EValuating the Effect of periopeRaTIve empaGliflOzin on cardiac surgery associated acute kidney injury: rationale and design of the VERTIGO study.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a serious complication in patients undergoing cardiac surgery with extracorporeal circulation (ECC) that increases postoperative complications and mortality. CSA-AKI develops due to a combination of patient- and surgery-related risk factors that enhance renal ischemia-reperfusion injury. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) such as empagliflozin reduce renal glucose reabsorption, improving tubulo-glomerular feedback, reducing inflammation and decreasing intraglomerular pressure. Preclinical studies have observed that SGLT2i may provide significant protection against renal ischemia-reperfusion injury due to their effects on inadequate mitochondrial function, reactive oxygen species activity or renal peritubular capillary congestion, all hallmarks of CSA-AKI. The VERTIGO (EValuating the Effect of periopeRaTIve empaGliflOzin) trial is a Phase 3, investigator-initiated, randomized, double-blind, placebo-controlled, multicenter study that aims to explore whether empagliflozin can reduce the incidence of adverse renal outcomes in cardiac surgery patients. Methods: The VERTIGO study (EudraCT: 2021-004938-11) will enroll 608 patients that require elective cardiac surgery with ECC. Patients will be randomly assigned in a 1:1 ratio to receive either empagliflozin 10 mg orally daily or placebo. Study treatment will start 5 days before surgery and will continue during the first 7 days postoperatively. All participants will receive standard care according to local practice guidelines. The primary endpoint of the study will be the proportion of patients that develop major adverse kidney events during the first 90 days after surgery, defined as ≥25% renal function decline, renal replacement therapy initiation or death. Secondary, tertiary and safety endpoints will include rates of AKI during index hospitalization, postoperative complications and observed adverse events. Conclusions: The VERTIGO trial will describe the efficacy and safety of empagliflozin in preventing CSA-AKI. Patient recruitment is expected to start in May 2024.

Impact of intra-abdominal pressure on early kidney transplant outcomes.

Increased intra-abdominal pressure (IAP) is common among post-surgical patients and may cause organ dysfunction. However, its impact after kidney transplantation on early postoperative complications and graft recovery remains unclear. We designed a prospective, observational cohort study to describe the prevalence and determinants of IAP, as well as its effect on delayed graft function, postoperative complications, and graft recovery. IAP was measured in 205 kidney transplant recipients every 8 h during the first 72 h after surgery using the urinary bladder technique. Intra-abdominal hypertension was defined as IAP ≥ 12 mmHg. Patients were followed for 6 months or until graft failure/death. Mean IAP was 12 ± 3.3 mmHg within the first 24 h. 78% of subjects presented with intra-abdominal hypertension during the first 72 h. Increased IAP was associated with higher renal resistive index [r = 0.213; P = 0.003] and lower urine output [r = - 0.237; P < 0.001]. 72 h mean IAP was an independent risk factor for delayed graft function [OR: 1.31; 95% CI: 1.13-1.51], postoperative complications [OR: 1.17; 95% CI: 1.03-1.33], and absence of graft function recovery [HR for graft function recovery: 0.94; 95% CI: 0.88-0.99]. Increased IAP was highly prevalent after transplantation and was independently associated with delayed graft function, postoperative complications, and absence of graft function recovery. Routine IAP monitoring should be considered post-transplantation to facilitate early recognition of relevant complications.

Impact of Tricuspid Regurgitation Severity and Repair on Aortic Valve Replacement.

BACKGROUND: Aortic stenosis is one of the most prevalent valve diseases but is rarely accompanied by tricuspid regurgitation. Our objective was to analyze the impact of tricuspid regurgitation severity and its surgical treatment on prognosis of patients undergoing aortic valve replacement. METHODS: This was a retrospective cohort study including all patients presenting with aortic stenosis with some degree of tricuspid regurgitation between 2001 and 2018. Patients were grouped according to the degree of tricuspid regurgitation. RESULTS: From a sample of 8080 patients with aortic stenosis, 143 (1.8%) presented with more than trace tricuspid regurgitation. Among patients with mild, moderate, or severe tricuspid regurgitation, we observed no differences in 30-day (15.1% vs 14.8% vs 8.7%; P = .727), 12-month (51.2% vs 56% vs 55%; P = .892), or 5-year (64% vs 73.3% vs 66.7%; P = .798) survival. Aortic valve replacement plus tricuspid annuloplasty, when compared with aortic valve replacement only was associated with longer intensive care unit stay (9 vs 3 days; P = .043) but not higher 30-day (0% vs 15.5%; P = .112), 12-month (38.5% vs 54.3%; P = .278), or 5-year mortality (57.1% vs 67.1%; P = .594). Only history of liver disease and postoperative major morbidity were independent predictors of survival 30 days, 12 months and 5 years after surgery. CONCLUSIONS: Severity of tricuspid regurgitation in patients with aortic stenosis was not associated with increased mortality. Tricuspid annuloplasty did not improve survival in this subset of patients but was associated with increased postoperative morbidity.

A randomized prospective multicenter trial for stroke prevention by prophylactic surgical closure of the left atrial appendage in patients undergoing bioprosthetic aortic valve surgery--LAA-CLOSURE trial protocol.

Patients undergoing surgical aortic valve replacement (SAVR) are at high risk for atrial fibrillation (AF) and stroke after surgery. There is an unmet clinical need to improve stroke prevention in this patient population. The LAA-CLOSURE trial aims to assess the efficacy and safety of prophylactic surgical closure of the left atrial appendage for stroke and cardiovascular death prevention in patients undergoing bioprosthetic SAVR. This randomized, open-label, prospective multicenter trial will enroll 1,040 patients at 13 European sites. The primary endpoint is a composite of cardiovascular mortality, stroke and systemic embolism at 5 years. Secondary endpoints include cardiovascular mortality, stroke, systemic embolism, bleed fulfilling academic research consortium (BARC) criteria, hospitalization for decompensated heart failure and health economic evaluation. Sample size is based on 30% risk reduction in time to event analysis of primary endpoint. Prespecified reports include 30-day safety analysis focusing on AF occurrence and short-term outcomes and interim analyses at 1 and 3 years for primary and secondary outcomes. Additionally, substudies will be performed on the completeness of the closure using transesophageal echocardiography/cardiac computed tomography and long-term ECG recording at one year after the operation.

Near-Infrared Spectroscopy Monitoring in Cardiac and Noncardiac Surgery: Pairwise and Network Meta-Analyses.

Goal-directed therapy based on brain-oxygen saturation (bSo2) is controversial and hotly debated. While meta-analyses of aggregated data have shown no clinical benefit for brain near-infrared spectroscopy (NIRS)-based interventions after cardiac surgery, no network meta-analyses involving both major cardiac and noncardiac procedures have yet been undertaken. Randomized controlled trials involving NIRS monitoring in both major cardiac and noncardiac surgery were included. Aggregate-level data summary estimates of critical outcomes (postoperative cognitive decline (POCD)/postoperative delirium (POD), acute kidney injury, cardiovascular events, bleeding/need for transfusion, and postoperative mortality) were obtained. NIRS was only associated with protection against POCD/POD in cardiac surgery patients (pooled odds ratio (OR)/95% confidence interval (CI)/I2/number of studies (n): 0.34/0.14-0.85/75%/7), although a favorable effect was observed in the analysis, including both cardiac and noncardiac procedures. However, the benefit of the use of NIRS monitoring was undetectable in Bayesian network meta-analysis, although maintaining bSo2 > 80% of the baseline appeared to have the most pronounced impact. Evidence was imprecise regarding acute kidney injury, cardiovascular events, bleeding/need for transfusion, and postoperative mortality. There is evidence that brain NIRS-based algorithms are effective in preventing POCD/POD in cardiac surgery, but not in major noncardiac surgery. However, the specific target bSo2 threshold has yet to be determined.

A New Surgical Site Infection Risk Score: Infection Risk Index in Cardiac Surgery.

Various scoring systems attempt to predict the risk of surgical site infection (SSI) after cardiac surgery, but their discrimination is limited. Our aim was to analyze all SSI risk factors in both coronary artery bypass graft (CABG) and valve replacement patients in order to create a new SSI risk score for such individuals. A priori prospective collected data on patients that underwent cardiac surgery (n = 2020) were analyzed following recommendations from the Reporting of studies Conducted using Observational Routinely collected health Data (RECORD) group. Study participants were divided into two periods: the training sample for defining the new tool (2010­2014, n = 1298), and the test sample for its validation (2015­2017, n = 722). In logistic regression, two preoperative variables were significantly associated with SSI (odds ratio (OR) and 95% confidence interval (CI)): diabetes, 3.3/2­5.7; and obesity, 4.5/2.2­9.3. The new score was constructed using a summation system for punctuation using integer numbers, that is, by assigning one point to the presence of either diabetes or obesity. The tool performed better in terms of assessing SSI risk in the test sample (area under the Receiver-Operating Characteristic curve (aROC) and 95% CI, 0.67/055­0.76) compared to the National Nosocomial Infections Surveillance (NNIS) risk index (0.61/0.50­0.71) and the Australian Clinical Risk Index (ACRI) (0.61/0.50­0.72). A new two-variable score to preoperative SSI risk stratification of cardiac surgery patients, named Infection Risk Index in Cardiac surgery (IRIC), which outperforms other classical scores, is now available to surgeons. Personalization of treatment for cardiac surgery patients is needed.

Impact of an ultraviolet air sterilizer on cardiac surgery patients, a randomized clinical trial.

BACKGROUND: Numerous studies have evaluated the use of ultraviolet-C devices for terminal disinfection in hospitals, however, to date there is little information about the device's final impact on patients. We investigated the effect of an ultraviolet air sterilizer (UVAS) on the clinical outcomes of cardiac surgery patients. MATERIALS AND METHODS: This random, prospective and non-interventional study included 1097 adult patients undergoing elective cardiac surgery: 522 stayed in an ICU room with UVAS (Medixair®) and 575 patients ICU room without UVAS and were used as a control. The primary outcome measure was to evaluate the effect of a UVAS on the overall prevalence of nosocomial infections in postoperative cardiac patients in ICUs. RESULTS: No significant differences in ventilator-associated pneumonia (4.6% vs. 5.0%, p=0.77) and total infection (14.0% vs. 15.5%, p=0.45) rates were detected in patients with and without the UVAS. The length of stay in the intensive care unit and at the hospital was similar in both groups, UVAS (4.6 (8.2) days and 18.3 (5.5) days) and without UVAS (4.6 (7.3) days and 19.2 (18.6) days). The 30-day in-hospital mortality rate was 5.3%, no significant differences between groups were observed (p=0.053). CONCLUSION: Novel ultraviolet-C technology has not been shown to significantly reduce nosocomial infections or mortality rates in cardiac surgery patients.

Surgery for acute infective endocarditis: epidemiological data from a Spanish nationwide hospital-based registry.

OBJECTIVES: Infective endocarditis (IE) is a serious and eventually lethal disease with rising incidence in the past couple of decades. The aim of this study was to evaluate the contemporary epidemiological trends of surgical endocarditis patients, to analyse the clinical outcomes and to study their profile, associated prognostic factors and costs. METHODS: This is a retrospective study of all patients admitted for IE in Spanish hospitals and discharged between 1 January 1997 and 31 December 2014. Data were extracted from the minimum basic data set of the National Surveillance System for Hospital Data in Spain provided by the Spanish Ministry of Health. Hospitalizations, comorbidities, outcomes and costs were analysed. RESULTS: In total, 34 399 patients with IE were included; 15.7% of patients received surgical treatment and 84.3% received medical treatment only. Surgical patients were mostly men (71.9%) and had a lower mean age (59.2 ± 16.08 years) than the medical treatment group (P < 0.0001). Mortality among surgical patients showed a decreasing trend between 1997 (32.0%) and 2014 (22.7%) and increased with age (47.6% in ≥85 years of age). Length of hospital stay and the percentage of patients with organ dysfunction were also higher in this group. The cost of the surgical treatment group was higher and increased since 1997 (15 259.22 euros), remaining stable from 2010 (40 700 euros) (P < 0.0001). CONCLUSIONS: Surgical treatment in IE has trended upwards in Spain during the last 2 decades. Patients are getting older and more frequently experience organ dysfunction. Mortality ratio steadily declined without changes in the length of hospital stay.

Perceval Less Invasive Aortic Replacement Register: multicentric Spanish experience with the Perceval S bioprosthesis in moderate-high-risk aortic surgery.

OBJECTIVES: The development of new percutaneous and surgical techniques has reduced the risk associated with aortic valve replacement procedures. We present the results of a Spanish register after initiating a programme for sutureless prostheses in moderate-high-risk patients. METHODS: This prospective multicentre study was carried out from November 2013 to November 2016. Data were obtained from 448 patients in whom a Perceval S prosthesis was implanted. RESULTS: The mean age was 79.24 (standard deviation [SD] 4.1) years, and 61.2% were women. The estimated EuroSCORE I log risk was 11.15% (SD 7.6), with an observed mortality of 4.4% (20 patients). Isolated aortic valve replacement was performed on 69.26% of patients, with 64% involving ministernotomy. The incidence of neurological events was 2%, with 2 permanent cerebrovascular accidents, and 41 (9.2%) patients were implanted with a permanent endocavitary pacemaker. At discharge, 12 (2.6%) patients presented minimal periprosthetic leakage, and 4 (0.89%) patients had moderate leakage. There were 3 reinterventions during follow-up (2 endocarditis and 1 dysfunction due to periprosthetic leak progression). The mean gradient at discharge, 6 months and 1 year was 12.94 (SD 5.3) mmHg, 12.19 (SD 4.7) mmHg and 11.77 (SD 4.7) mmHg, respectively; 59.4% of the patients were octogenarians, with a survival rate of 98% at both 6 months and 1 year at discharge. There was neither valve migration nor early structural degeneration. The mean follow-up was 12 ± 3 months. The 6-month and 1-year mortality was 1.4% and 2.1%, respectively. CONCLUSIONS: This is a prospective multicentric study on the largest cohort of patients with sutureless valves conducted in Spain to date. It is a reproducible procedure that has enabled surgery on patients with a moderate-high risk with low morbidity and mortality, providing good haemodynamic results.

Rationale and design of a multicentre, prospective, randomised, controlled clinical trial to evaluate the efficacy of the adipose graft transposition procedure in patients with a myocardial scar: the AGTP II trial.

INTRODUCTION: Cardiac adipose tissue is a source of progenitor cells with regenerative capacity. Studies in rodents demonstrated that the intramyocardial delivery of cells derived from this tissue improves cardiac function after myocardial infarction (MI). We developed a new reparative approach for damaged myocardium that integrates the regenerative properties of cardiac adipose tissue with tissue engineering. In the adipose graft transposition procedure (AGTP), we dissect a vascularised flap of autologous pericardial adipose tissue and position it over the myocardial scarred area. Following encouraging results in acute and chronic MI porcine models, we performed the clinical trial (NCT01473433, AdiFLAP trial) to evaluate safety in patients with chronic MI undergoing coronary artery bypass graft. The good safety profile and trends in efficacy warranted a larger trial. STUDY DESIGN: The AGTP II trial (NCT02798276) is an investigator initiated, prospective, randomised, controlled, multicentre study to assess the efficacy of the AGTP in 108 patients with non-revascularisable MI. Patients will be assigned to standard clinical practice or the AGTP. The primary endpoint is change in necrotic mass ratio by gadolinium enhancement at 91 and 365 days. Secondary endpoints include improvement in regional contractibility by MRI at 91 and 365 days; changes in functional MRI parameters (left ventricular ejection fraction, left and right ventricular geometric remodelling) at 91 and 365 days; levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at 7, 91 and 365 days; appearance of arrhythmias from 24 hour Holter monitoring at 24 hours, and at 91 and 365 days; all cause death or re-hospitalisation at 365 days; and cardiovascular death or re-hospitalisation at 365 days. ETHICS AND DISSEMINATION: The institutional review board approved the trial which will comply with the Declaration of Helsinki. All patients will provide informed consent. It may offer a novel, effective and technically simple technique for patients with no other therapeutic options. The results will be submitted to indexed medical journals and national and international meetings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02798276, pre-results.

Procalcitonin and white blood cells, combined predictors of infection in cardiac surgery patients.

BACKGROUND: Sepsis is strongly associated with an increased risk of postoperative mortality, longer length of hospital stay, and elevated health care costs. Early clinical symptoms overlap with those of systemic inflammatory response syndrome, a response that commonly occurs after cardiac surgery with cardiopulmonary bypass. Since a combination of biomarkers has been demonstrated to improve the prediction of postoperative infection, the objective of the present study was to test whether the combination of C-reactive protein (CRP), white blood cells (WBC), and procalcitonin (PCT) is able to predict postoperative infection in a large cohort of cardiac surgery patients. MATERIAL AND METHODS: Case-control study involving 423 patients who underwent cardiac surgery with cardiopulmonary bypass. Patients were retrospectively classified into two groups based on whether they developed severe sepsis or septic shock during the postoperative period. Blood samples for biological measurements (PCT, CRP, and WBC) were drawn on the first day in the intensive care unit, then once daily in the morning until the 10th postoperative day. RESULTS: CRP median values were similar in both groups. WBC and PCT median values were significantly higher in patients with infection than without during the first 10 postoperative days. With elevation cutoffs ≤3 times (OR: 4.058; 95% CI: 2.206-7.463; P = 0.001) and ≥4 times (OR: 10.274, 95% CI: 3.690-28.604; P < 0.001), the median value for PCT (1.7 ng/mL) and/or WBC (13,000 cells/mm3) on the second postoperative day was significantly associated with the development of infection. CONCLUSIONS: The goal of this study was to use a large cohort of cardiac surgery patients to ensure that the results were representative of this population. The combination of PCT and WBC levels over the first three postoperative days was able to predict postoperative infection within the 30 d following cardiac surgery.

Risk score for cardiac surgery in active left-sided infective endocarditis.

OBJECTIVE: To develop and validate a calculator to predict the risk of in-hospital mortality in patients with active infective endocarditis (IE) undergoing cardiac surgery. METHODS: Thousand two hundred and ninety-nine consecutive patients with IE were prospectively recruited (1996-2014) and retrospectively analysed. Left-sided patients who underwent cardiac surgery (n=671) form our study population and were randomised into development (n=424) and validation (n=247) samples. Variables statistically significant to predict in-mortality were integrated in a multivariable prediction model, the Risk-Endocarditis Score (RISK-E). The predictive performance of the score and four existing surgical scores (European System for Cardiac Operative Risk Evaluation (EuroSCORE) I and II), Prosthesis, Age ≥70, Large Intracardiac Destruction, Staphylococcus, Urgent Surgery, Sex (Female) (PALSUSE), EuroSCORE ≥10) and Society of Thoracic Surgeons's Infective endocarditis score (STS-IE)) were assessed and compared in our cohort. Finally, an external validation of the RISK-E in a separate population was done. RESULTS: Variables included in the final model were age, prosthetic infection, periannular complications, Staphylococcus aureus or fungi infection, acute renal failure, septic shock, cardiogenic shock and thrombocytopaenia. Area under the receiver operating characteristic curve in the validation sample was 0.82 (95% CI 0.75 to 0.88). The accuracy of the other surgical scores when compared with the RISK-E was inferior (p=0.010). Our score also obtained a good predictive performance, area under the curve 0.76 (95% CI 0.64 to 0.88), in the external validation. CONCLUSIONS: IE-specific factors (microorganisms, periannular complications and sepsis) beside classical variables in heart surgery (age, haemodynamic condition and renal failure) independently predicted perioperative mortality in IE. The RISK-E had better ability to predict surgical mortality in patients with IE when compared with other surgical scores.