Association of Growth Differentiation Factor-15 With Event Cause and Cardiovascular Failure After Pediatric Cardiac Arrest in a Multi-Institutional Trial.
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SUBMITTER: Herrmann JR
PROVIDER: S-EPMC10492992 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Association of Growth Differentiation Factor-15 With Event Cause and Cardiovascular Failure After Pediatric Cardiac Arrest in a Multi-Institutional Trial.
Herrmann Jeremy R JR Jackson Travis C TC Fabio Anthony A Clark Robert S B RSB Berger Rachel P RP Janesko-Feldman Keri L KL Kochanek Patrick M PM Fink Ericka L EL
Journal of the American Heart Association 20230725 15
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Project description:BACKGROUND:Growth differentiation factor 15 (GDF-15) is an inflammatory cytokine released in response to tissue injury. It has prognostic value in cardiovascular diseases and other acute and chronic conditions. Here, we explored the value of GDF-15 as an early predictor of neurologic outcome after an out-of-hospital cardiac arrest (OHCA). METHODS:Prospective registry study of patients in coma after an OHCA, admitted in the intensive cardiac care unit from a single university center. Serum levels of GDF-15 were measured on admission. Neurologic status was evaluated according to the cerebral performance category (CPC) scale. The relationship between GDF-15 levels and poor neurologic outcome at 6 months was analyzed. RESULTS:Among 62 patients included, 32 (51.6%) presented poor outcome (CPC 3-5). Patients with CPC 3-5 exhibited significantly higher GDF-15 levels (median, 17.1 [IQR, 11.1-20.4] ng/mL) compared to those with CPC 1-2 (7.6 [IQR, 4.1-13.1] ng/mL; p = 0.004). Multivariable logistic regression analyses showed that age (OR, 1.09; 95% CI 1.01-1.17; p = 0.020), home setting arrest (OR, 8.07; 95% CI 1.61-40.42; p = 0.011), no bystander cardiopulmonary resuscitation (OR, 7.91; 95% CI 1.84-34.01; p = 0.005), and GDF-15 levels (OR, 3.74; 95% CI 1.32-10.60; p = 0.013) were independent predictors of poor outcome. The addition of GDF-15 in a dichotomous manner (≥ 10.8 vs. < 10.8 ng/mL) to the resulting clinical model improved discrimination; it increased the area under the curve from 0.867 to 0.917, and the associated continuous net reclassification improvement was 0.90 (95% CI 0.48-1.44), which allowed reclassification of 37.1% of patients. CONCLUSIONS:After an OHCA, increased GDF-15 levels were an independent, early predictor of poor neurologic outcome. Furthermore, when added to the most common clinical factors, GDF-15 improved discrimination and allowed patient reclassification.
| S-EPMC6797678 | biostudies-literature
Project description:Background Growth differentiation factor-15 (GDF-15) has emerged as a novel biomarker to predict all-cause death in community-dwelling individuals and patients with cardiovascular disease. We evaluated the prognostic value of GDF-15 in outpatients with cardiovascular risk factors. Methods and Results GDF-15 levels were measured in 3562 outpatients with cardiovascular risk factors in the J-HOP (Japan Morning Surge-Home Blood Pressure) study, a nationwide prospective study. Participants were stratified according to tertiles of GDF-15 and followed up for all-cause death and cardiovascular disease. During a mean follow-up period of 6.6 years, there were 155 all-cause deaths, 81 stroke events including cerebral infarction and intracranial hemorrhage, and 141 cardiac events including cardiac artery disease and heart failure. Patients with higher GDF-15 levels were associated with risks of all-cause death and stroke events (except for cardiac events) after adjustment for traditional risk factors and other prognostic biomarkers (NT-proBNP [N-terminal pro-B-type natriuretic peptide], high-sensitivity troponin T; all-cause death, hazard ratio, 2.38; 95% CI, 1.26-4.48; P=0.007; stroke events, hazard ratio, 2.93; 95% CI, 1.31-6.56, P=0.009; compared with the lowest tertile). Furthermore, incorporating GDF-15 to the predictive models for all-cause death improved discrimination and reclassification significantly. For stroke events, GDF-15 showed similar diagnostic accuracy to NT-proBNP and high-sensitivity troponin T. Conclusions In Japanese outpatients with cardiovascular risk factors, GDF-15 improves risk stratification for all-cause death when compared with NT-proBNP and high-sensitivity troponin T. GDF-15 was associated with increased risks of stroke events beyond conventional risk factors and other prognostic markers; however, the predictive ability for stroke events was equivalent to NT-proBNP and high-sensitivity troponin T. Registration URL: http://www.umin.ac.jp/ctr.; Unique identifier: UMIN000000894.
| S-EPMC9075247 | biostudies-literature
Project description:ObjectivesIn-hospital cardiac arrest occurs in 2.6-6% of children with cardiac disease and is associated with significant morbidity and mortality. Much remains unknown about cardiac arrest in pediatric cardiac ICUs; therefore, we aimed to describe cardiac arrest epidemiology in a contemporary multicenter cardiac ICU cohort.DesignRetrospective analysis within the Pediatric Cardiac Critical Care Consortium clinical registry.SettingCardiac ICUs within 23 North American hospitals.PatientsAll cardiac medical and surgical patients admitted from August 2014 to July 2016.InterventionsNone.Measurements and main resultsThere were 15,908 cardiac ICU encounters (6,498 medical, 9,410 surgical). 3.1% had cardiac arrest; rate was 4.8 cardiac arrest per 1,000 cardiac ICU days. Medical encounters had 50% higher rate of cardiac arrest compared with surgical encounters. Observed (unadjusted) cardiac ICU cardiac arrest prevalence varied from 1% to 5.5% among the 23 centers; cardiac arrest per 1,000 cardiac ICU days varied from 1.1 to 10.4. Over half cardiac arrest occur within 48 hours of admission. On multivariable analysis, prematurity, neonatal age, any Society of Thoracic Surgeons preoperative risk factor, and Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery mortality category 4, 5 had strongest association with surgical encounter cardiac arrest. In medical encounters, independent cardiac arrest risk factors were acute heart failure, prematurity, lactic acidosis greater than 3 mmol/dL, and invasive ventilation 1 hour after admission. Median cardiopulmonary resuscitation duration was 10 minutes, return of spontaneous circulation occurred in 64.5%, extracorporeal cardiopulmonary resuscitation in 27.2%. Unadjusted survival was 53.2% in encounters with cardiac arrest versus 98.2% without. Medical encounters had lower survival after cardiac arrest (37.7%) versus surgical encounters (62.5%); Norwood patients had less than half the survival after cardiac arrest (35.6%) compared with all others. Unadjusted survival after cardiac arrest varied greatly among 23 centers.ConclusionsWe provide contemporary epidemiologic and outcome data for cardiac arrest occurring in the cardiac ICU from a multicenter clinical registry. As detailed above, we highlight high-risk patient cohorts and periods of time that may serve as targets for research and quality improvement initiatives aimed at cardiac arrest prevention.
| S-EPMC5628130 | biostudies-literature
Project description:BackgroundPediatric out-of-hospital cardiac arrest (POHCA) has received limited attention. All causes of POHCA and outcomes were examined during a 4-year period in a Danish nationwide register and prehospital medical records. The aim was to describe the incidence, reversible causes, and survival rates for POHCA in Denmark.MethodsThis is a registry-based follow-up cohort study. All POHCA for a 4-year period (2016-2019) in Denmark were included. All prehospital medical records for the included subjects were reviewed manually by five independent raters establishing whether a presumed reversible cause could be assigned.ResultsWe identified 173 cases within the study period. The median incidence of POHCA in the population below 17 years of age was 4.2 per 100,000 persons at risk. We found a presumed reversible cause in 48.6% of cases, with hypoxia being the predominant cause of POHCA (42.2%). The thirty-day survival was 40%. Variations were seen across age groups, with the lowest survival rate in cases below 1 year of age. Defibrillators were used more frequently among survivors, with 16% of survivors defibrillated bystanders as opposed to 1.9% in non-survivors and 24% by EMS personnel as opposed to 7.8% in non-survivors. The differences in initial rhythm being shockable was 34% for survivors and 16% for non-survivors.ConclusionWe found pediatric out-of-hospital cardiac arrests was a rare event, with higher incidence and mortality in infants compared to other age groups of children. Use of defibrillators was disproportionally higher among survivors. Hypoxia was the most common presumed cause among all age groups.
| S-EPMC9670404 | biostudies-literature
Project description:Sonographic cardiac standstill during adult cardiac arrest is associated with failure to get return to spontaneous circulation. This report documents 3 children whose cardiac function returned after standstill with extracorporeal membranous oxygenation. Sonographic cardiac standstill may not predict cardiac death in children.
| S-EPMC5790592 | biostudies-literature
Project description:ImportanceThe Pediatric Cardiac Critical Care Consortium (PC4) cardiac arrest prevention (CAP) quality improvement (QI) project facilitated a decreased in-hospital cardiac arrest (IHCA) incidence rate across multiple hospitals. The sustainability of this outcome has not been determined.ObjectiveTo examine the IHCA incidence rate at participating hospitals after the QI project ended and discern which factors best aligned with sustained improvement.Design, setting, and participantsThis observational cohort study compared IHCA data from the CAP era (July 1, 2018, to December 31, 2019) with data from the 2-year follow-up era (March 1, 2020, to February 28, 2022). Data were obtained from pediatric cardiac intensive care units (CICUs) from 17 PC4 CAP-participating hospitals.InterventionThe CAP practice bundle was designed to facilitate local practice integration, with the intention to implement, adapt, and continue CAP processes beyond the CAP era. A web-based survey was administered 2 years after the end of the project to estimate CAP-specific QI work.Main outcomes and measuresRisk-adjusted IHCA incidence rates across all admissions were compared between study eras. The survey generated a novel hospital-specific QI sustainability score, which is generally reflective of the sum of local CAP work performed.ResultsThere were no clinically important differences in demographic and admission characteristics between the 13 082 CAP era admissions and 16 284 follow-up admissions (total mean [SD] age, 5.1 [8.4] years; 56.1% male). Risk-adjusted IHCA incidences were not different between the CAP vs follow-up eras (2.8% vs 2.8%; odds ratio, 1.03; 95% CI, 0.89-1.19), suggesting sustained prevention improvement. There was also no difference between eras in risk-adjusted IHCA incidence within medical, surgical, or high-risk subgroups. A lower hospital QI sustainability score was correlated with higher odds for IHCA in the follow-up vs CAP era (correlation coefficient, -0.58; P = .02). Five hospitals had increases of 1% or greater in risk-adjusted IHCA rates in the follow-up era; these hospitals had significantly lower QI sustainability scores and were less likely to have adopted sustainability elements during the CAP era or report persistent engagement for CAP-related QI processes during follow-up.Conclusions and relevanceIn this cohort study of all CICU admissions across 17 hospitals, IHCA prevention was feasible and sustainable; the established reduction in risk-adjusted IHCA rate was maintained for at least 2 years after the end of the CAP project. Both implementation strategies and continued engagement in CAP processes during the follow-up era were associated with sustained improvement.
| S-EPMC11385048 | biostudies-literature
Project description:This study aimed to evaluate the effects of cardiac rehabilitation (CR) on major adverse cardiac events (MACE) among patients who underwent PCI procedure. We used data from the electronic medical records (EMR) of a tertiary hospital in Seoul, Korea, from January 2014 to February 2020. Data from 2988 patients who had experienced their first acute coronary syndrome (ACS) and had undergone percutaneous coronary intervention (PCI) were included during the study period. we classified patients into CR participants and non-participants based on their participation in the cardiac rehabilitation (CR) program within 30 days after discharge. And the outcome was the incidence of myocardial infarction (MI) and stroke within 1 year after discharge. The association between participation in CR and risk of developing MACE was evaluated using the Cox proportional hazards model. Patients who achieved CR after undergoing PCI were at a lower risk of developing MI (HR 0.68, CI 0.53-0.86). There was no significant association between participation in CR and the incidence of stroke. Among patients who had more than three stenotic vessels, the risk of developing MI within 1 year of discharge was reduced in CR users compared to non-users (3 or more stenosis vessels: HR 0.55, CI 0.35-0.86). Among patients who used two and more stents during PCI procedures, the risk of developing MI within 1 year of discharge was reduced in CR users compared to non-users (2 and more stents: HR 0.54, CI 0.35-0.85). Among people diagnosed with ACS and receiving PCI, patients who participated in CR within one month of discharge reduced risk of developing MI. Our study reinforced the current evidence on the effect of CR among patients receiving PCI and presented the expansion and enhancement of the CR program.
| S-EPMC10628201 | biostudies-literature
Project description: Not available
| S-EPMC11253404 | biostudies-literature
Project description:Sudden unexpected death in infancy occurs in apparently healthy infants and remains largely unexplained despite thorough investigation. The vast majority of cases are sporadic. Here we report seven individuals from three families affected by sudden and unexpected cardiac arrest between 4 and 20 months of age. Whole-exome sequencing revealed compound heterozygous missense mutations in PPA2 in affected infants of each family. PPA2 encodes the mitochondrial pyrophosphatase, which hydrolyzes inorganic pyrophosphate into two phosphates. This is an essential activity for many biosynthetic reactions and for energy metabolism of the cell. We show that deletion of the orthologous gene in yeast (ppa2Δ) compromises cell viability due to the loss of mitochondria. Expression of wild-type human PPA2, but not PPA2 containing the mutations identified in affected individuals, preserves mitochondrial function in ppa2Δ yeast. Using a regulatable (doxycycline-repressible) gene expression system, we found that the pathogenic PPA2 mutations rapidly inactivate the mitochondrial energy transducing system and prevent the maintenance of a sufficient electrical potential across the inner membrane, which explains the subsequent disappearance of mitochondria from the mutant yeast cells. Altogether these data demonstrate that PPA2 is an essential gene in yeast and that biallelic mutations in PPA2 cause a mitochondrial disease leading to sudden cardiac arrest in infants.
| S-EPMC5010643 | biostudies-literature
Project description:Background and aimPrevious studies have documented that the association between growth differentiation factor-15 (GDF-15) the risk of patients with cardiovascular diseases (CVDs). In this meta-analysis, our main objective is to explore the associations between GDF-15 and the risk of CVD or all-cause mortality.MethodsPubMed and ISI Web of Science (up to January 2018) electronic databases were browsed for eligible studies. The studies provided relevant data depicted as hazard ratio (HR) with 95% confidence interval (CI), with regard to the association between GDF-15 levels and subsequent risk of CVDs or all-cause mortality. A random-effect model was applied to pool the HR and 95% CI.ResultsThirty-one prospective studies met the eligibility criteria involving 53 706 subjects with 7020 adverse outcome events. It was concluded that GDF-15 levels were associated with an incremental risk of CVDs or all-cause mortality. Highest GDF-15 category was associated with greater risk of cardiovascular mortality (HR, 2.66; 95% CI, 1.69-3.63), all-cause mortality (HR, 2.52; 95% CI, 2.06-2.97), and complex adverse outcome (HR, 1.81; 95% CI, 1.42-2.21). As each log-unit increment in GDF-15 concentration, the corresponding risk of adverse events also escalated, cardiovascular mortality (HR, 2.11; 95% CI, 1.57-2.66), all-cause mortality (HR, 2.70; 95% CI, 2.29-3.12), and complex adverse outcome (HR, 1.96; 95% CI, 1.64-2.29).ConclusionsJudging from the results of the data analysis, GDF-15 levels may increase the risk of CVDs or all-cause mortality.
| S-EPMC6523003 | biostudies-literature