Ventricular fibrillation/ventricular tachycardia within 72 h of VA-ECMO: incidence, outcomes, risk factors, and management.

AIMS: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an important technique for the treatment of refractory cardiogenic shock and cardiac arrest; however, the early management of ventricular fibrillation/ventricular tachycardia (VF/VT), within 72 h of VA-ECMO, and its effects on patient prognosis remain unclear. METHODS AND RESULTS: We retrospectively analysed patients at the First Affiliated Hospital of Nanjing Medical University who underwent VA-ECMO between January 2017 and March 2022. The patients were divided into two groups, VF/VT and nVF/VT, based on whether or not VF/VT occurred within 72 h after the initiation of VA-ECMO. We utilized logistic regression analysis to evaluate the independent risk factors for VF/VT in patients undergoing VA-ECMO and to ascertain whether the onset of VF/VT affected 28 day survival rate, length of intensive care unit stay, and/or other clinical prognostic factors. Subgroup analysis was performed for the VF/VT group to determine whether defibrillation affected prognosis. In the present study, 126 patients were included, 65.87% of whom were males (83/126), with a mean age of 46.89 ± 16.23, a 28 day survival rate of 57.14% (72/126), an incidence rate of VF/VT within 72 h of VA-ECMO initiation of 27.78% (35/126), and 80% of whom (28/35) received extracorporeal cardiopulmonary resuscitation. The incidence of VF/VT resulting from cardiac arrest at an early stage was significantly higher than that of refractory cardiogenic shock (80% vs. 20%; P = 0.022). The restricted cubic spline model revealed a U-shaped relationship between VF/VT incidence and initial heart rate (iHR), and multivariate logistic regression analysis showed that an iHR > 120 b.p.m. [odds ratio (OR) 6.117; 95% confidence interval (CI) 1.672-22.376; P = 0.006] and hyperlactataemia (OR 1.125; 95% CI 1.016-1.246; P = 0.023) within 1 h of VA-ECMO initiation were independent risk factors for the occurrence of VF/VT. VF/VT was not found to be associated with the 28 day survival of patients undergoing VA-ECMO support, nor did it affect other secondary endpoints. Defibrillation did not alter the overall prognosis in patients with VF/VT during VA-ECMO. CONCLUSIONS: An iHR > 120 b.p.m. and hyperlactataemia were independent risk factors for the occurrence of VF/VT within 72 h of VA-ECMO initiation. The occurrence of VF/VT does not affect, nor does defibrillation in these patients improve the overall patient prognosis. TRIAL REGISTRATION: ChiCTR1900026105.

Hospital­acquired pneumonia caused by Kodamaea ohmeri during extracorporeal membrane oxygenation treatment: A case report and literature review.

Kodamaea ohmeri (K. ohmeri) is an ascosporogenic species of yeast that belongs to the genus Ascosporogenous and the family of Saccharomycetaceae. It has recently been found to cause various types of infections, particularly in critically ill immunocompromised patients. The present study describes a case of hospital-acquired pneumonia caused by K. ohmeri during veno-arterial extracorporeal membrane oxygenation. The fungal culture turned negative after the administration of caspofungin and amphotericin B. Extracorporeal membrane oxygenation (ECMO) is an adjunctive medical technique that provides temporary cardiopulmonary support for patients. Previous observations have suggested that the immune function of patients will typically decline during the use of ECMO, rendering infection to be one of the main complications of ECMO. K. ohmeri is a rare pathogenic fungus, particularly in immunocompromised individuals with vascular catheters, while amphotericin B is the most common antifungal therapy administered to treat K. ohmeri infections. It is important to raise awareness of rare fungal infections and actively treat them.

The correlation between early net fluid balance and the clinical outcomes of patients receiving extracorporeal cardiopulmonary resuscitation.

OBJECTIVE: To investigate correlation between early net fluid balance and the clinical outcomes of patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: Adult patients on ECPR admitted to the Department of Emergency in the First Affiliated Hospital of Nanjing Medical University from May 2015 to December 2020 were included. Net fluid balance for consecutive 4 days after ECPR was recorded. The primary outcome was survival to intensive care unit (ICU) discharge. We used multivariable logistic regression to assess the association between fluid status and clinical outcomes. RESULTS: A total of 72 patients were enrolled and divided into two groups: the survivor group and the non-survivor group. The overall rate of survival to ICU discharge was 44.4%. Daily fluid balance (DFB) in the survivor group was lower than that in the non-survivor group at day 4 (-11.47 (-19.74, 8.7) vs. -5.08 (-12.94, 13.9) mL/kg, P=0.046), as was cumulative fluid balance (CFB) over the first 4 days (-36.03 (-51.45, 19.03) vs. -7.22 (-32.79, 21.02) mL/kg, P=0.009). Both continuous renal replacement therapy (CRRT) and CFB from days 1-4 were significantly correlated with survival to ICU discharge (OR=14.617, 95% CI: 1.344, 48.847, P=0.028; OR=1.261, 95% CI: 1.091, 1.375, P=0.003, respectively). CFB from days 1-4 was determined to have a roughly linear association with the log odds of survival to ICU discharge. CONCLUSION: Early negative fluid balance maybe associated with survival to ICU discharge in patients receiving ECPR.

The neuro-prognostic value of the ion shift index in cardiac arrest patients following extracorporeal cardiopulmonary resuscitation.

BACKGROUND: The ion shift index (ISI) as a prognostic indicator that can show the severity of hypoxic-ischemic injury. We aimed to evaluate the performance of the ISI in predicting unfavorable neurological outcomes at hospital discharge in cardiac arrest (CA) patients following extracorporeal cardiopulmonary resuscitation (ECPR) and to compare its performance to other prognostic predictors. METHODS: This was a retrospective observational study including adult CA patients treated with ECPR between January 2018 and December 2022 in a tertiary hospital. Data regarding clinical characteristics and laboratory parameters were collected from medical records. The ISI was determined based on the first available serum electrolyte levels after ECPR. The primary outcome was unfavorable neurological status at hospital discharge, defined as Cerebral Performance Categories 3-5. Comparisons of the characteristics between the two groups were made using the χ2 test for categorical variables and the t-test or non-parametric Mann-Whitney U-test for continuous variables, as appropriate. Correlation analysis was performed using Spearman's rank correlation coefficient. A two-tailed P-value <0.05 was considered statistically significant. RESULTS: Among the 122 patients involved, 46 (37.7%) had out-of-hospital CA, and 88 had unfavorable neurological outcomes. The ISI was significantly higher in the unfavorable outcome group than in the favorable outcome group (3.74 [3.15-4.57] vs. 2.69 [2.51-3.07], P<0.001). A higher ISI level was independently related to unfavorable outcome (odds ratio=6.529, 95% confidence interval 2.239-19.044, P=0.001). An ISI level >3.12 predicted unfavorable outcomes with a sensitivity and specificity of 74.6% and 85.2%, respectively (P<0.001). The prognostic performance of ISI (area under the curve [AUC]=0.887) was similar to that of other predictors, such as gray-to-white matter ratio (AUC=0.850, P=0.433) and neuron-specific enolase (AUC=0.925, P=0.394). CONCLUSION: ISI may be used as a prognostic biomarker to predict neurological outcomes in CA patients following ECPR.

Randomized controlled trial of ultra-protective vs. protective ventilation strategy in veno-arterial extracorporeal membrane oxygenation patients with refractory cardiogenic shock: a study protocol for the ultra-ECMO trial.

Background: A protective or ultra-protective tidal volume strategy is widely applied to patients with acute respiratory distress syndrome (ARDS). The use of very low tidal volume has the potential to further redece ventilation-induced lung injury (VILI) comparde with a "normal" lung protective management. Plus, cardiogenic pulmonary edema (CPE) caused by hydrostatic mechanisms in patients with cardiogenic shock has similar respiratory mechanics to those found in patients with ARDS. And no consensus exists on mechanical ventilation parameter settings in patients with VA-ECMO. The study aimed to investigate the impact of an ultra-protective tidal volume strategy on the 28-day ventilator-free day (VFD) number in VA-ECMO-supported patients with refractory cardiogenic shock, including cardiac arrest. Methods: The Ultra-ECMO trial is a randomized controlled, open-label, single-center prospective superiority trial. At the onset of ECMO initiation, we will divide patients randomly into an intervention group and a control group in a 1:1 ratio. The control group will adopt protective ventilation settings [initial tidal volume: 6 ml/kg of predicted body weight (PBW)] for ventilation, and the intervention group will adopt ultra-protective ventilation settings (initial tidal volume: 4 ml/kg of PBW) for ventilation. The procedure is expected to last 72 h, after which the ventilator settings will be at the intensivists' discretion. The primary outcome is the VFD number at 28 days after inclusion. The secondary outcomes will include respiratory mechanics; analgesic/sedation dosage; lung ultrasound score; interleukin-6, interleukin-8, and monocyte chemotactic protein-1 levels in broncho-alveolar lavage fluid at the moment of enrollment (T0), 24, 48, and 72 h (T1, T2, and T3, respectively) after ECMO initiation; total time (in days) required for ECMO weaning; length of stay in the intensive care unit; total cost of hospitalization; amounts of resuscitative fluids; and in-hospital mortality. Discussion: VA-ECMO-treated patients without ARDS possess abnormal lung function. CPE, thoracic compliance reduction, and poor pulmonary blood perfusion are frequently present, and these patients can more easily progress to ARDS. It seems that targeting the protective tidal volume can lower adverse outcome incidence rates, even in patients without ARDS. This trial seeks to answer the question of whether adopting an ultra-protective tidal volume strategy can lead to superior primary and secondary outcomes compared to adopting a protective tidal volume strategy in patients treated by VA-ECMO. The Ultra-ECMO trial will provide an innovative mechanical ventilation strategy for VA-ECMO-supported patients for improving treatment outcomes at biological and potentially clinical levels. Clinical Trial Registration: ChiCTR2200067118.

Protection of Oxygen Glucose Deprivation-Induced Human Brain Vascular Pericyte Injury: Beneficial Effects of Bellidifolin in Cellular Pyroptosis.

Pericytes play critical roles in the maintenance of brain vascular homeostasis. However, very little is currently known about how pericytes regulate ischemic stroke-induced brain injury. Inflammation is a key event in the pathobiology of stroke, in which the nod-like receptor protein-3 (NLRP3) inflammasome is involved in, triggering sterile inflammatory responses and pyroptosis. In the current study, an immortalized cell line derived from human brain vascular pericytes (HBVPs) was constructed, and it showed that HBVPs challenged with oxygen glucose deprivation (OGD) displays pronounced cellular excretion of LDH, IL-1ß, IL-18 and increased PI positive staining. Mechanistically, upon OGD treatment, NLRP3 forms an inflammasome with its adaptor protein apoptosis-associated speck-like protein, containing a caspase recruitment domain (ASC) and caspase-1, manifested as much more co-stainings of NLRP3, ASC and Caspase-1 in HBVPs, accompanied by the increased protein levels of NLRP3, ASC, caspase-1 as well as the pyroptosis-associated protein gasdermin D (GSDMD). Intriguingly, GSDMD-N shuttled to the mitochondrial membrane triggered by OGD exposure, which promoted massive mitochondria-derived ROS generation. Importantly, the invention value of the specific targets was evaluated by treatment with bellidifolin, a kind of ketone compound derived from Swertia chirayita in traditional Tibetan medicine. It showed that bellidifolin exerts beneficial effects and attenuates the formation of NLRP3/ASC/Caspase-1 complex, thereby impeding GSDMD-N shuttling and resultant ROS generation, protecting against OGD-induced HBVPs pyroptosis. Overall, these findings unravel the potential mechanisms of pericyte injury induced by OGD and indicate that bellidifolin may exert its beneficial effects on pyroptosis, thus providing new therapeutic insights into stroke.

A novel loss-of-function mutation in NRAP is associated with left ventricular non-compaction cardiomyopathy.

Background: The nebulin-related-anchoring protein (NRAP) gene encodes actin-associated ankyrin. Few studies reported the association of the NRAP gene with cardiomyopathy. Thus, the genetic role of this gene in cardiomyopathy remains to be investigated. Methods: The clinical data of the rare case of left ventricular non-compaction (LVNC) were collected and analyzed. Whole-exome sequencing (WES) was performed on related family members. Western blot was used to detect the effect of mutation on the NRAP protein expression. The effect of the c.259delC variant on myocardial development was further evaluated in a zebrafish model. Results: A novel homozygous frameshift mutation c.259delC of NRAP was found in the proband with LVNC. It was found that c.259delC decreased the expression of NRAP by Western blot. In the zebrafish model, the heart development was affected while knocking out the NRAP gene, which showed pericardial edema. The pathological manifestations were uneven hypertrophy, disordered arrangement of cardiomyocytes, enlarged intercellular space, and loose muscle fibers. RNA-sequencing (RNA-seq) showed that the expression of genes related to heart development decreased significantly, and the NRAP gene mutation could participate in biological processes (BPs) such as myocardial contraction, cell adhesion, myosin coarse filament assembly of striated muscle, myosin complex composition, and muscle α-actin binding. Conclusion: We identified a rare case of LVNC associated with a novel homozygous NRAP frameshift variant. This study further strengthened the evidence linking mutations in the NRAP gene with LVNC, providing a new clue for further study of LVNC. NRAP may be one of the pathogenic genes of cardiomyopathy.

Timing of brain computed tomography for predicting neurological prognosis in comatose cardiac arrest survivors: a retrospective observational study.

BACKGROUND: To assess the association between relevant brain computed tomography (CT) parameters at different time and neurological prognosis in adult comatose survivors after cardiac arrest (CA). METHODS: A total of 94 CA patients who underwent early and late CT scans (within 24 h and 24 h to 7 d respectively after CA) between January 2018 and April 2020 were enrolled in this retrospective study. According to the Cerebral Performance Category (CPC) score at hospital discharge, the patients were divided into either a good outcome (CPC 1-2) group or a poor-outcome group (CPC 3-5). The grey-to-white matter ratio (GWR) and the proportion of cerebrospinal fluid volume (pCSFV) were measured. In predicting poor outcomes, the prognostic performance of relevant CT parameters was evaluated, and the comparison analysis (expressed as the ratio of parameters in late CT to those in the early CT) of different CT time was conducted. RESULTS: Totally 26 patients were in the good-outcome group, while 68 patients were in the poor-outcome group. The putamen density, GWR, and pCSFV in late CT were significantly lower in the poor-outcome group (P<0.05). The ratios of GWR and pCSFV in the poor-outcome group were significantly decreased according to comparison analysis of different CT time (P<0.05), while there was no significant difference in the ratio of putamen density. GWR-basal ganglia <1.18 in late CT showed the best predictive value. The ratio of pCSFV <0.98 predicted unfavorable neurological outcomes with a sensitivity of 65.9% and a specificity of 93.8% (P=0.001). CONCLUSIONS: Brain CT performed >24 h after CA may be a good choice as a neuroimaging approach to evaluating prognosis. To predict neurological prognosis, comparison analysis of different CT time can be used as another promising tool in comatose CA survivors.

Clinical observation of different targeted temperature management methods in patients with cardiac arrest.

OBJECTIVE: To explore the clinical value of extracorporeal cardiopulmonary resuscitation (ECPR) combined with different targeted temperature management (TTM) for the treatment of cardiac arrest. METHODS: From January 2018 to September 2020, ECPR was initiated in patients with cardiac arrest who did not have their spontaneous circulation restored after 20 minutes of traditional cardiopulmonary resuscitation (CPR). A total of 22 patients (observation group) given TTM were treated with Hico-variotherm 550 (HU 550) and 30 patients (control group) not given TTM were treated with a medical water circulation cooling blanket. The Glasgow Coma scale (GCS) score, serum neuron-specific enolase (NSE), survival rate and neurological prognosis after ECMO weaning were compared between the two groups. RESULTS: There was no significant difference between the two groups in GCS score on the third and seventh days after resuscitation and serum NSE on the first and third day after treatment (P>0.05). Compared with the control group, the survival rate (40.91% vs 33.33%) and favorable neurological outcome (36.36% vs 26.67%) of patients in the observation group were slightly higher, but the differences were not statistically significant (all P>0.05). The incidence of shivering and body temperature fluctuation during rewarming in the observation group was lower than that in the control group (P<0.05). CONCLUSION: HU550 poikilothermia water cabinet combined with ECMO can better control the targeted temperature of patients in a more accurate range and improve the survival rate; however, it exerts no statistical improvement in the incidence of complications.

Generation of patient-derived IPSC lines from a girl with Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) caused by compound heterozygous GTPBP3 variants.

Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) caused by mutations in GTPBP3 gene is a rare mitochondrial disease. The patient-derived PBMCs of sibling with the compound heterozygous variants in GTPBP3 (NM_133644): c.1289G>A(p.Cys430Tyr); c.545G>A(p.Gly182Glu) were reprogrammed into induced pluripotent stemcell (iPSC) lines (DPNJMUi001-A.) using non-integrative Sendai virus. The COXPD23 iPSC lines present normal karyotypes, high expression of pluripotency markers and the capacity to differentiate into cells of all three germ layers.

Case report: Rare novel MIPEP compound heterozygous variants presenting with hypertrophic cardiomyopathy, severe lactic acidosis and hypotonia in a Chinese infant.

Background: Mitochondrial intermediate peptidase, encoded by the MIPEP gene, is involved in the processing of precursor mitochondrial proteins related to oxidative phosphorylation. Only a few studies have shown that mutations in MIPEP can cause combined oxidative phosphorylation deficiency-31 (COXPD31), an autosomal recessive multisystem disorder associated with mitochondrial dysfunction. We report herein a rare case of an 8-month-old boy in China with hypertrophic cardiomyopathy (HCM), severe lactic acidosis, and hypotonia caused by novel MIPEP compound heterozygous variants. Methods: Trio-whole-exome sequencing and copy number variation sequencing were performed to identify mutated genetic loci. Sanger sequencing and quantitative real-time PCR were used to validate the candidate single nucleotide variants and copy number variants, respectively. Results: The proband was an 8-month-old boy with HCM, severe lactic acidosis, and hypotonia who died 2 months after his first admission. Two novel compound heterozygous variants, c.1081T > A (p. Tyr361Asn) and a whole deletion (Ex1-19 del), were found in the MIPEP gene, which were inherited from his healthy parents respectively. Additionally, his mitochondria DNA copy number was significantly reduced. Conclusion: We are the first to report a patient with rare MIPEP variants in China. Our findings expand the mutation spectrum of MIPEP, and provide insights into the genotype-phenotype relationship in COXPD31.

Derivation and validation of the CANP scoring model for predicting the neurological outcome in post-cardiac arrest patients.

OBJECTIVES: To establish and validate a prognostic scoring model in a Chinese population to predict the neurological outcome among comatose survivors of cardiac arrest (CA). METHODS: 159 CA patients between January 2016 and November 2020 were recruited in this retrospective study. In the derivation cohort, prognostic factors available from arrest circumstances and early in-hospital indicators were measured. The Cardiac Arrest Neurological Prognosis (CANP) score was then constructed to predict unfavorable outcomes at 30 days after CA. The assessment of predictive effectiveness of this scoring model was conducted in both derivation and validation cohorts. RESULTS: Witnessed status, bystander cardiopulmonary resuscitation, initial rhythm, duration of resuscitation, Glasgow Coma Scale motor score, pupillary/corneal reflex, gray-white matter ratio and neuron-specific enolase exhibit strong correlations with the neurological outcomes in the derivation cohort (all p<0.05), and a risk scoring model for the prediction of an unfavorable outcome was created using these factors. In the validation cohort, significantly higher CANP scores were noted in the unfavorable outcome group. A CANP score ≥5 was associated with unfavorable neurological outcomes (sensitivity 68.8%, specificity 100%). CONCLUSION: The CANP score was established and validated for predicting the possible neurological prognosis in comatose post-CA survivors.

Case Report: A Novel Variant c.2262+3A>T of the SCN5A Gene Results in Intron Retention Associated With Incessant Ventricular Tachycardias.

Objective: Voltage-gated sodium channel Nav1.5 encoded by the SCN5A gene plays crucial roles in cardiac electrophysiology. Previous genetic studies have shown that mutations in SCN5A are associated with multiple inherited cardiac arrhythmias. Here, we investigated the molecular defect in a Chinese boy with clinical manifestations of arrhythmias. Methods: Gene variations were screened using whole-exome sequencing and validated by direct Sanger sequencing. A minigene assay and reverse transcription PCR (RT-PCR) were performed to confirm the effects of splice variants in vitro. Western blot analysis was carried out to determine whether the c.2262+3A>T variant produced a truncated protein. Results: By genetic analysis, we identified a novel splice variant c.2262+3A>T in SCN5A gene in a Chinese boy with incessant ventricular tachycardias (VT). This variant was predicted to activate a new cryptic splice donor site and was identified by in silico analysis. The variant retained 79 bp at the 5' end of intron 14 in the mature mRNA. Furthermore, the mutant transcript that created a premature stop codon at 818 amino acids [p.(R818*)] could be produced as a truncated protein. Conclusion: We verified the pathogenic effect of splicing variant c.2262+3A>T, which disturbed the normal mRNA splicing and caused a truncated protein, suggesting that splice variants play an important role in the molecular basis of early onset incessant ventricular tachycardias, and careful molecular profiling of these patients will be essential for future effective personalized treatment options.

Effect of arterial oxygen partial pressure inflection point on Venoarterial extracorporeal membrane oxygenation for emergency cardiac support.

BACKGROUND: Temporary circulatory support is a bridge between acute circulatory failure and definitive treatment or recovery. Currently, venoarterial extracorporeal membrane oxygenation (VA-ECMO) is considered to be one of the effective circulatory support methods, although cardiac function monitoring during the treatment still needs further investigation. Inflection point of arterial oxygen partial pressure (IPPaO2) may occur at an early stage in part of patients with a good prognosis after VA-ECMO treatment, and the relationship between time of IPPaO2 (tIPPaO2) and recovery of cardiac function or prognosis remains unclear. METHODS: To investigate this relationship, we retrospectively analyzed the clinical data of 71 patients with different conditions after treatment with VA-ECMO in the emergency center of Jiangsu Province Hospital between May 2015 and July 2020. Spearman's correlation analysis was used for the correlation between tIPPaO2 and quantitative data, and ROC curve for the predictive effect of tIPPaO2 on the 28-day mortality. RESULTS: Thirty-five patients were admitted because of refractory cardiogenic shock (26 of 35 survived) and the remaining 36 patients due to cardiac arrest (13 of 36 survived). The overall survival rate was 54.9% (39 of 71 survived). Acute physiology and chronic health evaluation II, ECMO time, tIPPaO2, continuous renal replacement therapy time, mechanical ventilation time, and bleeding complications in the survival group were lower than those in the non-survival group, with length of stay, intensive care unit stay, and platelet levels were being higher. The tIPPaO2 was negatively correlated with ejection fraction, and the shorter tIPPaO2 resulted in a higher 28-day survival probability, higher predictive value for acute myocardial infarction and fulminant myocarditis. CONCLUSIONS: Therefore, tIPPaO2 could be a reliable qualitative indicator of cardiac function in patients treated with VA-ECMO, which can reveal appropriate timing for adjusting VA-ECMO flow or weaning. TRIAL REGISTRATION: ChiCTR1900026105 .

Can Cardiopulmonary Rehabilitation Facilitate Weaning of Extracorporeal Membrane Oxygenation (CaRe-ECMO)? Study Protocol for a Prospective Multidisciplinary Randomized Controlled Trial.

Background: Mortality of patients suffering from critical illness has been dramatically improved with advanced technological development of extracorporeal membrane oxygenation (ECMO) therapy. However, the majority of ECMO-supported patients failed to wean from ECMO therapy. As one of several options, cardiopulmonary rehabilitation serves as effective intervention in the improvement of cardiovascular and respiratory function in various major critical illness. Nonetheless, its role in facilitating ECMO weaning has not yet been explored. The purpose of this study is to investigate the effectiveness of cardiopulmonary rehabilitation on rate of ready for ECMO weaning in ECMO-supported patients (CaRe-ECMO). Methods: The CaRe-ECMO trial is a randomized controlled, parallel group, clinical trial. This trial will be performed in a minimum number of 366 ECMO-supported eligible patients. Patients will be randomly assigned to either: (1) the CaRe-ECMO group, which will be treated with usual care including pharmacotherapy, non-pharmacotherapy, and specific nursing for ECMO therapy and the CaRe-ECMO program; or (2) the control group, which will receive usual care only. The CaRe-ECMO program consists of protocolized positioning, passive range of motion (PROM) training, neuromuscular electrical stimulation (NMES), surface electrical phrenic nerve stimulation (SEPNS), and pulmonary rehabilitation. The primary outcome of the CaRe-ECMO trial is the rate of ready for ECMO weaning at CaRe-ECMO day 7 (refers to 7 days after the CaRe-ECMO program initiation). Secondary outcomes include rate of ECMO and mechanical ventilation weaning, total length in day of ready for ECMO weaning, ECMO weaning and mechanical ventilation, all-cause mortality, rate of major post-ECMO complications, ECMO unit length of stay (LOS) and hospital LOS, total cost for hospitalization, cerebral performance category (CPC), activities of daily living (ADL), and health-related quality of life (HRQoL). Discussion: The CaRe-ECMO is designed to answer the question "whether cardiopulmonary rehabilitation can facilitate weaning of ECMO (CaRe-ECMO)." Should the implementation of the CaRe-ECMO program result in superior primary and secondary outcomes as compared to the controls, specifically the add-on effects of cardiopulmonary rehabilitation to the routine ECMO practice for facilitating successful weaning, the CaRe-ECMO trial will offer an innovative treatment option for ECMO-supported patients and meaningfully impact on the standard care in ECMO therapy. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT05035797.

Left Bundle Pacing for Left Bundle Branch Block and Intermittent Third-Degree Atrioventricular Block in a MYH7 Mutation-Related Hypertrophic Cardiomyopathy With Restrictive Phenotype in a Child.

Hypertrophic cardiomyopathy (HCM) is a group of myocardial diseases defined by cardiac hypertrophy which cannot be explained by secondary causes with a non-dilated left ventricle and preserved or increased ejection fraction. Sometimes it can be combined with restrictive cardiomyopathy. Here we describe a very rare case of a 12-year-old girl with non-obstructive hypertrophic cardiomyopathy accompanied by restrictive phenotype, complete left bundle branch block and intermittent third-degree atrioventricular block, who presented with recurrent syncope. Her father was also found to have hypertrophic cardiomyopathy and treated with implantable cardioverter defibrillator for ventricular tachycardia. Her younger brother is currently asymptomatic but echocardiogram showed hypertrophic cardiomyopathy. Genetic analysis identified a heterozygous missense mutation (c.2155C>T, p.R719W) of MYH7 in the proband girl, her father and her brother. The girl was treated with left bundle pacing and recovered well. The case we present further demonstrates the feasibility of left bundle pacing in children.