Purpose of review Cardiogenic shock (CS) therapy involving catecholamines, inotropes, fluids and revascularization is often insufficient, and short-term mortality remains 50%. Different treatment algorithms and mechanical circulatory support devices (MCS) have been increasingly used in the treatment of CS. Coronavirus disease 2019 (COVID-19) pandemic is a major challenge faced by intensive care medicine providers inevitably influencing also CS management. Recent findings There is a lack of prospective data as well as international consensus regarding CS classification, patient risk stratification, and MCS use. Veno-arterial extracorporeal membrane oxygenation is considered the first line MCS in refractory CS and Impella the MCS of choice for the left ventricle unloading. Several ongoing randomized trials will provide much-needed evidence for MCS use in the coming years. COVID-19 infection is associated with several cardiovascular disorders complicated by CS and more data regarding the prevalence and mortality of CS during COVID-19 infection are needed. Summary This review summarizes current trends in the use of MCS in CS and discusses differences in CS management during the COVID-19 pandemic. Careful patient selection, early MCS initiation, and comprehensive intensive care by experienced team is key to successful outcome in patients with refractory CS.
Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Charles University Research program “Cooperatio - Cardiovascular Science”. Introduction Fabry disease (FD) is a multisystemic lysosomal storage disorder caused by a defect in the gene coding the alpha-galactosidase A enzyme. Cardiac involvement typically manifests as a phenocopy of hypertrophic cardiomyopathy. Three-dimensional echocardiography can analyze myocardial deformation of the left ventricle (LV) in both circumferential and longitudinal dimensions. Purpose We assessed 3D echocardiographic strain of the LV in FD patients in relation to heart failure severity, the presence of cardiovascular magnetic resonance (CMR) scar and long-term prognosis. Methods 3D echocardiography was feasible in 75/99 FD patients. Baseline natriuretic peptides and CMR late gadolinium enhancement were assessed together with long term outcome (death, heart failure decompensation or cardiovascular hospitalization) over a median follow-up of 3.1 years. Results The average age was 47 ± 14 years, 44% of patients were male and 51% expressed hypertrophy or concentric remodeling of the LV. Average LV ejection fraction (EF) was 65 ± 6%. A stronger correlation was observed for NTproBNP levels with 3D global longitudinal strain (GLS) (r = 0.49, p < 0.0001) than with 3D global circumferential strain (GCS) (r = 0.38, p < 0.001). LV EF by 3D weakly correlated with NTproBNP levels (r = 0.25, p = 0.036). Individuals with posterolateral scar on CMR had significantly lower local 3D circumferential strain at corresponding region (p = 0.008). 3D GLS was associated with long-term outcome (adjusted HR 0.84, CI 0.75, 0.95, p = 0.004) while 3D GCS was not (HR 0.94, CI 0.85 – 1.10, p = 0.284). 3D LV EF was not associated with long-term outcome. Conclusion 3D GLS is strongly associated with both heart failure severity measured as natriuretic peptides levels and long-term prognosis. Only borderline association of 3D GCS with HF severity and no association with prognosis was observed. Decreased local 3D CS reflects typical posterolateral scarring in FD. Where feasible, 3D-strain echocardiography can be used for comprehensive mechanical assessment of the LV in FD patients.
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.
Background: An increasing number of cardiac centres are using immediate percutaneous coronary intervention (PCI) and extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out of hospital cardiac arrest (r-OHCA). Published evidence regarding PCI in OHCA has been mainly reporting to patients with early return of spontaneous circulation and the influence of PCI and ECPR on survival in the population of patients with r-OHCA and acute coronary syndrome (ACS) remains unclear. Methods: In this post hoc analysis of the randomized r-OHCA trial, all patients with ACS as a cause of r-OHCA were included. The effect of successful PCI and ECPR on 180-days survival was examined using Kaplan-Meier estimates and multivariable Cox regression. Results: In total, 256 patients were evaluated in Prague OHCA study and 127 (49.6 %) had ACS as the cause of r-OHCA constituting current study population. The mean age was 58 years (46.3-64) and duration of resuscitation was 52.5 minutes (36.5-68). ECPR was used in 51 (40.2 %) of patients. Immediate PCI was performed in 86 (67.7%) patients and TIMI flow 2 or 3 was achieved in 75 (87.2%) patients. The overall 180-days survival of patients with successful PCI was 40 % compared to 7.7 % with no or failed immediate PCI (log-rank p < 0.001). After adjustment for confounders, successful PCI was associated with a lower risk of death (HR 0.47, CI 0.24-0.93, p = 0.031). Likewise, ECPR was associated with a lower risk of death (HR 0.11, CI 0.05-0.24, p< 0.001). Conclusion: In this post hoc analysis of the randomized r-OHCA trial, successful immediate PCI as well as ECPR were associated with improved 180-days survival in patients with r-OHCA due to ACS.
Complex Vascular Involvement in Fabry Disease: An Unusual Case of Combined Critical Lower Limb Ischemia and Deep Vein Thrombosis Fabry disease (FD) is an X-linked disorder of glycosphingolipid metabolism caused by a deficiency of the lysosomal enzyme α-galactosidase A. This results in progressive accumulation of glycolipids in a large spectrum of cells. Males with the classic form of FD suffer from cutaneous lesions (angiokeratomas), hypohidrosis, neuropathic pain, cardiomyopathy, renal function impairment, and premature cerebrovascular complications. We report an unusual case of a 63-year old male Fabry patient with critical ischemia and deep vein thrombosis of the lower limb. On the basis of this unusual case, we discuss the current data and gaps in knowledge regarding venous system disorders and peripheral arterial disease, as well as the question of “blood vessel fragility”, in Fabry patients.
Sevoflurane sample data in a standard single patient ICU room, VieCuri Medical Centre. Physical data of the ICU room: 52 m3, air refreshing rate minimum 6/hr
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.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.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 neurological 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).In patients with refractory OHCA, the invasive approach significantly improved 30- and 180-day neurologically favourable survival.None.
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.
BackgroundRefractory out-of-hospital cardiac arrest (OHCA) has a poor outcome. In patients, who cannot be rescued despite using advanced techniques like extracorporeal cardiopulmonary resuscitation (ECPR), organ donation may be considered. This study aims to evaluate, in refractory OHCA, how ECPR versus a standard-based approach allows organ donorship.MethodsThe Prague OHCA trial randomized adults with a witnessed refractory OHCA of presumed cardiac origin to either an ECPR-based or standard approach. Patients who died of brain death or those who died of primary circulatory reasons and were not candidates for cardiac transplantation or durable ventricle assist device were evaluated as potential organ donors by a transplant center. In this post-hoc analysis, the effect on organ donation rates and one-year organ survival in recipients was examined.ResultsOut of 256 enrolled patients, 75 (29%) died prehospitally or within 1 hour after admission and 107 (42%) during the hospital stay. From a total of 24 considered donors, 21 and 3 (p = 0.01) were recruited from the ECPR vs standard approach arm, respectively. Fifteen brain-dead and none cardiac-dead subjects were ultimately accepted, 13 from the ECPR and two from the standard strategy group. A total of 36 organs were harvested. The organs were successfully transplanted into 34 recipients. All transplanted organs were fully functional, and none of the recipients died due to graft failure within the one-year period post-transplant.ConclusionThe ECPR-based approach in the refractory OHCA trial is associated with increased organ donorship and an excellent outcome of transplanted organs.Trial registration: ClinicalTrials.gov Identifier: NCT 01511666. Registered January 19, 2012.
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