RESUMEN

BACKGROUND: We aimed to characterise the variation in access to and outcomes of cardiac surgery for people in England. METHODS: We included people >18 years of age with hospital admission for ischaemic heart disease (IHD) and heart valve disease (HVD) between 2010 and 2019. Within these populations, we identified people who had coronary artery bypass graft (CABG) and/or valve surgery, respectively. We fitted logistic regression models to examine the effects of age, sex, ethnicity and socioeconomic deprivation on having access to surgery and in-hospital mortality, 1-year mortality and hospital readmission. RESULTS: We included 292 140 people, of whom 28% were women, 11% were from an ethnic minority and 17% were from the most deprived areas. Across all types of surgery, one in five people are readmitted to hospital within 1 year, rising to almost one in four for valve surgery. Women, black people and people living in the most deprived areas were less likely to have access to surgery (CABG: 59%, 32% and 35% less likely; valve: 31%, 33% and 39% less likely, respectively) and more likely to die within 1 year of surgery (CABG: 24%, 85% and 18% more likely, respectively; valve: 19% (women) and 10% (people from most deprived areas) more likely). CONCLUSIONS: Female sex, black ethnicity and economic deprivation are independently associated with limited access to cardiac surgery and higher post-surgery mortality. Actions are required to address these inequalities.

RESUMEN

OBJECTIVES: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery and affects around 30% of patients. Variable guidelines from multiple organizations exist for the prevention of POAF after cardiac surgery. A survey of UK practice was conducted to define "usual care" for a platform trial of interventions to prevent POAF after cardiac surgery. To provide context for the survey, all current guidelines for the prevention and management of atrial fibrillation (AF) after cardiac surgery were reviewed. DESIGN: Online survey and literature review. SETTING: All 35 UK National Health Service Cardiac Surgery Centres participated in the survey. Guidelines from specialist societies and other guideline-making organizations from the UK, Europe, and North America were reviewed. PARTICIPANTS: Established a link network of researchers. MEASUREMENTS AND MAIN RESULTS: Five relevant guidelines were identified from the literature review. All guidelines recommend ß-blockade for prevention of AF after cardiac surgery. Treatment of AF is recommended using either rate or rhythm control. Cardioversion is recommended only for the hemodynamically unstable patient. Patients who remain in AF for over 48 hours should be considered for anticoagulation. Patients should be followed up within 60 days to review the need for antiarrhythmic and anticoagulant therapy. Of 35 centers, 31 (89%) responded. A total of 11 of 31 (35.5%) centers followed local guidance for prevention of POAF, 4 (13%) centers followed Society of Cardiovascular Anesthesiologists/European Association of Cardiothoracic Anaesthesia guidelines, 4 (13%) followed UK National Institute of Health and Care Excellence guidance and 4 followed "other" guidance. Of 31 centers, 8 (26%) followed no guidelines to prevent POAF; 28 of 31 (90%) centers did not risk-stratify their patients for POAF. Most centers (23/31, 74%) did not have a care package in place to prevent POAF, but 14 of 31 (45%) try in some way to prevent AF in patients presenting with sinus rhythm. The most common interventions to prevent POAF are ß-blocker use postoperatively (23/31, 74%), magnesium (20/31, 64.5%), and maintaining a serum K+ ≥4.5 mmol/L (26/31, 84%). CONCLUSIONS: Guidance to prevent AF after cardiac surgery centers around the use of ß-blockade. Although patients in the UK do not appear to be risk-assessed for POAF, the main interventions used to prevent it are similar: ß-blockade and maintenance of serum K+ and Mg2+ levels.

Asunto(s)

Fibrilación Atrial , Procedimientos Quirúrgicos Cardíacos , Complicaciones Posoperatorias , Guías de Práctica Clínica como Asunto , Fibrilación Atrial/prevención & control , Fibrilación Atrial/etiología , Humanos , Reino Unido/epidemiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología

RESUMEN

Acute kidney injury (AKI) affects 10-15% of hospitalised patients and arises after severe infections, major surgeries, or exposure to nephrotoxic drugs. AKI diagnosis based on creatinine level changes lacks specificity and may be delayed. MicroRNAs are short non-coding RNA secreted by all cells. This review of studies measuring miRNAs in AKI aimed to verify miRNAs as diagnostic markers. The study included data from patients diagnosed with AKI due to sepsis, ischaemia, nephrotoxins, radiocontrast, shock, trauma, and cardiopulmonary bypass. Out of 71 studies, the majority focused on AKI in sepsis patients, followed by cardiac surgery patients, ICU patients, and individuals receiving nephrotoxic agents or experiencing ischaemia. Studies that used untargeted assays found 856 differentially regulated miRNAs, although none of these were confirmed by more than one study. Moreover, 68 studies measured miRNAs by qRT-PCR, and 2 studies reported downregulation of miR-495-3p and miR-370-3p in AKI patients with sepsis after the AKI diagnosis. In three studies, upregulation of miR-21 was reported at the time of the AKI diagnosis with a significant pooled effect of 0.56. MiR-21 was also measured 19-24 h after cardiac surgery in three studies. However, the pooled effect was not significant. Despite the considerable research into miRNA in AKI, there is a knowledge gap in their applicability as diagnostic markers of AKI in humans.

RESUMEN

OBJECTIVES: Myocardial revascularisation and cardiopulmonary bypass (CPB) can cause ischaemia-reperfusion injury, leading to myocardial and other end-organ damage. Volatile anaesthetics protect the myocardium in experimental studies. However, there is uncertainty about whether this translates into clinical benefits because of the coadministration of propofol and its detrimental effects, restricting myocardial protective processes. METHODS: In this single-blinded, parallel-group randomised controlled feasibility trial, higher-risk patients undergoing elective coronary artery bypass graft (CABG) surgery with an additive European System for Cardiac Operative Risk Evaluation ≥5 were randomised to receive either propofol or total inhalational anaesthesia as single agents for maintenance of anaesthesia. The primary outcome was the feasibility of recruiting and randomising 50 patients across two cardiac surgical centres, and secondary outcomes included the feasibility of collecting the planned perioperative data, clinically relevant outcomes and assessments of effective patient identification, screening and recruitment. RESULTS: All 50 patients were recruited within 11 months in two centres, allowing for a 13-month hiatus in recruitment due to the COVID-19 pandemic. Overall, 50/108 (46%) of eligible patients were recruited. One patient withdrew before surgery and one patient did not undergo surgery. All but one completed in-hospital and 30-day follow-up. CONCLUSIONS: It is feasible to recruit and randomise higher-risk patients undergoing CABG surgery to a study comparing total inhalational and propofol anaesthesia in a timely manner and with high acceptance and completion rates. TRIAL REGISTRATION NUMBER: NCT04039854.

Asunto(s)

Anestésicos Intravenosos , Puente de Arteria Coronaria , Estudios de Factibilidad , Propofol , Humanos , Propofol/administración & dosificación , Propofol/efectos adversos , Masculino , Femenino , Proyectos Piloto , Anciano , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/efectos adversos , Persona de Mediana Edad , Método Simple Ciego , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/métodos , Anestesia por Inhalación/métodos , Anestesia por Inhalación/efectos adversos , Resultado del Tratamiento , Medición de Riesgo/métodos , Factores de Riesgo , COVID-19/epidemiología , COVID-19/prevención & control , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Anestésicos por Inhalación/administración & dosificación , Anestésicos por Inhalación/efectos adversos , Puente Cardiopulmonar/efectos adversos , Puente Cardiopulmonar/métodos

RESUMEN

BACKGROUND: Aortic valve replacement in asymptomatic severe aortic stenosis is controversial. The Early valve replacement in severe ASYmptomatic Aortic Stenosis (EASY-AS) trial aims to determine whether early aortic valve replacement improves clinical outcomes, quality of life and cost-effectiveness compared to a guideline recommended strategy of 'watchful waiting'. METHODS: In a pragmatic international, open parallel group randomized controlled trial (NCT04204915), 2844 patients with severe aortic stenosis will be randomized 1:1 to either a strategy of early (surgical or transcatheter) aortic valve replacement or aortic valve replacement only if symptoms or impaired left ventricular function develop, or other cardiac surgery becomes nessessary. Exclusion criteria include other severe valvular disease, planned cardiac surgery, ejection fraction <50%, previous aortic valve replacement or life expectancy <2 years. The primary outcome is a composite of cardiovascular mortality or heart failure hospitalization. The primary analysis will be undertaken when 663 primary events have accrued, providing 90% power to detect a reduction in the primary endpoint from 27.7% to 21.6% (hazard ratio 0.75). Secondary endpoints include disability-free survival, days alive and out of hospital, major adverse cardiovascular events and quality of life. RESULTS: Recruitment commenced in March 2020 and is open in the UK, Australia, New Zealand, and Serbia. Feasibility requirements were met in July 2022, and the main phase opened in October 2022, with additional international centers in set-up. CONCLUSIONS: The EASY-AS trial will establish whether a strategy of early aortic valve replacement in asymptomatic patients with severe aortic stenosis reduces cardiovascular mortality or heart failure hospitalization and improves other important outcomes.

Asunto(s)

Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Calidad de Vida , Humanos , Estenosis de la Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Enfermedades Asintomáticas , Índice de Severidad de la Enfermedad , Análisis Costo-Beneficio , Válvula Aórtica/cirugía , Masculino , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Femenino

RESUMEN

Unfractionated heparin (UFH) is an effective antithrombotic during surgery but has known adverse effects, in particular on platelets. A marked increase in platelet responsiveness has previously been observed in patients within minutes of receiving UFH, despite adequate inhibition by aspirin prior to heparin. We studied this phenomenon in patients undergoing cardiac artery bypass grafting (n = 17) to determine whether the effects of heparin were systemic or platelet-specific. All patients' platelets were fully inhibited by aspirin prior to surgery, but within 3 min of receiving heparin spontaneous aggregation and responses to arachidonic acid (AA) and ADP increased significantly (p ≥ 0.0002), and activated platelets were found in the circulation. While there was no rise in thromboxane in the plasma following heparin, levels of the major platelet 12-lipoxygenase product, 12-HETE, rose significantly. Mixing experiments demonstrated that the changes caused by heparin resided primarily in the platelets, while addition of AA pathway inhibitors, and analysis of oxylipins provided evidence that, following heparin, aggregating platelets regained their ability to synthesise thromboxane. These findings highlight potentially unrecognised pro-thrombotic and pro-inflammatory changes during CABG surgery, and provide further evidence of adverse effects associated with UFH.

Asunto(s)

Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Heparina , Humanos , Heparina/farmacología , Ácido Araquidónico , Aspirina/farmacología , Puente de Arteria Coronaria , Tromboxanos

RESUMEN

BACKGROUND: Cardiac surgery triggers a strong inflammatory reaction, which carries significant clinical consequences. Corticosteroids have been suggested as a potential perioperative strategy to reduce inflammation and help prevent postoperative complications. However, the safety and effectiveness of perioperative corticosteroid use in adult cardiac surgery is uncertain. This is an update of the 2011 review with 18 studies added. OBJECTIVES: Primary objective: to estimate the effects of prophylactic corticosteroid use in adults undergoing cardiac surgery with cardiopulmonary bypass on the: - co-primary endpoints of mortality, myocardial complications, and pulmonary complications; and - secondary outcomes including atrial fibrillation, infection, organ injury, known complications of steroid therapy, prolonged mechanical ventilation, prolonged postoperative stay, and cost-effectiveness. SECONDARY OBJECTIVE: to explore the role of characteristics of the study cohort and specific features of the intervention in determining the treatment effects via a series of prespecified subgroup analyses. SEARCH METHODS: We used standard, extensive Cochrane search methods to identify randomised studies assessing the effect of corticosteroids in adult cardiac surgery. The latest searches were performed on 14 October 2022. SELECTION CRITERIA: We included randomised controlled trials in adults (over 18 years, either with a diagnosis of coronary artery disease or cardiac valve disease, or who were candidates for cardiac surgery with the use of cardiopulmonary bypass), comparing corticosteroids with no treatments. There were no restrictions with respect to length of the follow-up period. All selected studies qualified for pooling of results for one or more endpoints. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, and cardiac and pulmonary complications. Secondary outcomes were infectious complications, gastrointestinal bleeding, occurrence of new post-surgery atrial fibrillation, re-thoracotomy for bleeding, neurological complications, renal failure, inotropic support, postoperative bleeding, mechanical ventilation time, length of stays in the intensive care unit (ICU) and hospital, patient quality of life, and cost-effectiveness. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: This updated review includes 72 randomised trials with 17,282 participants (all 72 trials with 16,962 participants were included in data synthesis). Four trials (6%) were considered at low risk of bias in all the domains. The median age of participants included in the studies was 62.9 years. Study populations consisted mainly (89%) of low-risk, first-time coronary artery bypass grafting (CABG) or valve surgery. The use of perioperative corticosteroids may result in little to no difference in all-cause mortality (risk with corticosteroids: 25 to 36 per 1000 versus 33 per 1000 with placebo or no treatment; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.75 to 1.07; 25 studies, 14,940 participants; low-certainty evidence). Corticosteroids may increase the risk of myocardial complications (68 to 86 per 1000) compared with placebo or no treatment (66 per 1000; RR 1.16, 95% CI 1.04 to 1.31; 25 studies, 14,766 participants; low-certainty evidence), and may reduce the risk of pulmonary complications (risk with corticosteroids: 61 to 77 per 1000 versus 78 per 1000 with placebo/no treatment; RR 0.88, 0.78 to 0.99; 18 studies, 13,549 participants; low-certainty evidence). Analyses of secondary endpoints showed that corticosteroids may reduce the incidence of infectious complications (risk with corticosteroids: 94 to 113 per 1000 versus 123 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.76 to 0.92; 28 studies, 14,771 participants; low-certainty evidence). Corticosteroids may result in little to no difference in incidence of gastrointestinal bleeding (risk with corticosteroids: 9 to 17 per 1000 versus 10 per 1000 with placebo/no treatment; RR 1.21, 95% CI 0.87 to 1.67; 6 studies, 12,533 participants; low-certainty evidence) and renal failure (risk with corticosteroids: 23 to 35 per 1000 versus 34 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.69 to 1.02; 13 studies, 12,799; low-certainty evidence). Corticosteroids may reduce the length of hospital stay, but the evidence is very uncertain (-0.5 days, 0.97 to 0.04 fewer days of length of hospital stay compared with placebo/no treatment; 25 studies, 1841 participants; very low-certainty evidence). The results from the two largest trials included in the review possibly skew the overall findings from the meta-analysis. AUTHORS' CONCLUSIONS: A systematic review of trials evaluating the organ protective effects of corticosteroids in cardiac surgery demonstrated little or no treatment effect on mortality, gastrointestinal bleeding, and renal failure. There were opposing treatment effects on cardiac and pulmonary complications, with evidence that corticosteroids may increase cardiac complications but reduce pulmonary complications; however, the level of certainty for these estimates was low. There were minor benefits from corticosteroid therapy for infectious complications, but the evidence on hospital length of stay was very uncertain. The inconsistent treatment effects across different outcomes and the limited data on high-risk groups reduced the applicability of the findings. Further research should explore the role of these drugs in specific, vulnerable cohorts.

Asunto(s)

Corticoesteroides , Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Complicaciones Posoperatorias , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Puente Cardiopulmonar/efectos adversos , Puente Cardiopulmonar/mortalidad , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/mortalidad , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/mortalidad , Corticoesteroides/uso terapéutico , Corticoesteroides/efectos adversos , Sesgo , Adulto , Tiempo de Internación , Causas de Muerte , Fibrilación Atrial/prevención & control , Fibrilación Atrial/mortalidad , Enfermedades de las Válvulas Cardíacas/cirugía , Enfermedades de las Válvulas Cardíacas/mortalidad , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/mortalidad , Respiración Artificial/efectos adversos , Respiración Artificial/estadística & datos numéricos , Persona de Mediana Edad

RESUMEN

AIM: We aimed to review all randomised controlled trial (RCT) data to explore optimal identification and treatment strategies of frail patients with Acute Coronary Syndromes (ACS). METHODS: The protocol was preregistered (PROSPERO - CRD42021250235). We performed a systematic review including RCT's that 1; used at least one frailty assessment tool to assess frailty and its impact on outcomes in patients diagnosed with ACS and 2; used at least one intervention where change in frailty was measured in patients diagnosed with ACS. The Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE were searched on the 1st April 2021 and updated on 4th July 2023. Owing to low search output results are presented as a narrative synthesis of available evidence. RESULTS: A single RCT used a frailty assessment tool. A single RCT specifically targeted frailty with their intervention. This precluded further quantitative analysis. There was indication of selection bias against frail participants, and a signal of value for physical activity measurement in frail ACS patients. There was a high level of uncertainty and low level of robustness of this evidence. CONCLUSIONS: Data from RCT's alone is inadequate in answering the reviews question. Future RCT's need to address ways to incorporate frail participants, whilst mitigating selection biases. Physical performance aspects of the frailty syndrome appear to be high yield modifiable targets that improve outcomes. Intervention trials should consider using change in frailty status as an outcome measure. Any trials that include frail participants should present data specifically attributable to this group.

Asunto(s)

Síndrome Coronario Agudo , Fragilidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Síndrome Coronario Agudo/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Fragilidad/diagnóstico , Anciano Frágil , Anciano , Evaluación Geriátrica/métodos

RESUMEN

In an era focused on value-based healthcare, the quality of healthcare and resource allocation should be underpinned by empirical evidence. Pragmatic clinical trials (pRCTs) are essential in this endeavor, providing randomized controlled trial (RCT) insights that encapsulate real-world effects of interventions. The rising popularity of pRCTs can be attributed to their ability to mirror real-world practices, accommodate larger sample sizes, and provide cost advantages over traditional RCTs. By harmonizing efficacy with effectiveness, pRCTs assist decision-makers in prioritizing interventions that have a substantial public health impact and align with the tenets of value-based health care. An international network for pRCT provides several advantages, including larger and diverse patient populations, access to a broader range of healthcare settings, sharing knowledge and expertise, and overcoming ethical and regulatory barriers. The hypothesis and study design of pRCT answers the decision-maker's questions. pRCT compares clinically relevant alternative interventions, recruits participants from diverse practice settings, and collects data on various health outcomes. They are scarce because the medical products industry typically does not fund pRCT. Prioritizing these studies by expanding the infrastructure to conduct clinical research within the healthcare delivery system and increasing public and private funding for these studies will be necessary to facilitate pRCTs. These changes require more clinical and health policy decision-makers in clinical research priority setting, infrastructure development, and funding. This paper presents a comprehensive overview of pRCTs, emphasizing their importance in evidence-based medicine and the advantages of an international collaborative network for their execution. It details the development of PRIME-9, an international initiative across nine countries to advance pRCTs, and explores various statistical approaches for these trials. The paper underscores the need to overcome current challenges, such as funding limitations and infrastructural constraints, to leverage the full potential of pRCTs in optimizing healthcare quality and resource utilization.

Asunto(s)

Personal Administrativo , Proyectos de Investigación , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Tamaño de la Muestra , Medicina Basada en la Evidencia

RESUMEN

BACKGROUND: There is limited report of outcomes in women undergoing isolated coronary artery bypass grafting (CABG) with left internal thoracic artery and different second conduits (saphenous vein graft [SVG], radial artery [RA], and right internal thoracic artery [RITA]). METHODS: The National Adult Cardiac Surgery Audit database was queried for women undergoing isolated CABG with left internal thoracic artery graft in the United Kingdom from 1996 to 2019. Propensity score-based pairwise comparisons were performed between graft types. The primary outcome was in-hospital mortality. RESULTS: The study included 58,063 women (SVG, n = 48,881 [84.2%]; RA, n = 6136 [10.6%]; RITA, n = 2445 [4.2%]). SVG use was stable over the years; RA and RITA use decreased. In-hospital mortality was similar between the RA and RITA grafts (2.3% vs 2.8%; odds ratio [OR], 0.80; 95% CI, 0.53-1.22; P = .39) and between the RA and SVG (2.3% vs 2.0%; OR, 1.20; 95% CI, 0.93-1.55; P = .17) but higher in the RITA group compared with the SVG (2.7% vs 1.4%; OR, 2.04; 95% CI, 1.27-3.36; P = .004). Women receiving the RITA graft were more likely to have sternal wound infection (SWI) compared with the RA (0.6% vs 0.06%; P = .004) and the SVG (0.6% vs 0.2%; P = .032). SWI was consistently associated with higher risk of in-hospital mortality. CONCLUSIONS: Conduit selection may affect operative outcomes in women undergoing CABG. The RA shows similar mortality and risk of deep SWI as the SVG.

Asunto(s)

Enfermedad de la Arteria Coronaria , Arterias Mamarias , Adulto , Humanos , Femenino , Resultado del Tratamiento , Estudios Retrospectivos , Puente de Arteria Coronaria , Arterias Mamarias/trasplante , Reino Unido/epidemiología , Arteria Radial/trasplante , Vena Safena/trasplante , Enfermedad de la Arteria Coronaria/cirugía

RESUMEN

BACKGROUND: Osteopontin has been implicated in vascular calcification formation and vein graft intimal hyperplasia, and its expression can be triggered by pro-inflammatory activation of cells. The role of osteopontin and the temporal formation of microcalcification in vein grafts is poorly understood with a lack of understanding of the interaction between haemodynamic changes and the activation of osteopontin. METHODS: We used a porcine model of vein interposition grafts, and human long saphenous veins exposed to ex vivo perfusion, to study the activation of osteopontin using polymerase chain reaction, immunostaining, and 18F-sodium fluoride autoradiography. RESULTS: The porcine model showed that osteopontin is active in grafts within 1 week following surgery and demonstrated the presence of microcalcification. A brief pretreatment of long saphenous veins with dexamethasone can suppress osteopontin activation. Prolonged culture of veins after exposure to acute arterial haemodynamics resulted in the formation of microcalcification but this was suppressed by pretreatment with dexamethasone. 18F-sodium fluoride uptake was significantly increased as early as 1 week in both models, and the pretreatment of long saphenous veins with dexamethasone was able to abolish its uptake. CONCLUSIONS: Osteopontin is activated in vein grafts and is associated with microcalcification formation. A brief pretreatment of veins ex vivo with dexamethasone can suppress its activation and associated microcalcification.

Asunto(s)

Calcinosis , Osteopontina , Humanos , Porcinos , Animales , Osteopontina/metabolismo , Fluoruro de Sodio , Vena Safena/trasplante , Dexametasona/farmacología , Calcinosis/metabolismo

RESUMEN

BACKGROUND: Organ injury is a common and severe complication of cardiac surgery that contributes to the majority of deaths. There are no effective treatment or prevention strategies. It has been suggested that innate immune system activation may have a causal role in organ injury. A wide range of organ protection interventions targeting the innate immune response have been evaluated in randomised controlled trials (RCTs) in adult cardiac surgery patients, with inconsistent results in terms of effectiveness. OBJECTIVES: The aim of the review was to summarise the results of RCTs of organ protection interventions targeting the innate immune response in adult cardiac surgery. The review considered whether the interventions had a treatment effect on inflammation, important clinical outcomes, or both. SEARCH METHODS: CENTRAL, MEDLINE, Embase, conference proceedings and two trial registers were searched on October 2022 together with reference checking to identify additional studies. SELECTION CRITERIA: RCTs comparing organ protection interventions targeting the innate immune response versus placebo or no treatment in adult patients undergoing cardiac surgery where the treatment effect on innate immune activation and on clinical outcomes of interest were reported. DATA COLLECTION AND ANALYSIS: Searches, study selection, quality assessment, and data extractions were performed independently by pairs of authors. The primary inflammation outcomes were peak IL-6 and IL-8 concentrations in blood post-surgery. The primary clinical outcome was in-hospital or 30-day mortality. Treatment effects were expressed as risk ratios (RR) and standardised mean difference (SMD) with 95% confidence intervals (CI). Meta-analyses were performed using random effects models, and heterogeneity was assessed using I2. MAIN RESULTS: A total of 40,255 participants from 328 RCTs were included in the synthesis. The effects of treatments on IL-6 (SMD -0.77, 95% CI -0.97 to -0.58, I2 = 92%) and IL-8 (SMD -0.92, 95% CI -1.20 to -0.65, I2 = 91%) were unclear due to heterogeneity. Heterogeneity for inflammation outcomes persisted across multiple sensitivity and moderator analyses. The pooled treatment effect for in-hospital or 30-day mortality was RR 0.78, 95% CI 0.68 to 0.91, I2 = 0%, suggesting a significant clinical benefit. There was little or no treatment effect on mortality when analyses were restricted to studies at low risk of bias. Post hoc analyses failed to demonstrate consistent treatment effects on inflammation and clinical outcomes. Levels of certainty for pooled treatment effects on the primary outcomes were very low. AUTHORS' CONCLUSIONS: A systematic review of RCTs of organ protection interventions targeting innate immune system activation did not resolve uncertainty as to the effectiveness of these treatments, or the role of innate immunity in organ injury following cardiac surgery.

Asunto(s)

Procedimientos Quirúrgicos Cardíacos , Interleucina-6 , Humanos , Adulto , Interleucina-8 , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Inflamación , Síndrome de Respuesta Inflamatoria Sistémica

RESUMEN

BACKGROUND: In-centre nocturnal haemodialysis (INHD) offers extended-hours haemodialysis, 6 to 8 h thrice-weekly overnight, with the support of dialysis specialist nurses. There is increasing observational data demonstrating potential benefits of INHD on health-related quality of life (HRQoL). There is a lack of randomised controlled trial (RCT) data to confirm these benefits and assess safety. METHODS: The NightLife study is a pragmatic, two-arm, multicentre RCT comparing the impact of 6 months INHD to conventional haemodialysis (thrice-weekly daytime in-centre haemodialysis, 3.5-5 h per session). The primary outcome is the total score from the Kidney Disease Quality of Life tool at 6 months. Secondary outcomes include sleep and cognitive function, measures of safety, adherence to dialysis and impact on clinical parameters. There is an embedded Process Evaluation to assess implementation, health economic modelling and a QuinteT Recruitment Intervention to understand factors that influence recruitment and retention. Adults (≥ 18 years old) who have been established on haemodialysis for > 3 months are eligible to participate. DISCUSSION: There are 68,000 adults in the UK that need kidney replacement therapy (KRT), with in-centre haemodialysis the treatment modality for over a third of cases. HRQoL is an independent predictor of hospitalisation and mortality in individuals on maintenance dialysis. Haemodialysis is associated with poor HRQoL in comparison to the general population. INHD has the potential to improve HRQoL. Vigorous RCT evidence of effectiveness is lacking. The NightLife study is an essential step in the understanding of dialysis therapies and will guide patient-centred decisions regarding KRT in the future. TRIAL REGISTRATION: Trial registration number: ISRCTN87042063. Registered: 14/07/2020.

Asunto(s)

Diálisis Renal , Terapia de Reemplazo Renal , Adulto , Humanos , Adolescente , Análisis Costo-Beneficio , Diálisis Renal/efectos adversos , Diálisis Renal/métodos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

INTRODUCTION: Congenital heart disease (CHD) represents the most common birth defect, affecting from 0.4% to 1.2% of children born in developed countries. The survival of these patients has increased significantly, but CHD remains one of the major causes of neonatal and childhood death. The aetiology of CHD is complex, with some evidence of both genetic and environmental causes. However, there is still lack of knowledge regarding modifiable risk factors and molecular and genetic mechanisms underlying the development of CHD. This study aims to develop a prospective cohort of patients undergoing cardiac procedures that will bring together routinely collected clinical data and biological samples from patients and their biological mothers, in order to investigate risk factors and predictors of postoperative-outcomes, as well as better understanding the effect of the surgical intervention on the early and long-term outcomes. METHODS AND ANALYSIS: Children OMACp (OMACp, outcome monitoring after cardiac procedure in congenital heart disease) is a multicentre, prospective cohort study recruiting children with CHD undergoing a cardiac procedure. The study aims to recruit 3000 participants over 5 years (2019-2024) across multiple UK sites. Routine clinical data will be collected, as well as participant questionnaires collecting sociodemographic, NHS resource use and quality of life data. Biological samples (blood, urine and surgical waste tissue from patients, and blood and urine samples from biological mothers) will be collected where consent has been obtained. Follow-up outcome and questionnaire data will be collected for 5 years. ETHICS AND DISSEMINATION: The study was approved by the London-Brent Research Ethics Committee on 30 July 2019 (19/SW/0113). Participants (or their parent/guardian if under 16 years of age) must provide informed consent prior to being recruited into the study. Mothers who wish to take part must also provide informed consent prior to being recruited. The study is sponsored by University Hospitals Bristol and Weston Foundation Trust and is managed by the University of Bristol. Children OMACp is adopted onto the National Institute for Health Research Clinical Research Network portfolio. Findings will be disseminated through peer-reviewed publications, presentation at conference, meetings and through patient organisations and newsletters. TRIAL REGISTRATION NUMBER: ISRCTN17650644.

Asunto(s)

Cardiopatías Congénitas , Calidad de Vida , Recién Nacido , Embarazo , Femenino , Humanos , Lactante , Niño , Adulto Joven , Estudios Prospectivos , Parto , Cardiopatías Congénitas/cirugía , Medición de Riesgo , Estudios Multicéntricos como Asunto

RESUMEN

Importance: The safety and effectiveness of mitral valve repair via thoracoscopically-guided minithoracotomy (minithoracotomy) compared with median sternotomy (sternotomy) in patients with degenerative mitral valve regurgitation is uncertain. Objective: To compare the safety and effectiveness of minithoracotomy vs sternotomy mitral valve repair in a randomized trial. Design, Setting, and Participants: A pragmatic, multicenter, superiority, randomized clinical trial in 10 tertiary care institutions in the UK. Participants were adults with degenerative mitral regurgitation undergoing mitral valve repair surgery. Interventions: Participants were randomized 1:1 with concealed allocation to receive either minithoracotomy or sternotomy mitral valve repair performed by an expert surgeon. Main Outcomes and Measures: The primary outcome was physical functioning and associated return to usual activities measured by change from baseline in the 36-Item Short Form Health Survey (SF-36) version 2 physical functioning scale 12 weeks after the index surgery, assessed by an independent researcher masked to the intervention. Secondary outcomes included recurrent mitral regurgitation grade, physical activity, and quality of life. The prespecified safety outcomes included death, repeat mitral valve surgery, or heart failure hospitalization up to 1 year. Results: Between November 2016 and January 2021, 330 participants were randomized (mean age, 67 years, 100 female [30%]); 166 were allocated to minithoracotomy and 164 allocated to sternotomy, of whom 309 underwent surgery and 294 reported the primary outcome. At 12 weeks, the mean between-group difference in the change in the SF-36 physical function T score was 0.68 (95% CI, -1.89 to 3.26). Valve repair rates (≈ 96%) were similar in both groups. Echocardiography demonstrated mitral regurgitation severity as none or mild for 92% of participants at 1 year with no difference between groups. The composite safety outcome occurred in 5.4% (9 of 166) of patients undergoing minithoracotomy and 6.1% (10 of 163) undergoing sternotomy at 1 year. Conclusions and relevance: Minithoracotomy is not superior to sternotomy in recovery of physical function at 12 weeks. Minithoracotomy achieves high rates and quality of valve repair and has similar safety outcomes at 1 year to sternotomy. The results provide evidence to inform shared decision-making and treatment guidelines. Trial Registration: isrctn.org Identifier: ISRCTN13930454.

Asunto(s)

Procedimientos Quirúrgicos Cardíacos , Insuficiencia de la Válvula Mitral , Esternotomía , Toracotomía , Anciano , Femenino , Humanos , Procedimientos Quirúrgicos Cardíacos/métodos , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/cirugía , Calidad de Vida , Esternotomía/métodos , Toracotomía/métodos , Resultado del Tratamiento , Toracoscopía/métodos , Masculino , Recuperación de la Función

RESUMEN

The long saphenous vein is the most used conduit in cardiac surgery, but its long-term patency is limited by vein graft disease (VGD). Endothelial dysfunction is a key driver of VGD; its aetiology is multi-factorial. However emerging evidence identifies vein conduit harvest technique and preservation fluids as causal in their onset and propagation. This study aims to comprehensively review published data on the relationship between preservation solutions, endothelial cell integrity and function, and VGD in human saphenous veins harvested for CABG. The review was registered with PROSPERO (CRD42022358828). Electronic searches of Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were undertaken from inception until August 2022. Papers were evaluated in line with registered inclusion and exclusion criteria. Searches identified 13 prospective, controlled studies for inclusion in the analysis. All studies used saline as a control solution. Intervention solutions included heparinised whole blood and saline, DuraGraft, TiProtec, EuroCollins, University of Wisconsin (UoW), buffered, cardioplegic and Pyruvate solutions. Most studies demonstrated that normal saline appears to have negative effects on venous endothelium and the most effective preservation solutions identified in this review were TiProtec and DuraGraft. The most used preservation solutions in the UK are heparinised saline or autologous whole blood. There is substantial heterogeneity both in practice and reporting of trials evaluating vein graft preservation solutions, and the quality of existing evidence is low. There is an unmet need for high quality trials evaluating the potential for these interventions to improve long-term patency in venous bypass grafts.

Asunto(s)

Soluciones Preservantes de Órganos , Enfermedades Vasculares , Humanos , Vena Safena/trasplante , Estudios Prospectivos , Endotelio Vascular , Reino Unido

RESUMEN

AIMS: The choice of revascularization with coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) in people with ischaemic left ventricular dysfunction is not guided by high-quality evidence. METHODS AND RESULTS: A trial of CABG vs. PCI in people with heart failure (HF) was modelled in silico using routinely collected healthcare data. The in silico trial cohort was selected by matching the target trial cohort, identified from Hospital Episode Statistics in England, with individual patient data from the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Allocation to CABG vs. complex PCI demonstrated random variation across administrative regions in England and was a valid statistical instrument. The primary outcome was 5-year all-cause mortality or cardiovascular hospitalization. Instrumental variable analysis (IVA) was used for the primary analysis. Results were expressed as average treatment effects (ATEs) with 95 confidence intervals (CIs). The target population included 13 519 HF patients undergoing CABG or complex PCI between April 2009 and March 2015. After matching, the emulated trial cohort included 2046 patients. The unadjusted primary outcome rate was 51.1 in the CABG group and 70.0 in the PCI group. IVA of the emulated cohort showed that CABG was associated with a lower risk of the primary outcome (ATE 16.2, 95 CI 20.6 to 11.8), with comparable estimates in the unmatched target population (ATE 15.5, 95 CI 17.5 to 13.5). CONCLUSION: In people with HF, in silico modelling suggests that CABG is associated with fewer deaths or cardiovascular hospitalizations at 5 years vs. complex PCI. A pragmatic clinical trial is needed to test this hypothesis and this trial would be feasible.

Asunto(s)

Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/métodos , Datos de Salud Recolectados Rutinariamente , Puente de Arteria Coronaria/métodos , Insuficiencia Cardíaca/cirugía , Insuficiencia Cardíaca/complicaciones , Simulación por Computador , Resultado del Tratamiento , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/cirugía

RESUMEN

AIMS: Standardized data definitions are necessary for the quantification of quality of care and patient outcomes in observational studies and randomised controlled trials (RCTs). The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology (ESC) aims to create pan-European data standards for cardiovascular diseases and interventions, including transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: We followed the EuroHeart methodology for cardiovascular data standard development. A Working Group of 29 members representing 12 countries was established and included a patient representative, as well as experts in the management of valvular heart disease from the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Association of Cardiovascular Imaging (EACVI) and the Working Group on Cardiovascular Surgery. We conducted a systematic review of the literature and used a modified Delphi method to reach consensus on a final set of variables. For each variable, the Working Group provided a definition, permissible values, and categorized the variable as mandatory (Level 1) or additional (Level 2) based on its clinical importance and feasibility. In total, 93 Level 1 and 113 Level 2 variables were selected, with the level 1 variables providing the dataset for registration of patients undergoing TAVI on the EuroHeart IT platform. CONCLUSION: This document provides details of the EuroHeart data standards for TAVI processes of care and in-hospital outcomes. In the context of EuroHeart, this will facilitate quality improvement, observational research, registry-based RCTs and post-marketing surveillance of devices, and pharmacotherapies. ONE-SENTENCE SUMMARY: The EuroHeart data standards for transcatheter aortic valve implantation (TAVI) are a set of internationally agreed data variables and definitions that once implemented will facilitate improvement of quality of care and outcomes for patients receiving TAVI.

Asunto(s)

Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Sistema de Registros , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

OBJECTIVE: This study aimed to systematically review the effects of declared and undeclared conflicts of interest on randomised controlled trials (RCTs) of patient blood management (PBM) interventions. DESIGN: We performed a secondary analysis of a recently published meta-analysis of RCTs evaluating five common PBM interventions in patients undergoing major surgery. DATA SOURCES: The databases searched by the original systematic reviews were searched using subject headings and Medical Subject Headings terms according to search strategies from the final search time-points until 1 June 2019. ELIGIBILITY CRITERIA: RCTs on PBM irrespective of blinding, language, date of publication and sample size were included. Abstracts and unpublished trials were excluded. Conflicts of interest were defined as sponsorship, funding or authorship by industry, professional PBM advocacy groups or blood services. DATA EXTRACTION AND SYNTHESIS: Three independent reviewers extracted the data and assessed the risk of bias. Pooled treatment effect estimates were reported as risk ratios (RRs) or standardised mean difference with 95% CIs. Heterogeneity was quantified using the I2 statistic. RESULTS: Three hundred and eighty-nine RCTs totalling 53 635 participants were included. Thirty-two trials (8%) were considered free from important sources of bias. There was reporting bias favouring PBM interventions on transfusion across all analyses. In trials with no declared author conflicts of interest, the treatment effect on mortality was RR 1.12 (0.86 to 1.45). In trials where author conflicts of interest were declared, the treatment effect on mortality was RR 0.84 (0.69 to 1.03), with significant reporting bias favouring PBM interventions. Trials with declared conflicts linked to professional PBM advocacy groups (five studies, n=977 patients) reported statistically significant reductions in mortality RR 0.40 (0.17 to 0.92), unlike other groups. CONCLUSIONS: Low certainty of the evidence that guides PBM implementation is confounded by evidence of reporting bias, and the effects of declared and undeclared conflicts of interest, favouring PBM on important trial outcomes.

Asunto(s)

Conflicto de Intereses , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

We hypothesised that measuring changes in urinary levels of EV and miR will predict the onset of acute kidney injury in cardiac surgery patients. The study was performed in the cohort of the REVAKI-2 trial. Urine samples were collected before and 24 h after the procedure from 94 cardiac surgery patients. Urinary particle concentrations and size distribution were assessed using NanoSight. EV derivation and levels were measured using flow cytometry. Samples from 10 selected patients were sequenced, and verification was performed with advanced TaqMan assays in samples from all patients. Urinary particle concentrations significantly increased in patients with AKI after surgery, with the percentage of EV positive for CD105 and ß1-integrin also increasing. Pre-surgery podocalyxin-positive EV were significantly lower in patients with AKI. Their levels correlated with the severity of the injury. Pre-operative miR-125a-5p was expressed at lower levels in urine from patients with AKI when adjusted for urinary creatinine. Levels of miR-10a-5p were lower after surgery in AKI patients and its levels correlated with the severity of the injury. Pre-operative levels of podocalyxin EVs, urinary particle concentrations and miR-125a-5p had moderate AKI predictive value and, in a logistic model together with ICU lactate levels, offered good (AUC = 82%) AKI prediction.

Asunto(s)

Lesión Renal Aguda , Procedimientos Quirúrgicos Cardíacos , Vesículas Extracelulares , MicroARNs , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/orina , Biomarcadores/orina , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Creatinina/orina , Humanos , MicroARNs/orina