Primary Outcome Of Death Research Articles

Restrictive Versus Liberal Transfusion in Patients With Type 1 or Type 2 Myocardial Infarction: A Prespecified Analysis of the MINT Trial.

The MINT trial (Myocardial Ischemia and Transfusion) raised concern for harm from a restrictive versus liberal transfusion strategy in patients with acute myocardial infarction (MI) and anemia. Type 1 and type 2 MI are distinct pathophysiologic entities that may respond differently to blood transfusion. This analysis sought to determine whether the effects of transfusion varied among patients with a type 1 or a type 2 MI and anemia. The authors hypothesized that the liberal transfusion strategy would be of greater benefit in type 2 than in type 1 MI. The authors compared rates of death or MI at 30 days in patients with type 1 (n=1460) and type 2 (n=1955) MI and anemia who were randomly allocated to a restrictive (threshold, 7-8 g/dL) or a liberal (threshold, 10 g/dL) transfusion strategy. The primary outcome of death or MI was observed in 16% of type 1 MI and 15.4% of type 2 MI patients. The rate of death or MI was higher in patients with type 1 MI randomized to a restrictive (18.2%) versus liberal (13.8%) transfusion strategy (relative risk [RR], 1.32 [95% CI, 1.04-1.67]) with no difference observed between the restrictive (15.8%) and liberal (15.1%) transfusion strategies in patients with type 2 MI (RR, 1.05 [95% CI, 0.85-1.29]). The test for a differential effect of transfusion strategy by MI type was not statistically significant (Pinteraction = 0.16). The concern for harm with a restrictive transfusion strategy in patients with acute MI and anemia raised in the MINT primary outcome manuscript may be more apparent in patients with type 1 than type 2 MI. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02981407.

Comparison between coronary calcium score and segment involvement score when used in clinical routine

Abstract Data from a nationwide registry on coronary computer tomography angiography. Background The Coronary Artery Calcium Score (CACS) and segment involvement score (SIS) are crucial factors in assessing the severity of coronary artery disease (CAD) and determining the likelihood of future cardiovascular events. However, there are few large multicenter studies comparing the predictive value of CACS and SIS when used in the clinical routine. Objectives To compare CACS and SIS ability to predict cardiovascular outcomes when used in the clinical routine. Methods This retrospective cohort study included patients who underwent Coronary Computed Tomography Angiography (CCTA) for CAD evaluation between 2006-2022 in 29 different centers in Sweden. CACS was calculated using the Agatston method, and SIS was determined based on the number of coronary segments exhibiting plaque. For SIS, patients were categorized into SIS=0, SIS=1, SIS=2, SIS=3, SIS³4, for CACS patients were categorized into CACS=0, CACS=1-9, CACS=10-99, CACS=100-299, CACS³300. Patients were followed regarding the primary outcome of death or myocardial infarction. Multivariable Cox proportional hazards models were used for adjusting for potential confounders. Results A total of 23034 patients underwent CCTA and were followed for up to ten years. Median age (IQR) was 58 (49–67) years, 50% were women, 9% had diabetes mellitus, 42% had hypertension, 25% had hyperlipidemia, 5% had previously known CAD. There were 955 patients (4.1%) with myocardial infarction (MI) and 409 patients (2.2%) died during follow up. There was an increase in cardiovascular events with increasing SIS. When comparing SIS and presence of obstructive stenosis, SIS was a better predictor of outcome (Figure 1). There was also an increase cardiovascular events with increasing CACS (Figure 2). When adjusted for age, sex, risk factors, previous cardiovascular disease and intervention, both SIS and CACS were independently associated with outcome. When SIS and CACS were compared in a receiver operating characteristic curve, CACS had significantly larger AUC than SIS, (0.70[0.67-0.73] vs 0.62[0.60-0.63]). Conclusion Our findings show that both CACS and SIS are important and independent predictors of cardiovascular outcomes thereby offering a valuable tool for personalized risk stratification and management in clinical settings. When used in the clinical routine, CACS appears to be more strongly associated with outcome than SIS.Figure1 Survival SISFigure 2 Survival CACS

Long term follow up in pulmonary embolism: can right ventricular strain echocardiographic imaging contribute to refine risk stratification?

Abstract Background In pulmonary embolism (PE), the usual evaluation of early risk of death includes clinical, biological and two-dimensional right ventricular (RV) echocardiographic (TTE) parameters. Purpose We hypothesized that myocardial strain analysis could contribute to risk of death prediction at long term follow up. Methods We retrospectively analyzed 477 patients hospitalized for acute EP. Usual parameters used to define RV dysfunction were evaluated using TTE (RV dilatation, systolic pulmonary arterial pressure, TAPSE, S’, Fractionnal Area Change (FAC), end diastolic RV diameter and right atrial, RA, area). In addition, we evaluated, left ventricle (LV) longitudinal, left atrial (LA), RA and RV free wall strains. Patients without history of cancer (n=419) were analyzed on the primary outcome of death at long term follow up. Results Mean of age was 63.7 ± 17.2 years and 227 (47.6) patients were male. The main clinical and echocardiographic characteristics are displayed in the Table 1. During a mean follow-up was 45.0 ± 16.6 months, the primary outcome occurred in 56 patients. In multivariable analysis, systolic pulmonary arterial pressure, indexed right atrial and left atrial volumes, right ventricle free wall strain, right ventricle global longitudinal strain were the only predictors of death (Table 2). Conclusion Atrial volumes and RV strain appeared as strong predictors of death in PE at long term follow up. Right ventricle myocardial strain analysis should be evaluated in each patient hospitalized for PE.

Prenatal Prognosis of Omphalocele Using Magnetic Resonance Imaging Measurement of Fetal Lung Volumes

BackgroundOmphalocele is a congenital midline abdominal wall defect resulting in herniation of viscera into a membrane-covered sac. Pulmonary complications, including pulmonary hypoplasia, pulmonary hypertension, and prolonged respiratory support are a leading cause of neonatal morbidity and mortality. Objective(s)This study aimed to assess the role of fetal MRI-derived lung volumes and omphalocele defect size as clinical tools to prognosticate postnatal pulmonary morbidity and neonatal mortality in those with a prenatally diagnosed omphalocele (PDO). Study DesignThis was a retrospective cohort study of all pregnancies with PDO at our fetal center from 2007–2023. Pregnancies with aneuploidy or concurrent life-limiting fetal anomalies were excluded. Using fetal MRI, observed-to-expected total fetal lung volume (O/E TLV) ratios were determined by a previously published method. The transverse diameter of the abdominal defect was also measured. The O/E TLV ratios and abdominal defect measurements were compared with postnatal outcomes. The primary outcome was death at any time. Secondary outcomes included death in the first 30 days of life or before discharge from birth hospitalization, the requirement of respiratory support with intubation and mechanical ventilation, or development of pulmonary hypertension. ResultsOf 101 pregnancies with a PDO, 54 pregnancies (53.5%) with prenatally diagnosed omphalocele met inclusion criteria. There was a significant increase in the rate of death when compared between the three O/E TLV classifications: 1/36 (2.8%) in the O/E≥50% group, 3/14 (21.4%) in the O/E 25%–49.9% group, and 4/4 (100%) in the O/E<25% group (P<.001). The rate of intubation increased with the severity of O/E TLV classification, with 27.8% in the O/E≥50% group, 64.3% in the O/E 25%–49.9% group, and 100% in the O/E<25% group (P=.003). The rate of pulmonary hypertension was also higher in the O/E 25%–49.9% (50.0%) and the O/E<25% (50.0%) groups compared to the O/E≥50% group (8.3%, P=.002). There was no association between the transverse diameter of the abdominal wall defect and the primary outcome of death (OR=1.08 95% CI=[0.65–1.78], P=.77). ConclusionsIn our cohort of patients with PDO, O/E TLV<50% is associated with death, need for intubation, prolonged intubation, and pulmonary hypertension. In contrast, omphalocele size demonstrated no prognostic value for these outcomes. The strong association between low fetal lung volume on MRI and poor neonatal outcomes highlights the utility of fetal MRI for estimating postnatal prognosis. Clinicians can utilize fetal lung volumes to direct perinatal counseling and optimize the plan of care.

Time to Reaching Target Cooling Temperature and 2-year Outcomes in Infants with Hypoxic-Ischemic Encephalopathy

To determine if time to reaching target temperature (TT) is associated with death or neurodevelopmental impairment (NDI) at 2years of age in infants with hypoxic-ischemic encephalopathy (HIE). Newborn infants ≥36weeks of gestation diagnosed with moderate or severe HIE and treated with therapeutic hypothermia were stratified based on time at which TT was reached, defined as early (ie, ≤4hours of age) or late (>4hours of age). Primary outcomes were death or NDI. Secondary outcomes included neurodevelopmental assessment with Bayley Scales of Infant and Toddler Development, third edition (BSID-III) at age2. Among 500 infants, the median time to reaching TT was 4.3 hours (IWR, 3.2-5.7 hours). Infants in early TT group (n=211 [42%]) compared with the late TT group (n=289 [58%]) were more likely to be inborn (23% vs 13%; P<.001) and have severe HIE (28% vs 19%; P=.03). The early and late TT groups did not differ in the primary outcome of death or any NDI (adjusted RR,1.05; 95% CI,0.85-0.30; P=.62). Among survivors, neurodevelopmental outcomes did not differ significantly in the 2 groups (adjusted mean difference in Bayley Scales of Infant Development-III scores: cognitive, -2.8 [95% CI,-6.1 to 0.5], language -3.3 [95% CI,-7.4 to 0.8], and motor -3.5 [95% CI,-7.3 to 0.3]). In infants with HIE, time to reach TT is not independently associated with risk of death or NDI at age 2years. Among survivors, developmental outcomes are similar between those who reached TT at <4 and ≥4 hours of age. High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL); NCT02811263; https://beta. gov/study/NCT02811263.

The Clinical Profile and Prognostic Factors Influencing Mortality in Patients With Acute Encephalitis Syndrome.

Introduction Acute encephalitis syndrome (AES) is a significant global public health concern. AES is a disorder characterized by fever and altered mental status, and it is associated with considerable morbidity and mortality. There is a limited amount of existing literature on the clinical profile and prognostic markers that influence mortality in these patients. Our study seeks to comprehend the etiology, clinical characteristics, complications, and prognostic markers that impact mortality among patients with AES. Methods The study was a prospective observational study conducted over 18 months, involving a sample size of 105 patients. Patients aged 12 years and older, who met the WHO case definition of Acute Encephalitis Syndrome (AES), were consecutively recruited for this study. The patients' details were recorded, including their medical historyand physical and clinical examination findings upon admission. The extent of cognitive impairment was evaluated using the Glasgow Coma Scale (GCS). Additionally, the patient's presenting symptoms, any complications experienced during their hospital stay, and the mortality rate were documented. The etiology, MRI results of the brain, laboratory parameters, and the need for assisted ventilation were also recorded.In-hospital characteristics were analyzed using the t-test for continuous variables and the chi-square test for binary variables. The log-rank test was employed to identify the predictors with the most significant independent influence on prognosis. All participants were selected only after obtaining their written informed consent. Results Most of the patients were in the age group of 21-30. 60% of the patients were male. Advanced age at presentation was associated with an increased risk of mortality (p-value=0.018). All patients presented to the hospital with symptoms of fever and altered sensorium. The most common agent isolated as the etiologic cause was HSV-1, found in 31.4% of the patients. 28.6% of the patients succumbed to death. The leading cause of death was raised intracranial pressure leading to hemorrhage in the brain. There was no significant correlation between the duration of symptoms and the primary outcome of death (p-value=0.498). The requirement for assisted ventilation was shown to increase the risk of death (p-value=0.001). A low GCS score at presentation was associated with a higher mortality rate (p-value=0.048). Conclusions The factors that predict mortality in AES involve a complex interplay of patient demographics, viral etiology, clinical severity, neuroimaging findings, and the need for assisted ventilation. Integrating these factors into clinical practice would enable healthcare providers to make informed decisions regarding patient management and interventions. As our comprehension of AES continues to develop, forthcoming advancements in diagnostics and therapeutics could refine prognostic assessments further. These developments could open new avenues for enhancing outcomes and diminishing mortality rates in this complex neurological disorder.

The prevalence and importance of frailty in cardiac resynchronization therapy patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Nemzeti Kardiovaszkuláris Laboratórium RRF-2.3.1-21-2022-00003. Background Frailty, characterized by loss of homeostatic reserves and increased vulnerability to physiological decompensation, results from an aggregation of insults across multiple organ systems. Frailty can be quantified by counting the number of ‘health deficits’ across a range of domains. Aims We assessed the frequency of, and outcomes related to frailty in patients with heart failure and reduced ejection fraction who previously underwent cardiac resynchronization therapy (CRT) implantation. Methods We used a cumulative deficits approach to construct a 30-item frailty index (FI) and applied it to identify frail patients enrolled in our CRT registry. The 30 items were derived from medical history, other patient characteristics and laboratory results, covering a range of body systems. In keeping with previous studies, patients with FI ≤0.210 were classified as non-frail and those with higher scores were divided into two categories using score increments of 0.100. Our primary endpoint was all-cause mortality. Results Among 1004 included patients, 75 (7%) were considered Non-frail, while 271 (27%) and 658 (66%) participants were categorized as Frail in groups 1- and 2. Patients in Frail group 2 were older, had a less favorable renal function, and generally had more comorbidities (i.e. atrial fibrillation, hypertension, ischemic cardiovascular disease) than patients categorized in the Non-frail or Frail group 1. During the median follow-up time of 4.4 (2.3-6.9) years, 17 (22%) patients in the Non-frail group, 103 (38%) in Frail group 1, and 479 (73%) in the Frail group 2 reached the primary endpoint. Non-frail patient group showed the most beneficial survival with a 70% (HR 0.31; 95% CI: 0.23-0.41; p&amp;lt;0.001) lower all-cause mortality risk compared to Frail group 2. Adjusting for relevant covariates, NYHA class, creatinine, and TAPSE were identified as independent predictors for all-cause mortality. Conclusion Based on our results, CRT candidates are exceedingly vulnerable with a high prevalence of frailty. The calculated frailty index was associated with the primary outcome of death from any cause. FI proved to be prevalent in individual risk stratification and can predict the outcome.

Delayed versus immediate cord clamping in dichorionic twins

Objectives Strong evidence imply that delayed cord clamping (DCC) provides significant benefits for singleton neonates. However, there is little information about the safety or efficacy of DCC in twins to recommend for or against DCC in twins in guidelines. We aimed to determine the effect of DCC on dichorionic twins born at <32 weeks of gestation. Study design This is a retrospective cohort study comparing the neonatal and maternal outcomes of immediate cord clamping (ICC) [<15 second (s)] versus DCC (at 60 s). Generalized estimating equations models were performed accounting for twin correlation. Results A total of 82 pairs of twins (DCC: 41; ICC: 41) were included in analysis. The primary outcome of death before discharge occurred in 3.66% of twins in the DCC group and 7.32% in the ICC group, without a significant difference between the groups. Compared to ICC group, DCC was associated with increased hemoglobin levels [β1 coefficient 6.51; 95% confidence interval (CI) 0.69–12.32. β2 coefficient 5.80; 95% CI 0.07–11.54] at 12–24 h of life. There were no significant differences between the groups in neonatal death, neonatal major morbidities and maternal bleeding complications, although DCC was associated with higher estimated maternal blood loss in the cesarean section group (p = .005). Conclusions DCC for 60 s in dichorionic twins born at <32 weeks of gestation was associated with increased neonatal hemoglobin levels, when compared with ICC. The finding of a higher estimated maternal blood loss by cesarean section in the DCC group calls for further trials to assess maternal safety of this procedure in this patient population.

Evaluation of heterogeneity in effect of therapeutic hypothermia by sex among infants with neonatal encephalopathy.

Our objective was to examine heterogeneity in the effect of therapeutic hypothermia by sex in infants with moderate or severe neonatal encephalopathy. We conducted a post hoc analysis of the Induced Hypothermia trial, which included infants born at gestational ages ≥36 weeks, admitted at ≤6 postnatal hours with evidence of severe acidosis or perinatal complications and moderate or severe neonatal encephalopathy. Multivariate modified Poisson regression models were used to compare the treatment effect of whole-body hypothermia versus control, with an evaluation of interaction by sex, on the primary outcome of death or moderate or severe disability at 18-22 months of corrected age. A total of 101 infants (51 male, 50 female) were randomly assigned to hypothermia treatment and 104 infants (64 male, 40 female) to control. The primary outcome occurred in 45% of the hypothermia group and 63% of the control group (RR 0.73; 95% CI 0.56, 0.94). There was no significant difference (interaction P = 0.50) in the treatment effect of hypothermia on the primary outcome between females (RR 0.79; 95% CI 0.54, 1.17) compared to males (RR 0.63; 95% CI 0.44, 0.91). We found no evidence that sex influences the treatment effect of hypothermia in infants with moderate or severe neonatal encephalopathy. Preclinical evidence suggests a differential effect in response to cooling treatment of hypoxic-ischemic injury between males and females. We found no evidence of heterogeneity in the treatment effect of whole-body hypothermia by sex in this post hoc subgroup analysis of infants with moderate or severe neonatal encephalopathy from the National Institute of Child Health and Human Development Neonatal Research NetworkInduced Hypothermia trial.

Computed tomography body composition and clinical outcomes following lung transplantation in cystic fibrosis

BackgroundLow muscle mass is common in patients approaching lung transplantation and may be linked to worse post-transplant outcomes. Existing studies assessing muscle mass and post-transplant outcomes include few patients with cystic fibrosis (CF).MethodsBetween May 1993 and December 2018, 152 adults with CF received lung transplants at our institution. Of these, 83 met inclusion criteria and had usable computed tomography (CT) scans. Using Cox proportional hazards regression, we evaluated the association between pre-transplant thoracic skeletal muscle index (SMI) and our primary outcome of death after lung transplantation. Secondary outcomes, including days to post-transplant extubation and post-transplant hospital and intensive care unit (ICU) length of stay, were assessed using linear regression. We also examined associations between thoracic SMI and pre-transplant pulmonary function and 6-min walk distance.ResultsMedian thoracic SMI was 26.95 cm2/m2 (IQR 23.97, 31.32) for men and 22.83 cm2/m2 (IQR 21.27, 26.92) for women. There was no association between pre-transplant thoracic SMI and death after transplant (HR 1.03; 95% CI 0.95, 1.11), days to post-transplant extubation, or post-transplant hospital or ICU length of stay. There was an association between pre-transplant thoracic SMI and pre-transplant FEV1% predicted (b = 0.39; 95% CI 0.14, 0.63), with higher SMI associated with higher FEV1% predicted.ConclusionsSkeletal muscle index was low for men and women. We did not identify a significant relationship between pre-transplant thoracic SMI and post-transplant outcomes. There was an association between thoracic SMI and pre-transplant pulmonary function, confirming the potential value of sarcopenia as a marker of disease severity.

Clinical Outcome of Ultrasound-Detected Perforated Necrotizing Enterocolitis without Radiographic Pneumoperitoneum in Very Preterm Infants

To investigate the clinical outcomes of ultrasound (US)-detected perforated necrotizing enterocolitis (NEC) without radiographic pneumoperitoneum in very preterm infants. In this single-center retrospective study, very preterm infants who underwent a laparotomy for perforated NEC during their neonatal intensive care unit stay were classified into two groups according to the absence or presence of pneumoperitoneum on radiographs (the case versus the control groups). The primary outcome was death before discharge, and the secondary outcomes included major morbidities and body weight at 36 weeks postmenstrual age (PMA). Of the 57 infants with perforated NEC, 12 (21%) had no pneumoperitoneum on the radiographs and were diagnosed with perforated NEC on the US. In the multivariable analyses, the primary outcome of death before discharge was significantly lower in infants with perforated NEC without radiographic pneumoperitoneum than in those with perforated NEC and radiographic pneumoperitoneum (8% [1/12] vs. 44% [20/45]; adjusted odds ratio [OR], 0.02; 95% confidence interval [CI], 0.00-0.61; p = 0.025). The secondary outcomes (short bowel syndrome, total parenteral nutrition dependence for 3 months or more, the length of their hospital stay, a bowel stricture requiring surgery, sepsis after the laparotomy, acute kidney injury after the laparotomy, and body weight at 36 weeks PMA) did not differ significantly between the two groups. Very preterm infants with US-detected perforated NEC without radiographic pneumoperitoneum had a lower risk of death before discharge than those with perforated NEC and radiographic pneumoperitoneum. Bowel USs may have a potential role in surgical decision-making in infants with advanced NEC.

Incidence of death or disability at 6 months after extracorporeal membrane oxygenation in Australia: a prospective, multicentre, registry-embedded cohort study

Extracorporeal membrane oxygenation (ECMO) is an invasive procedure used to support critically ill patients with the most severe forms of cardiac or respiratory failure in the short term, but long-term effects on incidence of death and disability are unknown. We aimed to assess incidence of death or disability associated with ECMO up to 6 months (180 days) after treatment. This prospective, multicentre, registry-embedded cohort study was done at 23 hospitals in Australia from Feb 15, 2019, to Dec 31, 2020. The EXCEL registry included all adults (≥18 years) in Australia who were admitted to an intensive care unit (ICU) in a participating centre at the time of the study and who underwent ECMO. All patients who received ECMO support for respiratory failure, cardiac failure, or cardiac arrest during their ICU stay were eligible for this study. The primary outcome was death or moderate-to-severe disability (defined using the WHO Disability Assessment Schedule 2.0, 12-item survey) at 6 months after ECMO initiation. We used Fisher's exact test to compare categorical variables. This study is registered with ClinicalTrials.gov, NCT03793257. Outcome data were available for 391 (88%) of 442 enrolled patients. The primary outcome of death or moderate-to-severe disability at 6 months was reported in 260 (66%) of 391 patients: 136 (67%) of 202 who received veno-arterial (VA)-ECMO, 60 (54%) of 111 who received veno-venous (VV)-ECMO, and 64 (82%) of 78 who received extracorporeal cardiopulmonary resuscitation (eCPR). After adjustment for age, comorbidities, Acute Physiology and Chronic Health Evaluation (APACHE) IV score, days between ICU admission and ECMO start, and use of vasopressors before ECMO, death or moderate-to-severe disability was higher in patients who received eCPR than in those who received VV-ECMO (VV-ECMO vs eCPR: risk difference [RD] -32% [95% CI -49 to -15]; p&lt;0·001) but not VA-ECMO (VA-ECMO vs eCPR -8% [-22 to 6]; p=0·27). In our study, only a third of patients were alive without moderate-to-severe disability at 6 months after initiation of ECMO. The finding that disability was common across all areas of functioning points to the need for long-term, multidisciplinary care and support for surviving patients who have had ECMO. Further studies are needed to understand the 180-day and longer-term prognosis of patients with different diagnoses receiving different modes of ECMO, which could have important implications for the selection of patients for ECMO and management strategies in the ICU. The National Health and Medical Research Council of Australia.

Clinical outcomes of conduction system pacing compared to biventricular pacing in patients requiring cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is well-established therapy in patients with reduced left ventricular ejection fraction (LVEF) and bundle branch block or indication for pacing. Conduction system pacing (CSP) using His-bundle pacing (HBP) or left bundle branch area pacing (LBBAP) has been shown to be a safe and more physiological alternative to BVP. The purpose of this study was to compare the clinical outcomes between CSP and BVP among patients undergoing CRT. This observational study included consecutive patients with LVEF ≤35% and class I or II indications for CRT who underwent successful BVP or CSP at 2 major health care systems. The primary outcome was the composite endpoint of time to death or heart failure hospitalization (HFH). Secondary outcomes included subgroup analysis in left bundle branch block as well as individual endpoints of death and HFH. A total of 477 patients (32% female) met inclusion criteria (BVP 219; CSP 258 [HBP 87, LBBAP 171]). Mean age was 72 ± 12 years, and mean LVEF was 26% ± 6%. Comorbidities included hypertension 70%, diabetes mellitus 45%, and coronary artery disease 52%. Paced QRS duration in CSP was significantly narrower than BVP (133 ± 21 ms vs 153 ± 24 ms; P <.001). LVEF improved in both groups during mean follow-up of 27 ± 12 months and was greater after CSP compared to BVP (39.7% ± 13% vs 33.1% ± 12%; P <.001). Primary outcome of death or HFH was significantly lower with CSP vs BVP (28.3% vs 38.4%; hazard ratio 1.52; 95% confidence interval 1.082-2.087; P = .013). CSP improved clinical outcomes compared to BVP in this large cohort of patients with indications for CRT.

Presentation cardiac troponin and early computed tomography coronary angiography in patients with suspected acute coronary syndrome: a pre-specified secondary analysis of the RAPID-CTCA trial.

AimsTo evaluate the potential associations between presentation cardiac troponin and the clinical impact of early computed tomography coronary angiography (CTCA) in intermediate-risk patients with suspected acute coronary syndrome.Methods and resultsIn a large multicentre randomized controlled trial of patients with intermediate-risk chest pain due to suspected acute coronary syndrome, early CTCA had no effect on the primary outcome—death or subsequent Type 1 or 4b myocardial infarction—but reduced the rate of invasive coronary angiography. In this pre-specified secondary analysis, cardiovascular testing and clinical outcomes were compared between those with or without cardiac troponin elevation at presentation. Of 1748 patients, 1004 (57%) had an elevated cardiac troponin concentration and 744 (43%) had a normal concentration. Patients with cardiac troponin elevation had a higher Global Registry of Acute Coronary Events score (132 vs. 91; P < 0.001) and were more likely to have obstructive coronary artery disease (59 vs. 33%; P < 0.001), non-invasive (72 vs. 52%; P < 0.001) and invasive (72 vs. 38%; P < 0.001) testing, coronary revascularization (47 vs. 15%; P < 0.001), and the primary outcome (8 vs. 3%; P = 0.007) at 1 year. However, there was no evidence that presentation cardiac troponin was associated with the relative effects of early CTCA on rates of non-invasive (Pinteraction = 0.33) and invasive (Pinteraction = 0.99) testing, coronary revascularization (Pinteraction = 0.57), or the primary outcome (Pinteraction = 0.41).ConclusionPresentation cardiac troponin had no demonstrable associations between the effects of early CTCA on reductions in non-invasive and invasive testing, or the lack of effect on coronary revascularization or the primary outcome in intermediate-risk patients with suspected acute coronary syndrome.

Intervening on the storage time of RBC units and its effects on adverse recipient outcomes using real-world data

AbstractRandomized controlled trials (RCTs) have found no evidence that the storage time of transfused red blood cell (RBC) units affects recipient survival. However, inherent difficulties in conducting RBC transfusion RCTs have prompted critique of their design, analyses, and interpretation. Here, we address these issues by emulating hypothetical randomized trials using large real-world data to further clarify the adverse effects of storage time. We estimated the comparative effect of transfusing exclusively older vs fresher RBC units on the primary outcome of death, and the secondary composite end point of thromboembolic events, or death, using inverse probability weighting. Thresholds were defined as 1, 2, 3, and 4 weeks of storage. A large Danish blood transfusion database from the period 2008 to 2018 comprising >900 000 transfusion events defined the observational data. A total of 89 799 patients receiving >340 000 RBC transfusions during 28 days of follow-up met the eligibility criteria. Treatment with RBC units exclusively fresher than 1, 2, 3, and 4 weeks of storage was found to decrease the 28-day recipient mortality with 2.44 percentage points (pp) (0.86 pp, 4.02 pp), 1.93 pp (0.85 pp, 3.02 pp), 1.06 pp (–0.20 pp, 2.33 pp), and −0.26 pp (–1.78 pp, 1.25 pp) compared with transfusing exclusively older RBC units, respectively. The 28-day risk differences for the composite end point were similar. This study suggests that transfusing exclusively older RBC units stored for >1 or 2 weeks increases the 28-day recipient mortality and risk of thromboembolism or death compared with transfusing fresher RBC units.

Biomarkers of Cardiac Injury, Renal Injury, and Inflammation Are Strong Mediators of Sex-Associated Death in COVID-19.

BackgroundStudies examining outcomes among individuals with COronaVIrus Disease 2019 (COVID-19) have consistently demonstrated that men have worse outcomes than women, with a higher incidence of myocardial injury, respiratory failure, and death. However, mechanisms of higher morbidity and mortality among men remain poorly understood. We aimed to identify mediators of the relationship between sex and COVID-19-associated mortality.MethodsPatients hospitalized at two quaternary care facilities, New York Presbyterian Hospital (CUIMC/NYPH) and Massachusetts General Hospital (MGH), for SARS-CoV-2 infection between February and May 2020 were included. Five independent biomarkers were identified as mediators of sex effects, including high-sensitivity cardiac troponin T (hs-cTNT), high sensitivity C-reactive protein (hs-CRP), ferritin, D-dimer, and creatinine.ResultsIn the CUIMC/NYPH cohort (n = 2,626, 43% female), male sex was associated with significantly greater mortality (26 vs. 21%, p = 0.0146) and higher peak hs-cTNT, hs-CRP, ferritin, D-dimer, and creatinine (p < 0.001). The effect of male sex on the primary outcome of death was partially mediated by peak values of all five biomarkers, suggesting that each pathophysiological pathway may contribute to increased risk of death in men. Hs-cTnT, creatinine, and hs-CRP were the strongest mediators. Findings were highly consistent in the MGH cohort with the exception of D-dimer.ConclusionsThis study suggests that the effect of sex on COVID-19 outcomes is mediated by cardiac and kidney injury, as well as underlying differences in inflammation and iron metabolism. Exploration of these specific pathways may facilitate sex-directed diagnostic and therapeutic strategies for patients with COVID-19 and provides a framework for the study of sex differences in other complex diseases.

Not By Choice: Black Patients With Advanced Heart Failure Are Less Likely To Receive A Vad Or Transplant Despite Their Preferences For Care

<h3>Introduction</h3> Heart failure (HF) disproportionately affects marginalized people, including racial and ethnic minorities, and those impacted by social determinants of health (SDoH). Inequities in access to advanced therapies are well documented, though the reasons for such inequities remain uncertain. Potential explanations include access to care, patient preference, and biases in provider decision-making. <h3>Hypothesis</h3> Race and SDoH will impact utilization of advanced therapies, and patient preference for VAD will not modify the effect. <h3>Methods</h3> We performed an observational cohort study of Black and White ambulatory chronic systolic HF patients from 21 implanting VAD centers in The Registry Evaluation for Vital Information for VADs in Ambulatory Life (REVIVAL) study. Patients had ≥1 high-risk feature for death and no contraindication to VAD at enrollment. We performed competing events cause-specific proportional hazard models using multiple imputation for missing data with the primary outcomes of (1) death or (2) durable VAD/urgent transplant (TXP). Candidate variables included demographics (race, gender, age), SDoH (education, income, insurance type, caregiver), and four time-varying variables: clinician-assessed HF severity (INTERMACS Patient Profile), patient-reported quality of life (EuroQoL Visual Analogue Scale), preference for VAD given current health (3-point Likert scale), and "want for any and all life-sustaining therapies" (yes/no). <h3>Results</h3> The study included 377 participants, of whom 100 (26.5%) identified as Black. The primary outcomes of death and VAD/TXP occurred in 14.3% (n=54) and 19.4% (n=73) of patients. Preferences for VAD and life-sustaining therapies by race were similar. There was a non-significant increase in death among Black patients (HR, 95% CI; 1.23, 0.67-2.24), while Black race (0.46, 0.24-0.87) was associated with reduced utilization of VAD/TXP (Table). Preference for VAD or general life-sustaining therapies were not associated with either death or utilization of VAD/TXP. <h3>Conclusions</h3> Among patients receiving care by advanced heart failure cardiologists at VAD centers, there is less utilization of VAD/TXP for Black patients even after adjusting for HF severity, patient-reported QOL, SDoH, and despite similar patient preferences. This residual inequity in VAD and TXP may be a consequence of structural racism or result from provider bias or racism impacting clinician decision-making.

Surfactant Delivery Without Intubation in Preterm Infants

Surfactant Delivery Without Intubation in Preterm Infants

Target Vessel Versus Complete Revascularization in Non-ST Elevation Myocardial Infarction Without Cardiogenic Shock.

IntroductionThe role of complete revascularization (CR) vs target vessel revascularization (TVR) in non-ST-elevation myocardial infarction (NSTEMI) in patients without cardiogenic shock is still not established. In this study, we compared outcomes at one and six months among patients with NSTEMI with multivessel disease (MVD) undergoing CR vs TVR.MethodsIt was a prospective, observational study carried out among 60 NSTEMI patients with MVD (30 undergoing TVR and 30 CR) from October 2018 to November 2019. They were assessed at one and six months for primary and secondary outcomes.ResultsThe mean age of the patients was 56.13 ± 9.23 years and both the groups were well matched with respect to age, gender, risk factors, and comorbidities. In the majority of patients, the target vessel was left anterior descending (LAD) followed by right coronary artery (RCA) and left circumflex (LCX) in both groups. The primary outcomes of death from any cause, non-fatal myocardial infarction, and the need for revascularization of the ischemia-driven vessel showed no significant difference at one and six months follow-up between the CR and TVR groups. However, the secondary outcomes of heart failure hospitalizations and angina episodes were significantly more in the TVR group than CR group at one month (6 vs 1, P=0.044), (8 vs 2, P=0.038) and six months (8 vs 2, P=0.038), (9 vs 2, P=0.02), respectively.ConclusionCR was associated with no difference in death from all-cause or future revascularization but significantly lesser secondary outcomes of heart failure hospitalizations and angina episodes as compared to TVR in NSTEMI without cardiogenic shock.

The response to cardiac resynchronization therapy in LMNA cardiomyopathy.

Cardiac implantable electronic device (CIED) therapy is fundamental to the management of LMNA cardiomyopathy due to the high frequency of atrioventricular block and ventricular tachyarrhythmias. We aimed to define the role of cardiac resynchronization therapy (CRT) in impacting heart failure in LMNA cardiomyopathy. From nine referral centres, LMNA cardiomyopathy patients who underwent CRT with available pre- and post-echocardiograms were identified retrospectively. Factors associated with CRT response were identified (defined as improvement in left ventricular ejection fraction [LVEF] ≥5% 6 months post-implant) and the associated impact on the primary outcome of death, implantation of a left ventricular assist device or cardiac transplantation was assessed. We identified 105 patients (mean age 51 ± 10 years) undergoing CRT, including 70 (67%) who underwent CRT as a CIED upgrade. The mean change in LVEF ∼6 months post-CRT was +4 ± 9%. A CRT response occurred in 40 (38%) patients and was associated with lower baseline LVEF or a high percentage of right ventricular pacing prior to CRT in patients with pre-existing CIED. In patients with a European Society of Cardiology class I guideline indication for CRT, response rates were 61%. A CRT response was evident at thresholds of LVEF ≤45% or percent pacing ≥50%. There was a 1.3year estimated median difference in event-free survival in those who responded to CRT (p=0.04). Systolic function improves in patients with LMNA cardiomyopathy who undergo CRT, especially with strong guideline indications for implantation. Post-CRT improvements in LVEF are associated with survival benefits in this population with otherwise limited options.