59 (0.43-0.81); log rank test p = 0.0009]. At 30 days, 44 (31.7%) and 24 (16.3%) patients had favourable neurological outcome (AD 15.4%, 5.6-25.1%, p = 0.003), 60 (43.2%), and 46 (31.3%) patients had cardiac recovery (AD: 11.9%, 0.7-23%, p = 0.05), in the invasive and standard arms, respectively. The effect was larger in patients presenting with shockable rhythms (AD 18.8%, 7.6-29.4; p = 0.01; HR 2.26 [1.23-4.15]; p = 0.009) and prolonged CPR (>45 min; HR 3.99 (1.54-10.35); p = 0.005).Interpretation In patients with refractory OHCA, the invasive approach significantly improved 30-and 180-day neurologically favourable survival.

Extracorporeal cardiopulmonary resuscitation has been recognized as a promising therapy to restore circulation and increase survival in selected patients with refractory out-of-hospital cardiac arrest. A systematic approach is essential to achieve favorable results. In this chapter, we provide an overview of the key steps to achieve the best possible outcomes based on current evidence and the authors’ experience and highlights important gaps in knowledge that need to be addressed in future studies.

Fabry disease (FD) is a rare X‐linked lysosomal storage disorder with variable phenotypes, including neurological symptoms. These can be influenced by vascular impairment. Extracranial and transcranial vascular sonography is an effective and noninvasive method for measuring arterial structures and blood flow.

Aims Refractory out-of-hospital cardiac arrest (r-OHCA) in patients with pulmonary embolism (PE) is associated with poor outcomes. The role of extracorporeal cardiopulmonary resuscitation (ECPR) in this patient group is uncertain. This study aims to analyse clinical course, outcomes, and the effect of an invasive procedure, including ECPR, in a randomized population. Methods and results A post hoc analysis of a randomized controlled trial (Prague OHCA study) was conducted to evaluate the effect of ECPR vs. a standard approach in r-OHCA. A subgroup of patients with PE-related r-OHCA was identified, and procedural and outcome characteristics, including favourable neurological survival, organ donation, and complications, were compared to patients without PE. Pulmonary embolism was identified as a cause of r-OHCA in 24 of 256 (9.4%) enrolled patients. Patients with PE were more likely to be women [12/24 (50%) vs. 32/232 (13.8%); P < 0.001] and presented more frequently with an initial non-shockable rhythm [23/24 (95.8%) vs. 77/232 (33.2%); P < 0.001], as well as more severe acidosis at admission [median pH (interquartile range); 6.83 (6.75-6.88) vs. 6.98 (6.82-7.14); P < 0.001]. Their favourable 180-day neurological survival was significantly lower [2/24 (8.3%) vs. 66/232 (28.4%); P = 0.049], but the proportion of accepted organ donors was higher (16.7 vs. 4.7%, P = 0.04). Conclusion Refractory out-of-hospital cardiac arrest due to PE has a different presentation and inferior outcomes compared to other causes but may represent an important source of organ donations. The ECPR method did not improve patient outcomes.