Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

Thrombolysis and extracorporeal cardiopulmonary resuscitation for cardiac arrest due to pulmonary embolism:A case report

BACKGROUND Cardiac arrest caused by acute pulmonary embolism(PE)is the most serious clinical circumstance,necessitating rapid identification,immediate cardiopulmonary resuscitation(CPR),and systemic thrombolytic therapy.Extracorporeal CPR(ECPR)is typically employed as a rescue therapy for selected patients when conventional CPR is failing in settings where it can be implemented.CASE SUMMARY We present a case of a 69-year-old male who experienced a prolonged cardiac arrest in an ambulance with pulseless electrical activity.Upon arrival at the emergency department with ongoing manual chest compressions,bedside pointof-care ultrasound revealed an enlarged right ventricle without contractility.Acute PE was suspected as the cause of cardiac arrest,and intravenous thrombolytic therapy with 50 mg tissue plasminogen activator was administered during mechanical chest compressions.Despite 31 minutes of CPR,return of spontaneous circulation was not achieved until 8 minutes after initiation of Veno-arterial extracorporeal membrane oxygenation(ECMO)support.Under ECMO support,the hemodynamic status and myocardial contractility significantly improved.However,the patient ultimately did not survive due to intracerebral hemorrhagic complications,leading to death a few days later in the hospital.CONCLUSION This case illustrates the potential of combining systemic thrombolysis with ECPR for refractory cardiac arrest caused by acute PE,but it also highlights the increased risk of significant bleeding complications,including fatal intracranial hemorrhage.

Approach to cardiac masses: Thinking inside and outside the box

In this editorial we comment on the article by Huffaker et al,published in the current issue of the World Journal of Clinical Cases.Cardiac masses encompass a broad range of lesions,potentially involving any cardiac structure,and they can be either neoplastic or non-neoplastic.Primitive cardiac tumors are rare,while metastases and pseudotumors are relatively common.Cardiac masses frequently pose significant diagnostic and therapeutic challenges.Multimodality imaging is fundamental for differential diagnosis,treatment,and surgical planning.In particular cardiac magnetic resonance(CMR)is currently the gold standard for noninvasive tissue characterization.CMR allows evaluation of the relationship between the tumor and adjacent structures,detection of the degree of infiltration or expansion of the mass,and prediction of the possible malignancy of a mass with a high accuracy.Different flow charts of diagnostic work-up have been proposed,based on clinical,laboratory and imaging findings,with the aim of helping physicians approach the problem in a pragmatic way(“thinking inside the box”).However,the clinical complexity of cancer patients,in particular those with rare syndromes,requires a multidisciplinary approach and an open mind to go beyond flow charts and diagnostic algorithms,in other words the ability to“think outside the box”.

Chinese clinical practice consensus for device-supported treatment in adults with post-cardiac arrest syndrome(2024 Edition)

During cardiac arrest (CA),severe ischemia and hypoxia occur in tissues and organs of the entire body,inflammatory cytokines are released,and ischemiareperfusion injury occurs after the return of spontaneous circulation (ROSC),leading to multiple organ dysfunction in the body;this condition is called post-CA syndrome(PCAS).^([1])According to the BASeline Investigation of Out-of-Hospital Cardiac Arrest (BASIC-OHCA) study,the crude incidence of emergency medical service (EMS)-assessed OHCA was 95.7 per 100,000 individuals,and only1.2%of those individuals survived to hospital discharge or30 d after being resuscitated by the EMS in China.

Association between echocardiography utilization and prognosis in patients with cardiac arrest

Despite efforts to develop treatment technology for cardiac arrest (CA),CA incidence and mortality rates are still high.^([1,2])A recent study of CA patients in emergency departments revealed that the incidence of CA is increasing annually,and the in-hospital survival rate of CA patients is only approximately 28.7%.^([3])Echocardiography has been widely used as an important monitoring tool in critical care and helps to identify the cause of shock,monitor hemodynamics,and guide fluid therapy utilization.^([4])One study reported that approximately one-third of patients underwent formal echocardiography during hospitalization in the intensive care unit (ICU).

Real-world cost-effectiveness of targeted temperature management in out-of-hospital cardiac arrest survivors: results from an academic medical center

BACKGROUND: Targeted temperature management(TTM) is a common therapeutic intervention, yet its cost-effectiveness remains uncertain. This study aimed to evaluate the real-world cost-effectiveness of TTM compared with that of conventional care in adult out-of-hospital cardiac arrest(OHCA) survivors using clinical patient-level data.METHODS: We conducted a retrospective cohort study at an academic medical center in the USA to assess the cost-effectiveness of TTM in adult non-traumatic OHCA survivors between 1 January, 2019 and 30 June, 2023. The primary outcome was survival to hospital discharge. Incremental cost-effectiveness ratios(ICERs) were calculated and compared with various decision makers' willingness to pay. Cost-effectiveness acceptability curves were utilized to evaluate the economic attractiveness of TTM. Uncertainty about the incremental cost and effect was explored with a 95% confidence ellipse.RESULTS: Among 925 non-traumatic OHCA survivors, only 30(3%) received TTM. After adjusting for potential confounders, the TTM group did not demonstrate a significantly lower cost(delta cost-$5,141, 95% confidence interval [95% CI]: $-35,347 to $25,065, P=0.79) and higher survival to hospital discharge(delta effect 6%, 95% CI:-11% to 23%, P=0.41). Additionally, a 95% confidence ellipse indicated uncertainty reflected by evidence that the true value of the ICER could be in any of the quadrants of the cost-effectiveness plane.CONCLUSION: Although TTM did not demonstrate a clear survival benefit in this study, its potential cost-effectiveness warrants further investigation with larger sample sizes. These findings highlight the need for additional research to optimize TTM use in OHCA care and inform resource allocation decisions.

Deep phenotyping of testosterone-prompted fibrosis in arrhythmogenic right ventricular cardiomyopathy using iPSC-derived engineered cardiac spheroids

Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the myocardium.While elevated testosterone levels have been implicated in the pathological process of ARVC,its exact contribution to cardiac fibrosis in ARVC remains unclear.In this study,we analyzed the potential contribution of gender-based differences on the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study,which was indicated by feature selection.Additionally,we established engineered cardiac spheroid models in vitro using patient-specific induced pluripotent stem cell(iPSC)-derived cardiomyocytes(iPSC-CMs)and iPSC-derived cardiac fibroblasts(icFBs).We elucidated the pathogenicity of abnormal splicing in the plakophilin-2(PKP2)gene caused by an intronic mutation.Additionally,pathogenic validation of the desmoglein-2(DSG2)point mutation further confirms the reliability of the models.Moreover,testosterone exacerbated the DNA damage in the mutated cardiomyocytes and further activated myofibroblasts in a chain reaction.In conclusion,we designed and constructed an in vitro three-dimensionally-engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.

Cardiac arrest, stony heart, and cardiopulmonary resuscitation: An updated revisit

The post-resuscitation period is recognized as the main predictor of cardiopul-monary resuscitation(CPR)outcomes.The first description of post-resuscitation syndrome and stony heart was published over 50 years ago.Major manifestations may include but are not limited to,persistent precipitating pathology,systemic ischemia/reperfusion response,post-cardiac arrest brain injury,and finally,post-cardiac arrest myocardial dysfunction(PAMD)after successful resuscitation.Why do some patients initially survive successful resuscitation,and others do not?Also,why does the myocardium response vary after resuscitation?These ques-tions have kept scientists busy for several decades since the first successful resuscitation was described.By modifying the conventional modalities of resu-scitation together with new promising agents,rescuers will be able to salvage the jeopardized post-resuscitation myocardium and prevent its progression to a dismal,stony heart.Community awareness and staff education are crucial for shortening the resuscitation time and improving short-and long-term outcomes.Awareness of these components before and early after the restoration of circulation will enhance the resuscitation outcomes.This review extensively addresses the underlying pathophysiology,management,and outcomes of post-resuscitation syndrome.The pattern,management,and outcome of PAMD and post-cardiac arrest shock are different based on many factors,including in-hospital cardiac arrest vs out-of-hospital cardiac arrest(OHCA),witnessed vs unwitnessed cardiac arrest,the underlying cause of arrest,the duration,and protocol used for CPR.Although restoring spontaneous circulation is a vital sign,it should not be the end of the game or lone primary outcome;it calls for better understanding and aggressive multi-disciplinary interventions and care.The development of stony heart post-CPR and OHCA remain the main challenges in emergency and critical care medicine.

Diagnostic Dilemma of Intracardiac Mass: Tumor versus Thrombus-Case Series and Systematic Review

Background: The differential diagnosis for intracavitary cardiac masses is limited, typically including vegetations, tumors, or thrombi. Cardiac thrombi can often mimic cardiac tumors on imaging, creating a diagnostic challenge. Primary cardiac tumors are rare and usually benign, whereas most cardiac tumors result from metastases, commonly originating from malignancies in the breast, lung, or melanoma. Aim: This report highlights the importance of distinguishing various cardiac masses based on clinical presentations, clinical courses, and radiological features. Case Presentation: We describe two cases of cardiac masses with unique and diverse clinical features. Each case posed significant diagnostic challenges due to their distinct presentations and clinical progressions. Conclusion: These cases underscore the importance of considering both benign and metastatic origins in the differential diagnosis of intracavitary cardiac masses. Accurate differentiation between thrombi and tumors is crucial for appropriate management and treatment.

Cardiac rehabilitation after cardiac surgery:An important underutilized treatment strategy

Physical inactivity remains in high levels after cardiac surgery,reaching up to 50%.Patients present a significant loss of functional capacity,with prominent muscle weakness after cardiac surgery due to anesthesia,surgical incision,duration of cardiopulmonary bypass,and mechanical ventilation that affects their quality of life.These complications,along with pulmonary complications after surgery,lead to extended intensive care unit(ICU)and hospital length of stay and significant mortality rates.Despite the well-known beneficial effects of cardiac rehabilitation,this treatment strategy still remains broadly underutilized in patients after cardiac surgery.Prehabilitation and ICU early mobilization have been both showed to be valid methods to improve exercise tolerance and muscle strength.Early mobilization should be adjusted to each patient’s functional capacity with progressive exercise training,from passive mobilization to more active range of motion and resistance exercises.Cardiopulmonary exercise testing remains the gold standard for exercise capacity assessment and optimal prescription of aerobic exercise intensity.During the last decade,recent advances in healthcare technology have changed cardiac rehabilitation perspectives,leading to the future of cardiac rehabilitation.By incorporating artificial intelligence,simulation,telemedicine and virtual cardiac rehabilitation,cardiac surgery patients may improve adherence and compliance,targeting to reduced hospital readmissions and decreased healthcare costs.

Effect of cardiac rehabilitation care after coronary intervention on cardiac function recovery and negative mood in patients with myocardial infarction

BACKGROUND Cardiovascular disease,particularly myocardial infarction(MI)profound impact on patients'quality of life and places a substantial burden on the healthcare and economy systems.Developments in medical technology have led to the emer-gence of coronary intervention as an essential method for treating MI.AIM To assess the effects of cardiac rehabilitation care on cardiac function recovery and negative emotions in MI after coronary intervention.METHODS This study included a total of 180 patients with MI during the period from June 2022 to July 2023.Selected patients were divided into two groups:An observation group,which receiving cardiac rehabilitation care;a control group,which re-ceiving conventional care.By comparing multiple observation indicators such as cardiac function indicators,blood pressure,exercise tolerance,occurrence of adverse cardiac events,and negative emotion scores between the two groups of patients.All the data were analyzed and compared between two groups.RESULTS There were 44 males and 46 females in the observation group with an average age of 36.26±9.88 yr;there were 43 males and 47 females in the control group,with an average age of 40.87±10.5 yr.After receiving the appropriate postoperative nursing measures,the results of the observation group showed significant improvement in several indicators compared with the control group.Indicators of cardiac function,such as left ventricular end-diastolic internal diameter and left ventricular ejection fraction were significantly better in the observation group than in the control group(P<0.05).Exercise endurance assessment showed that the 6-minute walking test distance was significantly increased in the patients of the observation group(P<0.01).In addition,the incidence of adverse cardiac events was significantly lower in the observation group,and negative mood scores were significantly reduced(P<0.05).CONCLUSION Cardiac rehabilitation care after coronary intervention has a significant positive impact on functional recovery.This emphasizes the importance of cardiac rehabilitation care to improve patient recovery.

Effects of systematic cardiac rehabilitation training in elderly patients with unstable angina following cardiac stent implantation

BACKGROUND Coronary stent implantation is usually used to treat unstable angina to alleviate stenosis or occlusion,promoting blood flow restoration and alleviating symptoms such as myocardial ischemia.And postoperative cardiac rehabilitation is essential for enhancing recovery and prognosis.Nevertheless,conventional rehabilitation lacks specificity,particularly for elderly patients with multiple comorbidities and poor compliance,rendering it less effective.AIM To investigate the effects of systematic cardiac rehabilitation training in elderly patients with unstable angina following coronary stenting intervention.METHODS A retrospective enrollment was conducted comprising fifty-four elderly patients with unstable angina pectoris who underwent systematic cardiac rehabilitation training after receiving coronary intervention as the rehabilitation group,while fifty-three elderly patients who received basic nursing and rehabilitation guidance measures after coronary intervention were assigned to the control group.Differences in Seattle Angina Questionnaire scores,survival quality(SF-36)scores,cardiopulmonary exercise function assessment index,echocardiographic cardiac function index,and adverse cardiovascular events were compared between the two groups.RESULTS After intervention,the rehabilitation group observed greater VO2 Max,maximum metabolic equivalent,eft ventricular ejection fraction,left ventricular end-diastolic diameter and smaller left ventricular end-systolic diameter.And the rehabilitation group observed greater scores of physical activity limitation,stable angina pectoris,treatment satisfaction,and SF-36 score.The incidence of adverse cardiovascular events in the two groups,showed no significant difference.CONCLUSION Systematic cardiac rehabilitation following coronary stenting in elderly patients with unstable angina pectoris can enhance cardiac function recovery,consequently enhancing both quality of life and cardiopulmonary exercise tolerance.

Overall approaches to cardiac tumors:Still an unsolved enigma?

Cardiac tumors are neoplasms involving heart structures at any level,meaning the myocardium,valves,and cardiac chambers.When considering cardiac masses,it is not uncommon for surgeons to be surprised when they diagnose one.The real incidence of this complex group of diseases has been explored only after cardiac diagnostic tools became more appropriate.Despite differential diagnosis being relevant,surgical indication is usually requested for all malignant cardiac tumors and also for many types of benign tumors.The development of cardiac imaging techniques,therefore,has been the key point for a better understanding of the history of cardiac tumors and especially of the relevance of surgical indication in such conditions.Systematic and combined applications of echocardiography,cardiac computed tomography and magnetic resonance allow in the majority of case a clear definition of the nature of a newly discovered cardiac mass.The presence of a Li-Fraumeni syndrome seems to be the trigger aspect in accelerating the propensity of developing a cardiac tumor.Despite the revolutionary usefulness of the cardiac imaging techniques available,it is still considered a hazard to diagnose a malignant cardiac mass just with radiological imaging;the mainstay of the final diagnosis stands in surgical excision of the mass and histopathological report.

Quality of life and functional capacity in patients after cardiac surgery intensive care unit

Coronary heart disease and aortic stenosis are prevalent cardiovascular diseases worldwide,leading to morbidity and mortality.Coronary artery bypass grafting(CABG)and surgical aortic valve replacement(SAVR)have therapeutic benefits,including improved postoperative quality of life(QoL)and enhanced patient functional capacity which are key indicators of cardiac surgery outcome.In this article,we review the latest studies of QoL outcomes and functional capacity in patients who underwent cardiac surgery.Many standardized instruments are used to evaluate QoL and functional conditions.Preoperative health status,age,length of intensive care unit stay,operative risk,type of procedure,and other pre-,intra-,and postoperative factors affect postoperative QoL.Elderly patients experience impaired physical status soon after cardiac surgery,but it improves in the following period.CABG and SAVR are associated with increases of physical and mental health and functional capacity in the immediate postoperative and the long long-term.Cardiac rehabilitation improves patient functional capacity,QoL,and frailty following cardiac surgery.

Progress in the Early Mobilization of Patients after Cardiac Intervention

Early activity has a positive effect on the rehabilitation process of patients after cardiac intervention. This paper summarizes the concept and significance of early activity after cardiac intervention, the best time and mode of different types of early activity after cardiac intervention, and the factors affecting early activity, aiming to provide a basis for clinical medical staff to provide safe and effective guidance of early activity after cardiac intervention.

The association between C-reactive protein to albumin ratio and 6-month neurological outcome in patients with in-hospital cardiac arrest

The global incidence rates of in-hospital cardiac arrest(IHCA)range from1.2 to 9.0 per1,000 hospitalized patients,as per the National Cardiac Arrest Database.[1] While IHCAs tend to exhibit superior 30-day survival rates relative to out-of-hospital cardiac arrests (OHCA) due to situational advantages,such as immediate access to medical personnel and treatments.

Safety and effectiveness of neuromuscular electrical stimulation in cardiac surgery:A systematic review

BACKGROUND Lack of mobilization and prolonged stay in the intensive care unit(ICU)are major factors resulting in the development of ICU-acquired muscle weakness(ICUAW).ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery,and may be a risk factor for prolonged duration of mechanical ventilation,associated with a higher risk of readmission and higher mortality.Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay.Neuromuscular electrical stimulation(NMES)is an alternative modality of exercise in patients with muscle weakness.A major advantage of NMES is that it can be applied even in sedated patients in the ICU,a fact that might enhance early mobilization in these patients.AIM To evaluate safety,feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery.METHODS We performed a search on Pubmed,Physiotherapy Evidence Database(PEDro),Embase and CINAHL databases,selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials(RCTs)that included implementation of NMES in patients before after cardiac surgery.RCTs were assessed for methodological rigor and risk of bias via the PEDro.The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function.RESULTS Ten studies were included in our systematic review,resulting in 703 participants.Almost half of them performed NMES and the other half were included in the control group,treated with usual care.Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery.Functional capacity was assessed in 8 studies via 6MWT or other indices,and improved only in 1 study before and in 1 after cardiac surgery.Nine studies explored the effects of NMES on muscle strength and function and,most of them,found increase of muscle strength and improvement in muscle function after NMES.NMES was safe in all studies without any significant complication.CONCLUSION NMES is safe,feasible and has beneficial effects on muscle strength and function in patients after cardiac surgery,but has no significant effect on functional capacity.

Left bundle branch pacing set to outshine biventricular pacing for cardiac resynchronization therapy?

The deleterious effects of long-term right ventricular pacing necessitated the search for alternative pacing sites which could prevent or alleviate pacinginduced cardiomyopathy.Until recently,biventricular pacing(BiVP)was the only modality which could mitigate or prevent pacing induced dysfunction.Further,BiVP could resynchronize the baseline electromechanical dssynchrony in heart failure and improve outcomes.However,the high non-response rate of around 20%-30%remains a major limitation.This non-response has been largely attributable to the direct non-physiological stimulation of the left ventricular myocardium bypassing the conduction system.To overcome this limitation,the concept of conduction system pacing(CSP)came up.Despite initial success of the first CSP via His bundle pacing(HBP),certain drawbacks including lead instability and dislodgements,steep learning curve and rapid battery depletion on many occasions prevented its widespread use for cardiac resynchronization therapy(CRT).Subsequently,CSP via left bundle branch-area pacing(LBBP)was developed in 2018,which over the last few years has shown efficacy comparable to BiVP-CRT in small observational studies.Further,its safety has also been well established and is largely free of the pitfalls of the HBP-CRT.In the recent metanalysis by Yasmin et al,comprising of 6 studies with 389 participants,LBBPCRT was superior to BiVP-CRT in terms of QRS duration,left ventricular ejection fraction,cardiac chamber dimensions,lead thresholds,and functional status amongst heart failure patients with left bundle branch block.However,there are important limitations of the study including the small overall numbers,inclusion of only a single small randomized controlled trial(RCT)and a small follow-up duration.Further,the entire study population analyzed was from China which makes generalizability a concern.Despite the concerns,the meta-analysis adds to the growing body of evidence demonstrating the efficacy of LBBP-CRT.At this stage,one must acknowledge that the fact that still our opinions on this technique are largely based on observational data and there is a dire need for larger RCTs to ascertain the position of LBBPCRT in management of heart failure patients with left bundle branch block.

Total suprarenal aortic occlusion with cardiac disease: a case series of three cases

Acute aortic occlusion(AAO)has been very rarely reported in the literature and is a potentially life-threatening emergency.[1-5]AAO mostly occurs in cardiac disease patients,[1-4,6,7]and leads to cardiac complications.[1,2,5,6]Suprarenal aortic occlusion(SAO)is a very rare type of AAO,and infrarenal aortic occlusion(IAO)accounts for 75.8%-97.8%.[1,3,5-7]SAO is different from IAO in some clinical manifestations,treatment strategies,and prognoses.[3,6-8]SAO with cardiac disease will make the condition more complex and could easily cause a delay in diagnosis and portend worse outcomes with amputation and mortality rates.[1,3,6]Early and fast diagnosis and positive revascularization treatment are necessary to prevent cases from becoming fatal.[1-3]Herein,we present a case series of SAO with cardiac disease.

A contradictory phenomenon of thicken pericardium and cardiac compression without inferior vena cava dilation:sign of IVC escape

A 77-year-old female presented with shortness of breath and tightness of chest was admitted.Her past medical history included hypertension and she has been taking nifedipine regularly.Two years before,she was diagnosed with pericardial effusion(Figure 1)and had pericardiocentesis drainage.On physical examination,her blood pressure was 151/100 mm-Hg and her pulse rate was 91 beats/min.