Agregador de feeds

Trials. 2022 Dec 9;23(1):988. doi: 10.1186/s13063-022-06931-4.

ABSTRACT

BACKGROUND: Coronary artery disease (CAD) remains a severe socio-economic burden in the Western world. Coronary obstruction and subsequent myocardial ischemia result in the progressive replacement of contractile myocardium with dysfunctional, fibrotic scar tissue. Post-infarctional remodelling is causal for the concomitant decline of left-ventricular function and the fatal syndrome of heart failure. Available neurohumoral treatment strategies aim at the improvement of symptoms. Despite extensive research, therapeutic options for myocardial regeneration, including (stem)-cell therapy, gene therapy, cellular reprogramming or tissue engineering, remain purely experimental. Thus, there is an urgent clinical need for novel treatment options for inducing myocardial regeneration and improving left-ventricular function in ischemic cardiomyopathy. Shockwave therapy (SWT) is a well-established regenerative tool that is effective for the treatment of chronic tendonitis, long-bone non-union and wound-healing disorders. In preclinical trials, SWT regenerated ischemic myocardium via the induction of angiogenesis and the reduction of fibrotic scar tissue, resulting in improved left-ventricular function.

METHODS: In this prospective, randomized controlled, single-blind, monocentric study, 80 patients with reduced left-ventricular ejection fraction (LVEF≤ 40%) are subjected to coronary-artery bypass-graft surgery (CABG) surgery and randomized in a 1:1 ratio to receive additional cardiac SWT (intervention group; 40 patients) or CABG surgery with sham treatment (control group; 40 patients). This study aims to evaluate (1) the safety and (2) the efficacy of cardiac SWT as adjunctive treatment during CABG surgery for the regeneration of ischemic myocardium. The primary endpoints of the study represent (1) major cardiac events and (2) changes in left-ventricular function 12 months after treatment. Secondary endpoints include 6-min walk test distance, improvement of symptoms and assessment of quality of life.

DISCUSSION: This study aims to investigate the safety and efficacy of cardiac SWT during CABG surgery for myocardial regeneration. The induction of angiogenesis, decrease of fibrotic scar tissue formation and, thus, improvement of left-ventricular function could lead to improved quality of life and prognosis for patients with ischemic heart failure. Thus, it could become the first clinically available treatment strategy for the regeneration of ischemic myocardium alleviating the socio-economic burden of heart failure.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03859466. Registered on 1 March 2019.

PMID:36494706 | PMC:PMC9733047 | DOI:10.1186/s13063-022-06931-4

Sci Rep. 2022 Dec 9;12(1):21362. doi: 10.1038/s41598-022-21721-3.

ABSTRACT

Oncotherapeutics research is progressing at a rapid pace, however, not many drugs complete the successful clinical trial because of severe off-target toxicity to cardiomyocytes which ultimately leads to cardiac dysfunction. It is thus important to emphasize the need for early testing for possible cardiotoxicity of emerging oncotherapeutics. In this study, we assessed a novel stem cell-derived cardiac model for testing for cardiotoxicity of novel oncotherapeutics. We evaluated the cardiotoxic effect of synthesized derivatives of oncotherapeutics, quercetin (QMJ-2, -5, and -6) and cinnamic acid (NMJ-1, -2, and -3) using human Wharton's jelly mesenchymal stem cells-derived cardiomyocytes (WJCM) against known cardiotoxic oncologic drugs, doxorubicin, 5-fluorouracil, cisplatin. QMJ-6, NMJ-2, and NMJ-3 were not cardiotoxic and had minimum cardiac side effects. They did not show any effect on cardiomyocyte viability, caused low LDH release, and intracellular ROS production kept the calcium flux minimal and protected the active mitochondrial status in cardiomyocytes. They persevered cardiac-specific gene expression as well. However, compounds QMJ-2, QMJ-5, and NMJ-1 were cardiotoxic and the concentration needs to be reduced to prevent toxic effects on cardiomyocytes. Significantly, we were able to demonstrate that WJCM is an efficient cardiac testing model to analyze the cardiotoxicity of drugs in a human context.

PMID:36494370 | PMC:PMC9734143 | DOI:10.1038/s41598-022-21721-3

J Mol Cell Cardiol. 2022 Dec 6;175:29-43. doi: 10.1016/j.yjmcc.2022.11.006. Online ahead of print.

ABSTRACT

Regenerating the injured heart remains one of the most vexing challenges in cardiovascular medicine. Cell therapy has shown potential for treatment of myocardial infarction, but low cell retention so far has limited its success. Here we show that intramyocardial injection of highly apoptosis-resistant unrestricted somatic stem cells (USSC) into infarcted rat hearts resulted in an unprecedented thickening of the left ventricular wall with cTnT+/BrdU+ cardiomyocytes that was paralleled by progressively restored ejection fraction. USSC induced significant T-cell enrichment in ischemic tissue with enhanced expression of T-cell related cytokines. Inhibition of T-cell activation by anti-CD28 monoclonal antibody, fully abolished the regenerative response which was restored by adoptive T-cell transfer. Secretome analysis of USSC and lineage tracing studies suggest that USSC secrete paracrine factors over an extended period of time which boosts a T-cell driven endogenous regenerative response mainly from adult cardiomyocytes.

PMID:36493853 | DOI:10.1016/j.yjmcc.2022.11.006

Altern Lab Anim. 2022 Dec 9:2611929221143774. doi: 10.1177/02611929221143774. Online ahead of print.

ABSTRACT

Stem cell-based therapy presents an attractive alternative to conventional therapies for degenerative diseases. Numerous studies have investigated the capability of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) to contribute to the regeneration of cardiomyocytes, and the results have encouraged further basic and clinical studies on the MSC-based treatment of cardiomyopathies. This study aimed to determine the potential of cardiomyogenic transcription factors in differentiating hUC-MSCs into cardiac-like cells in vitro. MSCs were isolated from umbilical cord tissue and were transduced with the transcription factor genes, GATA-4 and Nkx 2.5, via infection with lentiviruses, to promote differentiation into the cardiomyogenic lineage. Gene and protein expression were analysed with qPCR and immunocytochemical staining. After transduction, differentiated cardiac-like cells showed significant expression of cardiac genes and proteins, namely GATA-4, Nkx-2.5, cardiac troponin I (cTnI) and myosin heavy chain (MHC). The cardiomyogenic-induced group significantly overexpressed cardiac-specific genes (GATA-4, Nkx-2.5, cTnI, MHC, α-actinin and Wnt2). Expression of the calcium channel gene was also significantly increased, while the sodium channel gene was downregulated in the transduced hUC-MSCs, as compared to non-transduced cells. The results suggest that GATA-4 and Nkx-2.5 interact synergistically in the activation of downstream cardiac transcription factors, demonstrating the functional convergence of hUC-MSC differentiation into cardiac-like cells. These findings could potentially be utilised in the efficient production of cardiac-like cells from stem cells; these cardiac-like cells could then be used in various applications, such as for in vivo implantation in infarcted myocardium, and for drug screening in toxicity testing.

PMID:36484201 | DOI:10.1177/02611929221143774

Medicine (Baltimore). 2022 Dec 2;101(48):e31953. doi: 10.1097/MD.0000000000031953.

ABSTRACT

With the aging of the population, the incidence of senile degenerative valvular heart disease is expected to increase. Transcatheter aortic valve replacement (TAVR) has been used for patients at lower surgical risk with symptomatic severe aortic valve stenosis. Because of the improvements in TAVR technology and increasing experience of the operators, TAVR is regarded as a safe and feasible procedure. Bleeding events during the TAVR perioperative period, especially gastrointestinal (GI) bleeding, have been proven to be related to the long-term prognosis and mortality. Elderly patients with valvular heart disease are susceptible to GI bleeding because of their use of antithrombotic drugs, physical damage of coagulation factors, and GI angiodysplasia. Frequent GI bleeding and low levels of preoperative hemoglobin increase the risk of TAVR, especially for elderly patients. Because of these risks, which are easily overlooked, we should focus more attention on the perioperative management of TAVR. Reasonable screening tools, including blood examinations, risk evaluation scales, and endoscopy, are beneficial to the prevention of complications that can occur during the perioperative period. Additionally, medical therapy can safely help patients at high-risk for bleeding patients throughout the perioperative period. This study aimed to characterize the pathology of TAVR patients and discuss treatment strategies for GI bleeding during the perioperative period.

PMID:36482568 | PMC:PMC9726417 | DOI:10.1097/MD.0000000000031953

Perfusion. 2022 Dec 8:2676591221145623. doi: 10.1177/02676591221145623. Online ahead of print.

ABSTRACT

INTRODUCTION: Bloodless cardiac surgery refers to open-heart surgery without blood or blood products. The cardiopulmonary bypass (CPB) circuits are primed with crystalloid solely, and there is no intraoperative blood transfusion.

METHODS: Our program considers bloodless congenital cardiac surgery with a minimal invasive extracorporeal circulation (MiECC) system for patients above 10 kg of weight. We performed a single-center retrospective cohort study of all consecutive patients undergoing bloodless cardiac surgery for congenital heart defects between January 2016 and December 2018.

RESULTS: A total of 164 patients were reviewed (86 male and 78 female) at a median age of 9.6 years (interquartile range (IQR), 4.5-15), a weight of 32 kg (IQR, 16-55), preoperative hemoglobin 13.7 g/dl (IQR, 12.6-14.9), and preoperative hematocrit of 40.4% (IQR, 37.2-44.3). Median CPB time was 81.5 min (IQR, 58-125), and median hematocrit coming off CPB was 26% (IQR, 23-29.7). The congenital heart surgery risk (STAT) category was distributed in STAT 1 for 70, STAT 2 for 80, STAT 3 for 9, and STAT 4 for 5 patients. Most patients (95%) were extubated in the operating room with a low complication rate during the hospital stay (14.6%). Only 6 (4%) patients needed a blood transfusion during the postoperative period, with a higher incidence of complications during the hospital course (p < 0.001).

CONCLUSIONS: Bloodless congenital heart surgery with MiECC system is safe in low-surgical-risk patients. Our patients had a low rate of complications and short hospital stays.

PMID:36482703 | DOI:10.1177/02676591221145623

Semin Thorac Cardiovasc Surg. 2022 Dec 6:S1043-0679(22)00275-1. doi: 10.1053/j.semtcvs.2022.11.008. Online ahead of print.

ABSTRACT

Repair of concomitant aortic and mitral valvular disease with involvement of the aortomitral curtain requires a technically complex operation colloquially termed the commando procedure. Surgical outcomes of this procedure are not well described. The objective of this study was to examine outcomes of the commando procedure at our center. We identified all patients undergoing concomitant aortic and mitral valve replacements from 2004-2021. Of 363 patients, 41 underwent reconstruction of the aortomitral curtain. Survival analysis and multivariable modeling were used to examine outcomes and risk factors for mortality. The median age was 52 (IQR 44-71) years. Preoperatively, 4 of 41 (9.8%) patients had renal failure, and 10 of 41 (24.4%) had a stroke. The most common surgical indication was endocarditis in 25 of 41 (61.0%) patients. 25 of 41 (61.0%) patients underwent redo sternotomy, and 23 of 41 (56.1%) had previous prosthetic valves. Operative mortality was 14 of 41 (34.1%), and 8 of 41 (9.5%) patients received a permanent pacemaker. Survival at 1, 3, and 5 years was 55.4% (95% confidence interval (CI), 40.6-75.5%), 50.3% (35.0-72.3%), and 37.7% (19.3-73.9%) respectively. Cox proportional hazards regression identified previous sternotomy (HR 4.76, 95% CI 1.21-18.73), and female gender (HR 1.39, 95% CI 1.17-13.82) as risk factors for mortality. Patients undergoing reconstruction of the aortomitral curtain represent a high-risk population with complex surgical indications. Due to high perioperative morbidity and mortality, this procedure should be performed only when necessary. Despite a high up front morbidity burden, outcomes remain favorable for patients who survive the initial hospitalization.

PMID:36481412 | DOI:10.1053/j.semtcvs.2022.11.008

JAMA Cardiol. 2022 Dec 7. doi: 10.1001/jamacardio.2022.4457. Online ahead of print.

ABSTRACT

IMPORTANCE: Racial and ethnic minority and socioeconomically disadvantaged patients have been underrepresented in randomized clinical trials. Efforts have focused on enhancing inclusion of minority groups at sites participating at clinical trials; however, there may be differences in the patient populations of the sites that participate in clinical trials.

OBJECTIVE: To identify any differences in the racial, ethnic, and socioeconomic composition of patient populations among candidate sites in the US that did vs did not participate in trials for novel transcatheter therapies.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used Medicare Provider Claims from 2019 for patients admitted to hospitals in the US. All clinical trials for transcatheter mitral and tricuspid valve therapies and the hospitals participating in each of the trials were identified using ClinicalTrials.gov. Hospitals with active cardiac surgical programs that did not participate in the trials were also identified. Data analysis was performed between July 2021 and July 2022.

EXPOSURES: Multivariable linear regression models were used to identify differences in racial, ethnic, and socioeconomic characteristics among patients undergoing cardiac surgery or transcatheter aortic valve replacement at trial vs nontrial hospitals.

MAIN OUTCOME AND MEASURES: The main outcome of the study was participation in a clinical trial for novel transcatheter mitral or tricuspid valve therapies.

RESULTS: A total of 1050 hospitals with cardiac surgery programs were identified, of which 121 (11.5%) participated in trials for transcatheter mitral or tricuspid therapies. Patients treated in trial hospitals had a higher median zip code-based household income (difference of $5261; 95% CI, $2986-$7537), a lower Distressed Communities Index score (difference of 5.37; 95% CI, 2.59-8.15), and no significant difference in the proportion of patients dual eligible for Medicaid (difference of 0.86; 95% CI, -2.38 to 0.66). After adjusting for each of the socioeconomic indicators separately, there was less than 1% difference in the proportion of Black and Hispanic patients cared for at hospitals participating vs not participating in clinical trials.

CONCLUSIONS AND RELEVANCE: In this cohort study among candidate hospitals for clinical trials for transcatheter mitral or tricuspid valve therapies, trial hospitals took care of a more socioeconomically advantaged population than nontrial hospitals, with a similar proportion of Black and Hispanic patients. These data suggest that site selection efforts may improve enrollment of socioeconomically disadvantaged patients but may not improve the enrollment of Black and Hispanic patients.

PMID:36477493 | DOI:10.1001/jamacardio.2022.4457

Trials. 2022 Dec 7;23(1):984. doi: 10.1186/s13063-022-06965-8.

ABSTRACT

BACKGROUND: Valvular heart disease remains common in both developed and developing countries, and it requires timely surgical treatment when necessary. However, the stability of hemodynamics during anesthesia induction in patients undergoing valve replacement surgery is difficult to maintain due to their impaired cardiac function. Remimazolam, a novel and ultrashort-acting intravenous sedative-hypnotic, may be beneficial to stable hemodynamics, but the evidence is limited. Therefore, this study aims to evaluate the effect of remimazolam induction on hemodynamics compared with midazolam and etomidate in patients undergoing valve replacement surgery.

METHODS: This is a prospective, multicenter randomized controlled trial (RCT). Three hundred and sixty-three non-obese adult patients aged 45 to 80 years old undergoing valve surgery with cardiopulmonary bypass will be randomly allocated to receive remimazolam tosilate, midazolam, or etomidate during anesthetic induction. The primary outcome is the incidence of hypotension within 20 min after the administration of investigated drugs. The hypotension is defined as systolic blood pressure (SBP) < 90 mmHg or a 30% reduction in SBP from baseline or the application of vasoactive drugs. Secondary outcomes include incidence of successful sedation, time to successful sedation, incidence of delirium and postoperative low cardiac output syndrome within 7 days after surgery, hospital mortality, mechanical ventilation time, ICU length of stay, and hospital length of stay.

DISCUSSION: To our knowledge, this is the first prospective RCT to investigate the efficacy and safety of remimazolam induction in adult cardiac surgery compared with midazolam and etomidate. This study will provide important information on the application of remimazolam in cardiac surgery in the future.

TRIAL REGISTRATION: Chinese Clinical Trial Registry chictr.org.cn ChiCTR2100050122. Registered on August 16, 2021.

PMID:36476322 | PMC:PMC9727858 | DOI:10.1186/s13063-022-06965-8

Circ J. 2022 Dec 6. doi: 10.1253/circj.CJ-22-0443. Online ahead of print.

ABSTRACT

BACKGROUND: We compared postoperative outcomes in octogenarians who underwent off-pump isolated coronary artery bypass grafting for multivessel disease using either skeletonized bilateral or single internal thoracic artery (ITA).Methods and Results: Among 1,532 patients who underwent isolated coronary artery bypass grafting between 2002 and 2021, 173 octogenarians were analyzed retrospectively. After inverse probability of treatment weighting, we found no statistically significant difference regarding patients' preoperative characteristics. No patient experienced deep sternal wound infection. More patients in the single than bilateral ITA group died within 30 days after surgery (5.0% vs. 0%, respectively; P=0.003). The mean follow-up duration was 4.2 years. At 5 years, the freedom from overall death following bilateral versus single ITA grafting was 78.2% and 53.7%, respectively (log-rank test, P=0.003), and freedom from major adverse cardiac and cerebrovascular events (MACCE) was 67.9% and 44.8% respectively (log-rank test, P=0.002). In multivariable Cox models, bilateral ITA grafting was significantly associated with a lower risk of overall death (hazard ratio [HR] 0.555; 95% confidence interval [CI] 0.342-0.903; P=0.018) and MACCE (HR 0.586; 95% CI 0.376-0.913; P=0.018).

CONCLUSIONS: Compared with single ITA grafting, off-pump skeletonized bilateral ITA grafting is associated with lower rates of overall death and MACCE in octogenarians undergoing CABG and does not increase the risk of deep sternal wound infection.

PMID:36476828 | DOI:10.1253/circj.CJ-22-0443

Cureus. 2022 Nov 5;14(11):e31133. doi: 10.7759/cureus.31133. eCollection 2022 Nov.

ABSTRACT

Women with native heart valve disease who are considering getting pregnant should have a complete risk estimation to determine whether an intervention is required prior to becoming pregnant and, if so, to determine when it should be performed and what kind of surgical therapy will be used. Pregnancy is linked to early and late structural valve degeneration in women who have bioprostheses, suggesting a high reoperation rate. A mechanical valve during pregnancy increases the risk of maternal complications such as valve thrombosis and mortality. The claim that women with defective hearts should not become pregnant was driven by the high maternal death rate among cardiac patients who became pregnant. A preoperative anticoagulation therapy trial helped women scheduled for valve replacement to acquire complete information as to the choice of the prosthetic device. Integrated risk stratification scheme for pregnant patients with valvular heart disease, with WHO classification and an algorithmic approach to both preconception counseling and anticoagulation strategy as outlined here, as well as early referral to a cardiologist with expertise in the management of cardiac disease and pregnancy for these complex patients is recommended. However, in reality, some women present while pregnant and valve disease needs to be managed, balancing maternal outcome and fetal risk. In general, optimizing the hemodynamic situation of the mother is also beneficial to the fetus. However, cardiac surgery carries a high risk for the fetus. No anticoagulant regimen can be said to be entirely safe for use during pregnancy, as there is a degree of risk with each regimen. Therefore, this review has been done to find appropriate management for women dealing with such conditions.

PMID:36475179 | PMC:PMC9720036 | DOI:10.7759/cureus.31133

Radiol Case Rep. 2022 Dec 1;18(2):651-656. doi: 10.1016/j.radcr.2022.11.005. eCollection 2023 Feb.

ABSTRACT

Thrombotic events in SARS-COV-2 disease patients are frequent, especially in patients with comorbidities such as heart failure, hypertension, cancer, diabetes mellitus, kidney failure, vascular disease, and other pulmonary illnesses. In severe cases, in particular those of hospitalized patients with other comorbidities, the development of thrombotic events in spite of anticoagulation therapy has been observed. The main thrombotic events are pulmonary thromboembolism, cerebral ischemic stroke, and peripheral artery thrombosis. Despite the severity of SARS-COV-2 disease, some patients with the aforementioned comorbidities develop thrombotic events regardless of the severity of their SARS-COV-2 infection. In this setting, the cerebellum makes no exception as an uncommon, but still possible target for thrombotic events.

PMID:36474520 | PMC:PMC9714958 | DOI:10.1016/j.radcr.2022.11.005

World J Pediatr Surg. 2022 Mar 1;5(2):e000328. doi: 10.1136/wjps-2021-000328. eCollection 2022.

ABSTRACT

BACKGROUND: The noise in an operating room may have a detrimental effect on human cognitive functions, and it may cause perioperative anxiety with prolonged exposure. The aim of this study was to investigate the effects of music therapy and use of earplugs and normal noise level in the operating room under general anesthesia of pediatric patients on hemodynamic parameters and postoperative emergence delirium.

METHODS: One hundred and five pediatric patients were involved in this study. The patients were randomly divided into three groups. Group N was exposed to the ambient operating room noise, group S received earplugs from an independent anesthesiologist, and group M used a CD player. The preoperative anxiety levels of children were evaluated with the Modified Yale Preoperative Anxiety Scale (M-YPAS). Mean arterial pressure (MAP) and heart rate were recorded at 30-minute periods until the completion of surgery, end of surgery and postoperatively. During each measurement, noise level recordings were performed using sonometer. Pediatric Anesthesia Emergency Delirium (PAED) score was evaluated after postoperative extubation.

RESULTS: M-YPAS was similar between groups. The MAP at 30 and 60 min intraoperatively, at end of surgery, and at 5, 10, and 15 min postoperatively was significantly lower in group S than in group N. There were no differences in heart rate among the groups. Postoperative PAED score was not significantly different among the groups.

CONCLUSIONS: The music therapy was not more effective than silence and operating noise room in reducing PAED score postoperatively in pediatric patients.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03544502).

PMID:36474510 | PMC:PMC9717318 | DOI:10.1136/wjps-2021-000328

BMC Cardiovasc Disord. 2022 Dec 6;22(1):527. doi: 10.1186/s12872-022-02955-5.

ABSTRACT

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) is commonly used in adult aortic surgery and pediatric complex congenital heart disease, and is associated with pathophysiological changes and postoperative complications. Here, a temperature-controlled circulatory arrest model in rats was established to study the suitable temperature of circulatory arrest by investigating the damage to body organs under different temperatures.

METHODS: Thirty Sprague‒Dawley rats were randomly divided into 5 equal groups for DHCA experiments: I (15-20 °C), II (20-25 °C), III (25-30 °C), IV (normothermic cardiopulmonary bypass), and V (sham operation group). Blood gas analysis, homodynamic parameters, and intervals of cardiac recovery were measured at different time points in all groups. Morphological changes in intestinal tissue were observed under light and electron microscopes. Oxidative stress was measured by MPO activity, MDA, and SOD content. Tissue damage was confirmed by serum detection of ALT, AST, BUN, Cr, and LDH. To examine the inflammatory response, cytokines, including IL-1, IL-4, IL-10, IFN-γ, and TNF-α, were detected.

RESULTS: The extracorporeal circulation technique caused damage to the body; the degree of the damage caused by the circulatory arrest technique may be related to circulating temperature, with the least amount of damage occurring at 20-25 °C compared to 15-20 °C and 25-30 °C. Ischemia and hypoxia can cause intestinal tissue damage, which manifests primarily as a loss of the intestinal mucosal barrier. Ischemic intestinal damage caused by DHCA was not associated with inflammation.

CONCLUSION: The study provides new insights into the pathophysiologic mechanisms of DHCA.

PMID:36474159 | PMC:PMC9724398 | DOI:10.1186/s12872-022-02955-5

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2022 Oct;34(10):1031-1035. doi: 10.3760/cma.j.cn121430-20220520-00499.

ABSTRACT

OBJECTIVE: To investigate the effect of extracorporeal membrane oxygenation (ECMO) on in-hospital survival and prognosis of adult patients with fulminant myocarditis.

METHODS: The registration materials of 21 patients with fulminant myocarditis supported by veno-arterial ECMO (VA-ECMO) from March 2019 to January 2022 in the Heart Center of the First Hospital of Lanzhou University were selected from the Chinese Society for Extracorporeal Life Support (CSECLS) Registry Database. The clinical baseline data, laboratory and echocardiographic data, VA-ECMO related parameters, complications and in-hospital outcome were recorded. The main end events of follow-up were death and readmission due to heart failure.

RESULTS: (1) The median age of 21 patients was (42.7±16.4) years, there were 12 males (57.1%) and 9 females (42.9%), and 16 patients (76.2%) survived in hospital and 5 patients (23.8%) died in hospital. (2) Compared with the survival group, patients in the death group had a higher proportion of invasive ventilator support and continuous renal replacement therapy (CRRT) [3/16 (18.8%) vs. 4/5 (80.0%), 3/16 (18.8%) vs. 4/5 (80.0%)], and a lower survival after VA-ECMO score (SAVE) [score: -5.0 (-5.0, -3.0) vs. 1.0 (-6.0, 5.0)], the serum creatinine (SCr) level was higher during VA-ECMO support [μmol/L: 248.0 (144.0, 447.0) vs. 83.0 (71.7, 110.9)], the platelet count (PLT) level was lower [×109/L: 60.0 (31.5, 96.5) vs. 100.0 (71.0, 139.3)], and the ECMO initial support flow rate was higher (L/min: 3.2±0.7 vs. 2.6±0.4). All the differences were statistically significant (all P < 0.05). (3) The echocardiography indexes of the survival group were significantly improved at discharge compared with those at admission [left ventricular ejection fraction (LVEF, %): 54.0±6.7 vs. 30.0±7.2], left ventricular end-diastolic volume [(LVESV, mL): 55.7±27.5 vs. 85.9±28.7], cardiac index [(CI, L×min-1×m-2): 2.6±0.4 vs. 1.9±0.6], cardiac output [(CO, L/min): 4.5±0.7 vs. 3.2±0.9]. All the differences were statistically significant (all P < 0.05). (4) The median follow-up time of the 16 survivial patients was 9 (2, 14) months. During the follow-up period, 5 patients (31.3%) were readmitted to the hospital due to heart failure (1 case of cardiogenic death). The average ECMO support duration of the 5 patients who readmitted to the hospital due to heart failure was significantly shorter than that of the 11 patients without heart failure [hours: 82.0 (47.0, 99.0) vs. 116.0 (98.0, 156.0), Z = -2.381, P = 0.017].

CONCLUSIONS: On the basis of immunomodulatory and other treatments, early application of VA-ECMO in adult patients with fulminant myocarditis can significantly improve in-hospital survival rate and cardiac function. Heart failure after discharge may be related to short VA-ECMO support time during hospitalization.

PMID:36473559 | DOI:10.3760/cma.j.cn121430-20220520-00499

Stem Cells Int. 2022 Nov 23;2022:4542719. doi: 10.1155/2022/4542719. eCollection 2022.

ABSTRACT

Human induced pluripotent stem cells (hiPSCs) can be efficiently differentiated into cardiomyocytes (CMs), which can be used for cardiac disease modeling, for drug screening, and to regenerate damaged myocardium. Implementation of xeno-free culture systems is essential to fully explore the potential of these cells. However, differentiation using xeno-free adhesion matrices often results in low CM yields and lack of functional CM sheets, capable of enduring additional maturation stages. Here, we established a xeno-free CM differentiation platform using TeSR/Synthemax, including a replating step and integrated with two versatile purification/enrichment metabolic approaches. Results showed that the replating step was essential to reestablish a fully integrated, closely-knit CM sheet. In addition, replating contributed to increase the cTnT expression from 65% to 75% and the output from 2.2 to 3.1 CM per hiPSC, comparable with the efficiency observed when using TeSR/Matrigel. In addition, supplementation with PluriSin1 and Glu-Lac+ medium allowed increasing the CM content over 80% without compromising CM sheet integrity or functionality. Thus, this xeno-free differentiation platform is a reliable and robust method to produce hiPSC-derived CMs, increasing the possibility of using these cells safely for a wide range of applications.

PMID:36467280 | PMC:PMC9712013 | DOI:10.1155/2022/4542719

Crit Care. 2022 Dec 5;26(1):375. doi: 10.1186/s13054-022-04249-w.

ABSTRACT

PURPOSE: Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) can be used to restore organ perfusion in patients with cardiogenic shock until native heart recovery occurs. It may be challenging, however, to determine when patients can be weaned successfully from ECMO-surviving without requiring further mechanical support or heart transplant. We aimed to systematically review the medical literature to determine the biomarkers, hemodynamic and echocardiographic parameters associated with successful weaning of VA-ECMO in adults with cardiogenic shock and to present an evidence-based weaning algorithm incorporating key findings.

METHOD: We systematically searched PubMed, Embase, ProQuest, Google Scholars, Web of Science and the Grey literature for pertinent original research reports. We excluded studies limited to extracorporeal cardiopulmonary resuscitation (ECPR) as the neurological prognosis may significantly alter the decision-making process surrounding the device removal in this patient population. Studies with a mixed population of VA-ECMO for cardiogenic shock or cardiac arrest were included. We excluded studies limited to patients in which ECMO was only used as a bridge to VAD or heart transplant, as such patients are, by definition, never "successfully weaned." We used the Risk of Bias Assessment tool for Non-Randomized Studies. The study was registered on the International prospective register of systematic reviews (PROSPERO CRD42020178641).

RESULTS: We screened 14,578 records and included 47 that met our pre-specified criteria. Signs of lower initial severity of shock and myocardial injury, early recovery of systemic perfusion, left and right ventricular recovery, hemodynamic and echocardiographic stability during flow reduction trial and/or pump-controlled retrograde trial off predicted successful weaning. The most widely used parameter was the left ventricular outflow tract velocity time integral, an indicator of stroke volume. Most studies had a moderate or high risk of bias. Heterogeneity in methods, timing, and conditions of measurements precluded any meta-analysis.

CONCLUSIONS: In adult patients on VA-ECMO for cardiogenic shock, multiple biomarkers, hemodynamic and echocardiographic parameters may be used to track resolution of systemic hypoperfusion and myocardial recovery in order to identify patients that can be successfully weaned.

PMID:36471408 | PMC:PMC9724323 | DOI:10.1186/s13054-022-04249-w

J Cardiothorac Surg. 2022 Dec 5;17(1):296. doi: 10.1186/s13019-022-02044-w.

ABSTRACT

BACKGROUND: Saddle pulmonary embolism (SPE) represents a rare type of venous thromboembolism that frequently causes circulation collapse and sudden death. While venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been well established as a salvage treatment for SPE-induced circulatory shock, it is infrequently administered in patients with advanced malignancy, especially those with brain metastases, given the potential bleeding complications and an uncertain prognosis. As far, there are rare case reports regarding the successful management of hemodynamic instability secondary to SPE-induced cardiac arrest using VA-ECMO in advanced malignancy patients with brain metastases.

CASE PRESENTATION: A 65-year-old woman presenting with cough and waist discomfort who had a history of lung cancer with brain metastases was admitted to the hospital to receive chemoradiotherapy. She suffered sudden cardiac arrest during hospitalization and returned to spontaneous circulation after receiving a 10-min high-quality cardiopulmonary resuscitation. Pulmonary embolism was suspected due to the collapsed hemodynamics and a distended right ventricle identified by echocardiography. Subsequent computed tomographic pulmonary angiography revealed a massive saddle thrombus straddling the bifurcation of the pulmonary trunk. VA-ECMO with adjusted-dose systemic heparinization was initiated to rescue the unstable hemodynamics despite receiving thrombolytic therapy with alteplase. Immediately afterward, the hemodynamic status of the patient stabilized rapidly. VA-ECMO was successfully discontinued within 72 h of initiation without any clotting or bleeding complications. She was weaned off invasive mechanical ventilation on the 6th day of intensive care unit (ICU) admission and discharged from the ICU 3 days later with good neurological function.

CONCLUSION: VA-ECMO may be a 'bridging' therapy to circulation recovery during reperfusion therapy for SPE-induced hemodynamic collapse in malignancy patients with brain metastases.

PMID:36471400 | PMC:PMC9720990 | DOI:10.1186/s13019-022-02044-w

ASAIO J. 2022 Dec 1;68(12):1483-1489. doi: 10.1097/MAT.0000000000001692. Epub 2022 Mar 14.

ABSTRACT

Right heart failure (RHF) is a common, yet difficult to manage, complication of severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation (ECMO) that is associated with increased mortality. Reports of the use of percutaneous mechanical circulatory support devices for concurrent right heart and respiratory failure are limited. This series describes the percutaneous cannulation of the pulmonary artery for conversion from veno-venous to veno-pulmonary artery return ECMO in 21 patients who developed secondary RHF. All patients cannulated between May 2019 and September 2021 were included. Either a 19 or 21 French venous cannula was placed percutaneously into the pulmonary artery via the internal jugular or subclavian vein, providing a total of 821 days of support (median 23 [4-71] days per patient) with flows up to 6 L/min. Five patients underwent cannulation at the bedside, with the remainder performed in the cardiac catheterization laboratory. Pulmonary artery cannulation occurred after 12 [8.5-23.5] days of ECMO support. Vasoactive infusion requirements decreased significantly within 24 hours of pulmonary artery cannula placement (p = 0.0004). Nonetheless, 75% of these patients expired after a median of 12 [4-63] days of support, with three patients found to have had significant pericardial effusions peri-arrest. This cannulation technique may be an effective alternative to veno-arterial ECMO cannulation or the placement of a dual-lumen cannula for the treatment of RHF.

PMID:36469447 | DOI:10.1097/MAT.0000000000001692

Front Neurosci. 2022 Nov 18;16:952355. doi: 10.3389/fnins.2022.952355. eCollection 2022.

ABSTRACT

OBJECTIVE: Term congenital heart disease (CHD) neonates display abnormalities of brain structure and maturation, which are possibly related to underlying patient factors, abnormal physiology and perioperative insults. Our primary goal was to delineate associations between clinical factors and postnatal brain microstructure in term CHD neonates using diffusion tensor imaging (DTI) magnetic resonance (MR) acquisition combined with complementary data-driven connectome and seed-based tractography quantitative analyses. Our secondary goal was to delineate associations between mild dysplastic structural brain abnormalities and connectome and seed-base tractography quantitative analyses. These mild dysplastic structural abnormalities have been derived from prior human infant CHD MR studies and neonatal mouse models of CHD that were collectively used to calculate to calculate a brain dysplasia score (BDS) that included assessment of subcortical structures including the olfactory bulb, the cerebellum and the hippocampus.

METHODS: Neonates undergoing cardiac surgery for CHD were prospectively recruited from two large centers. Both pre- and postoperative MR brain scans were obtained. DTI in 42 directions was segmented into 90 regions using a neonatal brain template and three weighted methods. Clinical data collection included 18 patient-specific and 9 preoperative variables associated with preoperative scan and 6 intraoperative (e.g., cardiopulmonary bypass and deep hypothermic circulatory arrest times) and 12 postoperative variables associated with postoperative scan. We compared patient specific and preoperative clinical factors to network topology and tractography alterations on a preoperative neonatal brain MRI, and intra and postoperative clinical factors to network topology alterations on postoperative neonatal brain MRI. A composite BDS was created to score abnormal findings involving the cerebellar hemispheres and vermis, supratentorial extra-axial fluid, olfactory bulbs and sulci, hippocampus, choroid plexus, corpus callosum, and brainstem. The neuroimaging outcomes of this study included (1) connectome metrics: cost (number of connections) and global/nodal efficiency (network integration); (2) seed based tractography methods of fractional anisotropy (FA), radial diffusivity, and axial diffusivity. Statistics consisted of multiple regression with false discovery rate correction (FDR) comparing the clinical risk factors and BDS (including subcortical components) as predictors/exposures and the global connectome metrics, nodal efficiency, and seed based- tractography (FA, radial diffusivity, and axial diffusivity) as neuroimaging outcome measures.

RESULTS: A total of 133 term neonates with complex CHD were prospectively enrolled and 110 had analyzable DTI. Multiple patient-specific factors including d-transposition of the great arteries (d-TGA) physiology and severity of impairment of fetal cerebral substrate delivery (i.e., how much the CHD lesion alters typical fetal circulation such that the highest oxygen and nutrient rich blood from the placenta are not directed toward the fetal brain) were predictive of preoperative reduced cost (p < 0.0073) and reduced global/nodal efficiency (p < 0.03). Cardiopulmonary bypass time predicted postoperative reduced cost (p < 0.04) and multiple postoperative factors [extracorporeal membrane oxygenation (ECMO), seizures and cardiopulmonary resuscitation (CPR)] were predictive of postoperative reduced cost and reduced global/nodal efficiency (p < 0.05). Anthropometric measurements (weight, length, and head size) predicted tractography outcomes. Total BDS was not predictive of brain network topology. However, key subcortical components of the BDS score did predict key global and nodal network topology: abnormalities of the cerebellum predicted reduced cost (p < 0.0417) and of the hippocampus predicted reduced global efficiency (p < 0.0126). All three subcortical structures predicted unique alterations of nodal efficiency (p < 0.05), including hippocampal abnormalities predicting widespread reduced nodal efficiency in all lobes of the brain, cerebellar abnormalities predicting increased prefrontal nodal efficiency, and olfactory bulb abnormalities predicting posterior parietal-occipital nodal efficiency.

CONCLUSION: Patient-specific (d-TGA anatomy, preoperative impairment of fetal cerebral substrate delivery) and postoperative (e.g., seizures, need for ECMO, or CPR) clinical factors were most predictive of diffuse postnatal microstructural dysmaturation in term CHD neonates. Anthropometric measurements (weight, length, and head size) predicted tractography outcomes. In contrast, subcortical components (cerebellum, hippocampus, olfactory) of a structurally based BDS (derived from CHD mouse mutants), predicted more localized and regional postnatal microstructural differences. Collectively, these findings suggest that brain DTI connectome and seed-based tractography are complementary techniques which may facilitate deciphering the mechanistic relative contribution of clinical and genetic risk factors related to poor neurodevelopmental outcomes in CHD.

PMID:36466162 | PMC:PMC9717392 | DOI:10.3389/fnins.2022.952355