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

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

Hyperlactatemia and poor outcome After postcardiotomy veno-arterial extracorporeal membrane oxygenation: An individual patient data meta-Analysis.

INTRODUCTION: Postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) is associated with significant mortality. Identification of patients at very high risk for death is elusive and the decision to initiate V-A-ECMO is based on clinical judgment. The prognostic impact of pre-V-A-ECMO arterial lactate level in these critically ill patients has been herein evaluated. METHODS: A systematic review was conducted to identify studies on postcardiotomy VA-ECMO for the present individual patient data meta-analysis. RESULTS: Overall, 1269 patients selected from 10 studies were included in this analysis. Arterial lactate level at V-A-ECMO initiation was increased in patients who died during the index hospitalization compared to those who survived (9.3 vs 6.6 mmol/L, p < 0.0001). Accordingly, in hospital mortality increased along quintiles of pre-V-A-ECMO arterial lactate level (quintiles: 1, 54.9%; 2, 54.9%; 3, 67.3%; 4, 74.2%; 5, 82.2%, p < 0.0001). The best cut-off for arterial lactate was 6.8 mmol/L (in-hospital mortality, 76.7% vs. 55.7%, p < 0.0001). Multivariable multilevel mixed-effect logistic regression model including arterial lactate level significantly increased the area under the receiver operating characteristics curve (0.731, 95% CI 0.702-0.760 vs 0.679, 95% CI 0.648-0.711, DeLong test p < 0.0001). Classification and regression tree analysis showed the in-hospital mortality was 85.2% in patients aged more than 70 years with pre-V-A-ECMO arterial lactate level ≥6.8 mmol/L. CONCLUSIONS: Among patients requiring postcardiotomy V-A-ECMO, hyperlactatemia was associated with a marked increase of in-hospital mortality. Arterial lactate may be useful in guiding the decision-making process and the timing of initiation of postcardiotomy V-A-ECMO.

Short-term mechanical circulatory support in elderly patients.

BACKGROUND: Age over 70 years seems to confer poor prognosis for patients under mechanical circulatory support (MCS). Advanced age is usually a relative contraindication. Our objective was to assess the impact of age on survival of patients with short-term MCS. METHODS: Retrospective analysis of ≥70-year-old patients supported with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or Impella CP® due to cardiogenic shock and other situations of hemodynamic instability in a referral hospital (elderly group), compared with younger patients (<70 years). We analyze factors associated with survival in elderly group. RESULTS: Out of 164 short-term MCS implants from 2013 to October 2020, 45 (27.4%) correspond to ≥70-year-old patients (73.3% VA-ECMO; 26.7% Impella CP®), 80% as bridge to recovery and 15.6% for high-risk percutaneous coronary intervention (PCI). We found no significant differences in complications developed between both groups. Survivals at discharge (40% vs. 43.7%, p = 0.403) and at follow-up (median 13.6 [30] months) were similar in elderly and young patients (35.6% vs. 37.8%, log-rank p = 0.061). Predictive factors of mortality in elderly patients were peripheral artery disease (p = 0.037), higher lactate (p = 0.003) and creatinine (p = 0.035) at implant, longer cardiac arrest (p = 0.003), and worse post-implantation left ventricular ejection fraction (p = 0.003). Patients with indication of MCS for high-risk PCI had higher survival compared to other indications (p = 0.013). CONCLUSION: Short-term MCS with VA-ECMO or Impella CP® in elderly patients may be a reasonable option in hemodynamic compromise situations as bridge to recovery or elective high-risk PCI, without a significant increase in complications or mortality. Age should not be an absolute contraindication, but careful selection of candidate patients is necessary.

Predictive Model and Risk Score for In-Hospital Mortality in Patients with All-Cause Cardiogenic Shock.

Cardiogenic shock (CS) is a condition associated with high morbidity and mortality. Our study aimed to perform a risk score for in-hospital mortality that allows for stratifying the risk of death in patients with CS.This is a retrospective analysis, which included 135 patients from a Spanish university hospital between 2011 and 2020. The Santiago Shock Score (S3) was created using clinical, analytical, and echocardiographic variables obtained at the time of admission.The in-hospital mortality rate was 41.5%, and acute coronary syndrome (ACS) was the responsible cause of shock in 60.7% of patients. Mitral regurgitation grade III-IV, age, ACS etiology, NT-proBNP, blood hemoglobin, and lactate at admission were included in the score. The S3 had good accuracy for predicting in-hospital mortality area under the receiver operating characteristic curve (AUC) 0.85 (95% confidence interval (CI) 0.78-0.90), higher than the AUC of the CardShock score, which was 0.74 (95% CI 0.66-0.83). Predictive power in a cohort of 131 patients with profound CS was similar to that of CardShock with an AUC of 0.601 (95% CI 0.496-0.706) versus an AUC of 0.558 (95% CI 0.453-0.664). Three risk categories were created according to the S3: low (scores 0-6), intermediate (scores 7-10), and high (scores 11-16) risks, with an observed mortality of 12.9%, 49.1%, and 87.5% respectively (P < 0.001).The S3 score had excellent predictive power for in-hospital mortality in patients with nonprofound CS. It could aid the initial risk stratification of patients and thus, guide treatment and clinical decision making in patients with CS.

Predictors of cardiovascular events and all-cause of death in patients with transfusion-dependent myelodysplastic syndrome.

Cardiovascular disease (CVD) involves the second cause of death in low-risk myelodysplastic syndrome (MDS) population. Prospective study to characterise the CVD and to identify predictors for the combined event (CE) cardiovascular event and/or all-cause mortality in transfusion dependent low-risk MDS patients. Thirty-one patients underwent a cardiac assessment including biomarkers and cardiac magnetic resonance (cMR) with parametric sequences (T1, T2 and T2* mapping) and myocardial deformation by feature tracking (FT) and were analysed for clonal hematopoiesis of indeterminate potential mutations. Cardiac assessment revealed high prevalence of unknown structural heart disease (51% cMR pathological findings). After 2·2 [0·44] years follow-up, 35·5% of patients suffered the CE: 16% death, 29% cardiovascular event. At multivariate analysis elevated NT-proBNP ≥ 486pg/ml (HR 96·7; 95%-CI 1·135-8243; P = 0·044), reduced native T1 time < 983ms (HR 44·8; 95%-CI 1·235-1623; P = 0·038) and higher left ventricular global longitudinal strain (LV-GLS) (HR 0·4; 95%-CI 0·196-0·973; P = 0·043) showed an independent prognostic value. These variables, together with the myocardial T2* time < 20ms, showed an additive prognostic value (Log Rank: 12·4; P = 0·001). In conclusion, low-risk MDS patients frequently suffer CVD. NT-proBNP value, native T1 relaxation time and longitudinal strain by FT are independent predictors of poor cardiovascular prognosis, thus, their determination would identify high-risk patients who could benefit from a cardiac treatment and follow-up.

Levosimendan in veno-arterial extracorporeal membrane oxygenator supported patients: Impact on the success of weaning and survival.

Weaning failure and mortality rates in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) supported patients are significant. Small studies suggest the possible usefulness of levosimendan in this environment, especially in postcardiotomy shock. We performed a retrospective analysis of VA-ECMO implants in a referral hospital comparing weaning failure and survival of patients treated with levosimendan with a control group. From 2013 to May 2020, 123 VA-ECMO for several indications were implanted. Levosimendan was administered in 23 patients (18.7%) with good tolerance. Levosimendan was used more frequently in cardiogenic shock due to acute coronary syndrome indication, and in patients with lower left ventricular ejection fraction (LVEF) at the implant. No significant differences were found in success of ECMO weaning (60.9% levosimendan group vs. 44% non-levosimendan group, P = .169) despite worse LVEF in levosimendan group. Survival at follow-up (20.6 [58] months) was higher in the group that received levosimendan, although without finding statistically significant differences (47.8% vs. 32.0%, log rank P = .124). Levosimendan can be safely administered during VA-ECMO support. Patients receiving levosimendan were weaned similarly from circulatory support despite worse LVEF. Its use did not influence in short- and medium-term survival. Randomized studies are needed to evaluate the levosimendan impact in this indication.

External validation of the PC-ECMO score in postcardiotomy veno-arterial extracorporeal membrane oxygenation.

Reliable stratification of the risk of early mortality after postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) remains elusive. In this study, we externally validated the PC-ECMO score, a specific risk scoring method for prediction of in-hospital mortality after postcardiotomy V-A-ECMO. Overall, 614 patients who required V-A-ECMO after adult cardiac surgery were gathered from an individual patient data meta-analysis of nine studies on this topic. The AUC of the logistic PC-ECMO score in predicting in-hospital mortality was 0.678 (95%CI 0.630-0.726; p < 0.0001). The AUC of the logistic PC-ECMO score in predicting on V-A-ECMO mortality was 0.652 (95%CI 0.609-0.695; p < 0.0001). The Brier score of the logistic PC-ECMO score for in-hospital mortality was 0.193, the slope 0.909, the calibration-in-the-large 0.074 and the expected/observed mortality ratio 0.979. 95%CIs of the calibration belt of fit relationship between observed and predicted in-hospital mortality were never above or below the bisector (p = 0.072). The present findings suggest that the PC-ECMO score may be a valuable tool in clinical research for stratification of the risk of patients requiring postcardiotomy V-A-ECMO.

Inter-institutional analysis of the outcome after postcardiotomy veno-arterial extracorporeal membrane oxygenation.

INTRODUCTION: Patients requiring postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) have a high risk of early mortality. In this analysis, we evaluated whether any interinstitutional difference exists in the results of postcardiotomy V-A-ECMO. METHODS: Studies on postcardiotomy V-A-ECMO were identified through a systematic review for individual patient data (IPD) meta-analysis. Analysis of interinstitutional results was performed using direct standardization, estimation of observed/expected in-hospital mortality ratio and propensity score matching. RESULTS: Systematic review of the literature yielded 31 studies. Data from 10 studies on 1269 patients treated at 25 hospitals were available for the present analysis. In-hospital mortality was 66.7%. The relative risk of in-hospital mortality was significantly higher in six hospitals. Observed versus expected in-hospital mortality ratio showed that four hospitals were outliers with significantly increased mortality rates, and one hospital had significantly lower in-hospital mortality rate. Participating hospitals were classified as underperforming and overperforming hospitals if their observed/expected in-hospital mortality was higher or lower than 1.0, respectively. Among 395 propensity score matched pairs, the overperforming hospitals had significantly lower in-hospital mortality (60.3% vs 71.4%, p = 0.001) than underperforming hospitals. Low annual volume of postcardiotomy V-A-ECMO tended to be predictive of poor outcome only when adjusted for patients' risk profile. CONCLUSIONS: In-hospital mortality after postcardiotomy V-A-ECMO differed significantly between participating hospitals. These findings suggest that in many centers there is room for improvement of the results of postcardiotomy V-A-ECMO.

Cardiogenic shock code 2023. Expert document for a multidisciplinary organization that allows quality care.

Despite the efforts made to improve the care of cardiogenic shock (CS) patients, including the development of mechanical circulatory support (MCS), the prognosis of these patients continues to be poor. In this context, CS code initiatives arise, based on providing adequate, rapid, and quality care to these patients. In this multidisciplinary document we try to justify the need to implement the SC code, defining its structure/organization, activation criteria, patient flow according to care level, and quality indicators. Our specific purposes are: a) to present the peculiarities of this condition and the lessons of infarction code and previous experiences in CS; b) to detail the structure of the teams, their logistics and the bases for the management of these patients, the choice of the type of MCS, and the moment of its implantation, and c) to address challenges to SC code implementation, including the uniqueness of the pediatric SC code. There is an urgent need to develop protocolized, multidisciplinary, and centralized care in hospitals with a large volume and experience that will minimize inequity in access to the MCS and improve the survival of these patients. Only institutional and structural support from the different administrations will allow optimizing care for CS.

Echocardiographic Prediction of Successful Weaning From Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Weaning from venoarterial extracorporeal membrane oxygenation (VA-ECMO) support fails in 30% to 70% of patients. OBJECTIVE: To explore the utility of echocardiographic parameters in predicting successful disconnection from VA-ECMO. METHODS: Patients receiving VA-ECMO in a referral hospital were included. The relationships between echocardiographic parameters during the weaning trial and weaning success (survival > 24 hours after VA-ECMO explant and no death from cardiogenic shock, heart failure, or cardiac arrest during the hospital stay) and survival were evaluated. RESULTS: Of 85 patients included, 61% had successful weaning. Parameters significantly related to weaning success were higher left ventricular ejection fraction (LVEF; 40% in patients with weaning success vs 30% in patients with weaning failure, P = .01), left ventricular outflow tract velocity time integral (15 cm vs 11 cm, P = .01), aortic valve opening in every cycle (98% vs 91% of patients, P = .01), and normal qualitative right ventricular function (60% vs 42% of patients, P = .02). The LVEF remained as an independent predictor of weaning success (hazard ratio, 0.938; 95% CI, 0.888-0.991; P = .02). An LVEF >33.4% was the optimal cutoff value to discriminate patients with successful weaning (area under the curve, 0.808; sensitivity, 93%; specificity, 72%) and was related to higher survival at discharge (60% vs 20%, P < .001). CONCLUSION: Among weaning trial echocardiographic parameters, LVEF was the only independent predictor of successful VA-ECMO weaning. An LVEF >33.4% was the optimal cutoff value to discriminate patients with successful weaning and was related to final survival.

Central versus Peripheral Postcardiotomy Veno-Arterial Extracorporeal Membrane Oxygenation: Systematic Review and Individual Patient Data Meta-Analysis.

BACKGROUND: It is unclear whether peripheral arterial cannulation is superior to central arterial cannulation for postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: A systematic review was conducted using PubMed, Scopus, and Google Scholar to identify studies on postcardiotomy VA-ECMO for the present individual patient data (IPD) meta-analysis. Analysis was performed according to the intention-to-treat principle. RESULTS: The investigators of 10 studies agreed to participate in the present IPD meta-analysis. Overall, 1269 patients were included in the analysis. Crude rates of in-hospital mortality after central versus peripheral arterial cannulation for VA-ECMO were 70.7% vs. 63.7%, respectively (adjusted OR 1.38, 95% CI 1.08-1.75). Propensity score matching yielded 538 pairs of patients with balanced baseline characteristics and operative variables. Among these matched cohorts, central arterial cannulation VA-ECMO was associated with significantly higher in-hospital mortality compared to peripheral arterial cannulation VA-ECMO (64.5% vs. 70.8%, p = 0.027). These findings were confirmed by aggregate data meta-analysis, which showed that central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation (OR 1.35, 95% CI 1.04-1.76, I2 21%). CONCLUSIONS: Among patients requiring postcardiotomy VA-ECMO, central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation. This increased risk is of limited magnitude, and further studies are needed to confirm the present findings and to identify the mechanisms underlying the potential beneficial effects of peripheral VA-ECMO.

Post-traumatic stress disorder symptoms after veno-arterial extracorporeal membrane oxygenator support.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a common long-term outcome after intensive care of critical illness. OBJECTIVES: Assess the prevalence and factors associated to PTSD after veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. METHODS: Retrospective analysis of admission data and cross-sectional assessment of PTSD symptoms in adult survivors from admission requiring VA-ECMO support in a referral hospital. People were screened through abbreviated Impact of Event Scale-6 (IES-6). RESULTS: Out of 135 VA-ECMO implants performed from 2013 to 2020, 48 (35.6%) patients survived the admission. After a median follow-up of 31.4 [36] months, 34 survivors responded the questionnaire. All patients required sedation and invasive mechanical ventilation. Up to 29.4% of patients had PTSD symptoms. Patients with altered IES-6 items had passed a longer time since admission in ICCU (44±15 vs 30±20 months, p = 0.034). No baseline characteristic or admission-related variables were correlated with IES-6 except the lower time under mechanical ventilation (6.5 [8.5] vs. 8.5 [21] days, p = 0.044). CONCLUSIONS: Survivors from admission requiring VA-ECMO support show high prevalence of PTSD symptoms, appearing more frequently when more time has elapsed since admission. Special attention should be paid to psychological symptoms after VA-ECMO support.

Magnetic Resonance Myocardial Feature Tracking in Transfusion-Dependent Myelodysplastic Syndrome.

BACKGROUND: Myocardial deformation with echocardiography allows early detection of systolic dysfunction and is related to myocardial iron overload (MIO) determined by T2* in hereditary anemias under transfusion support. Our aim was to analyze the diagnostic and prognostic usefulness of magnetic resonance feature tracking (MR-FT) myocardial strain in low-risk myelodysplastic syndromes (LR-MDS) patients. METHODS: Prospective study in transfusion-dependent LR-MDS patients and healthy controls who underwent a cardiac MR-FT. We analyzed the relationships between strain MR-FT and iron overload parameters and its prognostic impact in cardiovascular events and/or death. RESULTS: Thirty-one patients and thirteen controls were included. MIO (T2* < 20 ms) was detected in 9.7% of patients. Left ventricular global longitudinal strain (LV-GLS) by MR-FT was pathological (> -19.3%) in 32.3% of patients. Less negative strain values correlated with lower T2* (R = -0.37, p = 0.033) and native myocardial T1 (R = -0.39, p = 0.031) times. LV-GLS by MR-FT was significantly associated with higher incidence of the combined cardiovascular events and/or all-cause death (p = 0.047), with a cut-off value of -17.7% for predicting them (63% sensitivity and 81% specificity, area under the curve = 0.69). After adjusting analysis including demographic, biomarkers and imaging variables, a higher LV-GLS value by MR-FT remained as predictor of combined event in transfusion-dependent LR-MDS patients (hazard ratio, 0.4; confidence interval, 0.15-0.98; p = 0.045). CONCLUSIONS: Longitudinal myocardial strain by MR-FT in LR-MDS patients is associated to MIO and correlates with adverse events in the follow-up, what could serve as a prognostic tool.

A rare HCN4 variant with combined sinus bradycardia, left atrial dilatation, and hypertrabeculation/left ventricular noncompaction phenotype.

INTRODUCTION AND OBJECTIVES: HCN4 variants have been reported to cause combined sick sinus syndrome (SSS) and left ventricular noncompaction (LVNC) cardiomyopathy. This relationship has been proven in few cases and no previous patients have associated left atrial dilatation (LAD). Our objective was to study a familial disorder characterized by SSS, LAD, and hypertrabeculation/LVNC and to identify the underlying genetic and electrophysiological characteristics. METHODS: A family with SSS and LVNC underwent a clinical, genetic, and electrophysiological assessment. They were studied via electrocardiography, Holter recording, echocardiography, and exercise stress tests; cardiac magnetic resonance imaging was additionally performed in affected individuals. Genetic testing was undertaken with targeted next-generation sequencing, as well as a functional study of the candidate variant in Chinese hamster ovary cells. RESULTS: Twelve members of the family had sinus bradycardia, associated with complete criteria of LVNC in 4 members and hypertrabeculation in 6 others, as well as LAD in 9 members. A HCN4 c.1123C>T;(p.R375C) variant was present in heterozygosis in all affected patients and absent in unaffected individuals. Electrophysiological analyses showed that the amplitude and densities of the HCN4 currents (IHCN4) generated by mutant p.R375C HCN4 channels were significantly lower than those generated by wild-type channels. CONCLUSIONS: The combined phenotype of SSS, LAD, and LVNC is associated with the heritable HCN4 c.1123C>T;(p.R375C) variant. HCN4 variants should be included in the genetic diagnosis of LVNC cardiomyopathy and of patients with familial forms of SSS, as well as of individuals with sinus bradycardia and LAD.

Progressive spontaneous coronary artery dissection secondary to fibromuscular dysplasia requiring mechanical circulatory support.

Spontaneous coronary artery dissection (SCAD) usually appears as an acute coronary syndrome with good prognosis. We present the case of a 39-year-old woman with progressive SCAD secondary to fibromuscular dysplasia with catastrophic course. The patient required several mechanical circulatory support systems including a left ventricular assist device (CentriMag®, Thoratec, Pleasanton, CA, USA) as bridge to recovery. .