Benefit of isolated surgical valve repair or replacement for functional tricuspid regurgitation and long-term outcomes stratified by the TRI-SCORE.

BACKGROUND AND AIMS: Severe tricuspid regurgitation (TR) is associated with increased mortality rates, but benefit of its correction and ideal timing are not clearly determined. This study aimed to identify patient subsets who might benefit from surgery. METHODS: In TRIGISTRY, an international cohort study of consecutive patients with severe isolated functional TR (33 centers, 10 countries), survival rates up to 10 years were compared between patients who underwent isolated tricuspid valve (TV) surgery (repair or replacement) and those conservatively managed, overall and according to TRI-SCORE category (low: ≤3, intermediate: 4-5, high: ≥6). RESULTS: 1,217 were managed conservatively, and 551 underwent isolated TV surgery (200 repairs, 351 replacements). TRI-SCORE distribution was 33% low, 32% intermediate, and 35% high. At 10 years, survival rates were similar between surgical and conservative management (41% vs. 36%; hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.88-1.08, P=0.57). Surgery improved survival compared to conservative management in the low TRI-SCORE category (72% vs. 44%; HR 0.27; 95% CI 0.20-0.37, P<0.0001), but not in the intermediate (36% vs. 37%, HR 1.17; 95%CI 0.98-1.40, P=0.09) or high categories (20% vs. 24%; HR 1.06; 95% CI 0.91-1.25, P=0.45). Both repair and replacement improved survival in the low TRI-SCORE category (84% and 61% vs. 44%; HR 0.11; 95% CI 0.06-0.19, P<0.0001, and HR 0.65; 95% CI 0.47-0.90, P=0.009). Repair showed benefit in the intermediate category (59% vs. 37%; HR 0.49; 95% CI 0.35-0.68, P<0.0001) while replacement was possibly harmful (25% vs. 37%; HR 1.43; 95% CI 1.18-1.72, P=0.0002). CONCLUSIONS: Higher survival rates were observed with repair than replacement and benefit of intervention declined as TRI-SCORE increased with no benefit of any type of surgery in the high TRI-SCORE category. These results emphasize the importance of timely intervention and patient selection to achieve the best outcomes and the need for randomized controlled trials. TRIAL REGISTRATION: TRIGISTRY: ClinicalTrials.gov, NCT05825898.

Hemolysis Index, Carboxyhemoglobin, and Methemoglobin for the Early Identification of Patients at Risk for Cardiac Surgery-Associated Acute Kidney Injury.

OBJECTIVES: Hemolysis is a contributor to CS-AKI. Biochemistry analyzers provide a hemolysis index to quantify in vitro hemolysis, a condition that can, for example, affect the accuracy of potassium concentration measurements. We aimed to assess whether the postoperative plasma level of the hemolysis index (HIpostoperative) could aid the early recognition of patients at risk for cardiac surgery-associated acute kidney injury (CS-AKI) and also to evaluate other hemolysis indicators: plasma carboxyhemoglobin (COHbpostoperative) and methemoglobin (MetHbpostoperative). DESIGN: One-year retrospective study. SETTING: University hospital. PARTICIPANTS: Patients undergoing elective cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In 1090 patients, the median HIpostoperative was higher in patients who developed CS-AKI compared to patients who did not (11 mg/dL [interquartile range (IQR), 5-38 mg/dL] v 7 mg/dL [IQR, 3-16 mg/dL]; p < 0.001). HIpostoperative refined the early recognition of CS-AKI: the area under the precision-recall curve (AUPRC) for HIpostoperative was 37% (95% confidence interval [CI], 31%-42%), whereas the AUPRC associated with no discriminative power, equal to the prevalence of CS-AKI in the whole population, was 21%. Among the 611 patients with measurements for all 3 biomarkers, the AUPRC of HIpostoperative was higher than that of COHbpostoperative or MetHbpostoperative (+6.6% and +7.4% respectively; p < 0.0001 for both). Unlike COHbpostoperative or MetHbpostoperative, the incorporation of HIpostoperative into a model (trained on a sample then validated in another sample) of CS-AKI early recognition significantly enhanced its performance, with a +1.9% (95% CI, 1.6%-2.1%) increase in AUPRC (p < 0.0001). CONCLUSIONS: Elevated HIpostoperative represents an early alert signal for the development of CS-AKI. Our findings support the incorporation of HIpostoperative, a readily available biomarker, into predictive scores of CS-AKI.

TRI-SCORE: a new risk score for in-hospital mortality prediction after isolated tricuspid valve surgery.

AIMS: Isolated tricuspid valve surgery (ITVS) is considered to be a high-risk procedure, but in-hospital mortality is markedly variable. This study sought to develop a dedicated risk score model to predict the outcome of patients after ITVS for severe tricuspid regurgitation (TR). METHODS AND RESULTS: All consecutive adult patients who underwent ITVS for severe non-congenital TR at 12 French centres between 2007 and 2017 were included. We identified 466 patients (60 ± 16 years, 49% female, functional TR in 49%). In-hospital mortality rate was 10%. We derived and internally validated a scoring system to predict in-hospital mortality using multivariable logistic regression and bootstrapping with 1000 re-samples. The final risk score ranged from 0 to 12 points and included eight parameters: age ≥70 years, New York Heart Association Class III-IV, right-sided heart failure signs, daily dose of furosemide ≥125 mg, glomerular filtration rate <30 mL/min, elevated bilirubin, left ventricular ejection fraction <60%, and moderate/severe right ventricular dysfunction. Tricuspid regurgitation mechanism was not an independent predictor of outcome. Observed and predicted in-hospital mortality rates increased from 0% to 60% and from 1% to 65%, respectively, as the score increased from 0 up to ≥9 points. Apparent and bias-corrected areas under the receiver operating characteristic curves were 0.81 and 0.75, respectively, much higher than the logistic EuroSCORE (0.67) or EuroSCORE II (0.63). CONCLUSION: We propose TRI-SCORE as a dedicated risk score model based on eight easy to ascertain parameters to inform patients and physicians regarding the risk of ITVS and guide the clinical decision-making process of patients with severe TR, especially as transcatheter therapies are emerging (www.tri-score.com).

Plasma haemolysis index and interleukine-6 for the early prediction of cardiac surgery-associated acute kidney injury. A proof-of-concept study.

INTRODUCTION: Haemolysis and inflammation contribute to cardiac surgery-associated acute kidney injury (CS-AKI). We aimed to assess the performance of plasma haemolysis index (HI) and interleukine-6 (IL-6) for the prediction of all-stage CS-AKI. We also assessed their ability to predict moderate-to-severe CS-AKI and to discriminate persistent from transient CS-AKI. METHODS: Adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) were prospectively included. Haemolysis index and IL-6 were measured immediately after the end of CPB and 6 hours later. Correction for haemodilution relied upon changes in albuminaemia. Persistent CS-AKI was defined as a steady/increasing CS-AKI stage between the 48th and the 60th postoperative hour as compared with the worst stage observed within the 48 first hours. RESULTS: Among 82 patients, CS-AKI occurred in 37 (45%) patients. Postoperative HI and IL-6 were positively correlated to the duration of CPB (r ≤ 0.51, p ≤ 0.0003). Whether we considered isolated measurements of HI or IL-6, their indexation to haemodilution or not, their kinetics and/or their combination, the prediction of all stage CS-AKI was inaccurate (area under the receiver operating characteristic curve [AUCROC]≤ 0.68) whereas moderate-to-severe CS-AKI (6 patients only) was predicted with an honourable performance (AUCROC = 0.77 [95%CI 0.67;0.86] and 0.87 [95%CI 0.77;0.93] for HI and IL-6, respectively). The persistent/transient nature of CS-AKI was inaccurately predicted (AUCROC ≤ 0.68). CONCLUSIONS: In a population in which most CS-AKI cases were mild, although they frequently (41%) persisted >48 hours, CS-AKI was inaccurately predicted by HI and/or IL-6. A better performance for moderate-to-severe CS-AKI prediction is likely. These preliminary findings are yet to be validated.

Replacement Myocardial Fibrosis in Patients With Mitral Valve Prolapse: Relation to Mitral Regurgitation, Ventricular Remodeling, and Arrhythmia.

BACKGROUND: Mitral valve prolapse (MVP) is a frequent disease that can be complicated by mitral regurgitation (MR), heart failure, arterial embolism, rhythm disorders, and death. Left ventricular (LV) replacement myocardial fibrosis, a marker of maladaptive remodeling, has been described in patients with MVP, but the implications of this finding remain scarcely explored. We aimed at assessing the prevalence, pathophysiological and prognostic significance of LV replacement myocardial fibrosis through late gadolinium enhancement (LGE) by cardiac magnetic resonance in patients with MVP. METHODS: Four hundred patients (53±15 years of age, 55% male) with MVP (trace to severe MR by echocardiography) from 2 centers, who underwent a comprehensive echocardiography and LGE cardiac magnetic resonance, were included. Correlates of replacement myocardial fibrosis (LGE+), influence of MR degree, and ventricular arrhythmia were assessed. The primary outcome was a composite of cardiovascular events (cardiac death, heart failure, new-onset atrial fibrillation, arterial embolism, and life-threatening ventricular arrhythmia). RESULTS: Replacement myocardial fibrosis (LGE+) was observed in 110 patients (28%; 91 with myocardial wall including 71 with basal inferolateral wall, 29 with papillary muscle). LGE+ prevalence was 13% in trace-mild MR, 28% in moderate MR, and 37% in severe MR, and was associated with specific features of mitral valve apparatus, more dilated LV and more frequent ventricular arrhythmias (45% versus 26%, P<0.0001). In trace-mild MR, despite the absence of significant volume overload, abnormal LV dilatation was observed in 16% of patients and ventricular arrhythmia in 25%. Correlates of LGE+ in multivariable analysis were LV mass (odds ratio, 1.01 [95% CI, 1.002-1.017], P=0.009) and moderate-severe MR (odds ratio, 2.28 [95% CI, 1.21-4.31], P=0.011). LGE+ was associated with worse 4-year cardiovascular event-free survival (49.6±11.7 in LGE+ versus 73.3±6.5% in LGE-, P<0.0001). In a stepwise multivariable Cox model, MR volume and LGE+ (hazard ratio, 2.6 [1.4-4.9], P=0.002) were associated with poor outcome. CONCLUSIONS: LV replacement myocardial fibrosis is frequent in patients with MVP; is associated with mitral valve apparatus alteration, more dilated LV, MR grade, and ventricular arrhythmia; and is independently associated with cardiovascular events. These findings suggest an MVP-related myocardial disease. Last, cardiac magnetic resonance provides additional information to echocardiography in MVP.

Outcome of Temporary Circulatory Support As a Bridge-to-Left Ventricular Assist Device Strategy in Cardiogenic Shock Patients.

OBJECTIVES: Temporary circulatory support (TCS) as a bridge-to-left ventricular assist device (BTL) in cardiogenic shock patients has been increasing, but limited data exists on this BTL strategy. We aimed at analyzing the outcome of BTL patients in a population of cardiogenic shock patients compared with those without TCS at the time of the left ventricular assist device (LVAD) surgery and identify predictors of postoperative mortality in this specific population. DESIGN: A multicenter retrospective observational study conducted in 19 centers from 2006 to 2016. SETTING: Nineteen French centers. PATIENTS: A total of 329 cardiogenic shock patients at the time of LVAD implantation were analyzed. Patients were divided in three groups: those under TCS at the time of LVAD implantation (n = 173), those with TCS removal before LVAD surgery (n = 24), and those who did not undergo a bridging strategy (n = 152). Primary endpoint was 30-day mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the BTL group, 68 (39.3%), 18 (10.4%), and 15 (8.7%) patients were under venoarterial extracorporeal membrane oxygenation, Impella, and IABP support alone, and 72 patients (20.6%) were under multiple TCS support. BTL patients presented similar 30 days survival compared with the TCS removal and non-BTL groups. However, BTL group had a significantly longer ICU duration stay, with two-fold duration of mechanical ventilation time, but the three groups experienced similar postoperative complications. Multivariate analysis identified three independent predictors of mortality in the BTL group: combined surgery with LVAD, body mass index (BMI), and heart failure (HF) duration. BTL strategy was not an independent predictor of mortality in cardiogenic shock patients who underwent LVAD. CONCLUSIONS: BTL strategy is not associated with a lower survival among cardiogenic shock patients with LVAD implantation. Predictors of mortality are combined surgery with LVAD, higher BMI, and HF duration.

Mitral valve-in-valve and valve-in-ring procedures: Midterm outcomes in a French nationwide registry.

OBJECTIVES: Report contemporary outcomes in patients included in the Mitragister registry and treated with transcatheter mitral valve implantation for failed surgical annuloplasty rings or deteriorated bioprosthesis. BACKGROUND: Midterm survival rates have been reported, but little is known about contemporary morbimortality endpoints. METHODS: The primary safety outcome was the technical success rate. The primary efficacy composite endpoint was a composite of cardiovascular mortality and heart failure hospitalizations. RESULTS: From 2016 to 2021, 102 patients (median age: 81 [74;84] years, 61% female, Euroscore II 11.0% [7.8;16.0]) undergoing valve-in-valve (ViV; n = 89) or valve-in-ring (ViR; n = 13) procedures were consecutively included. At baseline, ViR group patients had worse left ventricular ejection fraction (50% vs. 60%; p = 0.004) and more frequently severe regurgitation (46% vs. 15%; p = 0.014). The primary safety outcome was 95%: 77% and 98% in the ViR and ViV populations, respectively, (p = 0.014). At intermediate follow-up (6-12 months) clinical improvement was notable, 88% of the patients were in NYHA class ≤ II (vs. 25% at baseline; p < 0.001). At a mean follow-up of 17.1 ± 11.0 months, the primary efficacy composite reached 27%. By multivariate analysis, paravalvular leak (PVL) was the only independent predictor (hazard ratio: 2.39, 95% confidence interval: 1.08-5.29; p = 0.031) while ViR was not found statistically associated (p = 0.456). CONCLUSIONS: This study confirms the safety and efficacy of the mitral ViV procedure. ViR patients appear at higher risk of procedural complications. The presence of PVL could be associated with markedly worse midterm prognosis. Whatever the intervention, procedural strategies to reduce PVL incidence remain to be assessed to prevent latter adverse outcomes.

Management and outcomes of ventricular septal defects after acute myocardial infarction: A multicenter retrospective study.

BACKGROUND AND AIM: The mortality rate of patients with post-myocardial infarction (MI) ventricular septal defects (VSDs) is high, and the benefit of surgery is unclear. We aimed to investigate the management and outcomes of post-MI VSD over a 10-year period in a large cohort. METHODS: Data of patients with post-MI VSD admitted in three French university hospitals from 2008 to 2019 were examined. The characteristics of those who underwent surgery were compared with those who received medical treatment. Mortality risk factors, survival curves, and outcomes at 30 days and 1 year after treatment were determined. RESULTS: Of the 92 patients whose data were examined, 50 underwent surgery and 42 received exclusive medical treatment. All patients were critically ill. Overall, 76.1% of patients received inotropic support, and 63% received mechanical ventilation. Circulatory assistance, mainly via intra-aortic balloon pump and extra-corporeal membrane oxygenation, was provided to 46.7% patients, with 14.1% requiring a second assistance. The median time to surgery was 4 days. At 1 year, mortality was 46% in those who underwent surgery and 83.3% in those treated medically (p < .001). Survival curves at 1 and 3 months showed major differences, and the survival rate showed little change 30 days after treatment. Cardiogenic shock and cardiac arrest emerged as risk factors for mortality. CONCLUSIONS: In our retrospective, multicenter study, the mortality resulting from post-MI VSD did not seem to improve over the last decade. Although surgery carried considerable risks, it improved survival.

Heparin Anti-Xa Activity, a Readily Available Unique Test to Quantify Apixaban, Rivaroxaban, Fondaparinux, and Danaparoid Levels.

BACKGROUND: Despite their usefulness in perioperative and acute care settings, factor-Xa inhibitor-specific assays are scarcely available, contrary to heparin anti-Xa assay. We assessed whether the heparin anti-Xa assay can (1) be used as a screening test to rule out apixaban, rivaroxaban, fondaparinux, and danaparoid levels that contraindicate invasive procedures according to current guidelines (>30 ng·mL-1, >30 ng·mL-1, >0.1 µg·mL-1, and >0.1 IU·mL-1, respectively), (2) quantify the anticoagulant level if found significant, that is, if it exceeded the abovementioned threshold. METHODS: In the derivation cohort then in the validation cohort, via receiver operating characteristics (ROC) curve analysis, we evaluated the ability of heparin anti-Xa assay to detect levels of factor-Xa inhibitors above or below the abovementioned safety thresholds recommended for an invasive procedure (screening test). Among samples with relevant levels of factor-Xa inhibitor, we determined the conversion factor linking the measured level and heparin anti-Xa activity in a derivation cohort. In a validation cohort, the estimated level of each factor-Xa inhibitor was thus inferred from heparin anti-Xa activity. The agreement between measured and estimated levels of factor-Xa inhibitors was assessed. RESULTS: Among 989 (355 patients) and 756 blood samples (420 patients) in the derivation and validation cohort, there was a strong linear relationship between heparin anti-Xa activities and factor-Xa inhibitors measured level (r = 0.99 [95% confidence interval {CI}, 0.99-0.99]). In the derivation cohort, heparin anti-Xa activity ≤0.2, ≤0.3, <0.1, <0.1 IU·mL-1 reliably ruled out a relevant level of apixaban, rivaroxaban, fondaparinux, and danaparoid, respectively (area under the ROC curve ≥0.99). In the validation cohort, these cutoffs yielded excellent classification accuracy (≥96%). If this screening test indicated relevant level of factor-Xa inhibitor, estimated and measured levels closely agreed (Lin's correlation coefficient close to its maximal value: 95% CI, 0.99-0.99). More than 96% of the estimated levels fell into the predefined range of acceptability (ie, 80%-120% of the measured level). CONCLUSIONS: A unique simple test already widely used to assay heparin was also useful for quantifying these 4 other anticoagulants. Both clinical and economic impacts of these findings should be assessed in a specific study.

Early recognition of cardiac surgery-associated acute kidney injury: lack of added value of TIMP2 IGFBP7 over short-term changes in creatinine (an observational pilot study).

BACKGROUND: For the detection of cardiac surgery-associated acute kidney injury (CS-AKI), the performance of urine tissue inhibitor of metalloproteinase 2 insulin-like growth factor-binding protein 7 (TIMP2 IGFBP7) has never been compared with that of very early changes in plasma creatinine (∆pCr). We hypothesized that, in the context of perioperative haemodilution, lack of postoperative decrease in pCr would be of honourable performance for the detection of CS-AKI. We therefore aimed at comparing these biomarkers and their kinetics (primary objective). As secondary objectives, we assessed plasma neutrophil gelatinase-associated lipocalin (pNGAL), cystatin C (pCysC) and urea (pUrea). We also determined the ability of these biomarkers to early discriminate persistent from transient CS-AKI. METHODS: Patients over 75 years-old undergoing aortic valve replacement with cardiopulmonary bypass (CPB) were included in this prospective observational study. Biomarkers were measured before/after CPB and at the sixth postoperative hour (H6). RESULTS: In 65 patients, CS-AKI occurred in 27 (42%). ∆pCr from post-CPB to H6 (∆pCrpostCPB-H6): outperformed TIMP2 IGFBP7 at H6 and its intra- or postoperative changes: area under the receiver operating characteristic curve (AUCROC) of 0.84 [95%CI:0.73-0.92] vs. ≤0.67 [95%CI:0.54-0.78], p ≤ 0.03. The AUCROC of pNGAL, pCysC and pUrea did not exceed 0.72 [95%CI:0.59-0.83]. Indexing biomarkers levels for blood or urine dilution did not improve their performance. Combining TIMP2 IGFBP7 and ∆pCrpostCPB-H6 was of no evident added value over considering ∆pCrpostCPB-H6 alone. For the early recognition of persistent CS-AKI, no biomarker outperformed ∆pCrpostCPB-H6 (AUCROC = 0.69 [95%CI:0.48-0.85]). CONCLUSIONS: In this hypothesis-generating study mostly testing early detection of mild CS-AKI, there was no evident added value of the tested modern biomarkers over early minimal postoperative changes in pCr: despite the common perioperative hemodilution in the setting of cardiac surgery, if pCr failed to decline within the 6 h after CPB, the development of CS-AKI was likely. Confirmatory studies with more severe forms of CS-AKI are required.

A simplified delivery frozen elephant trunk technique to reduce circulatory arrest time in hybrid aortic arch surgery.

A simplified delivery technique for the frozen elephant trunk procedure allows the distal suture to be performed on a perfused and loaded aorta in moderate hypothermia-or even normothermia-reducing circulatory arrest time to just a few minutes. Two surgical sealing tourniquets are placed around the aortic arch, usually between the brachiocephalic trunk (BCT) and the left common carotid artery and the aorta is cross-clamped and cardioplegia started. Once in mild hypothermia, the BCT is disconnected and circulatory arrest is initiated while cerebral perfusion is maintained. This modified technique can be used in all pathologies, including dissections.

Isolated tricuspid valve surgery: impact of aetiology and clinical presentation on outcomes.

AIMS: The aim of this study was to identify determinants of in-hospital and mid-term outcomes after isolated tricuspid valve surgery (ITVS) and more specifically the impact of tricuspid regurgitation (TR) mechanism and clinical presentation. METHODS AND RESULTS: Among 5661 consecutive adult patients who underwent a tricuspid valve (TV) surgery at 12 French tertiary centres in 2007-2017 collected from a mandatory administrative database, we identified 466 patients (8% of all tricuspid surgeries) who underwent an ITVS. Most patients presented with advanced disease [47% in New York Heart Association (NYHA) III/IV, 57% with right-sided heart failure (HF) signs]. Tricuspid regurgitation was functional in 49% (22% with prior left-sided heart valve surgery and 27% isolated) and organic in 51% (infective endocarditis in 31% and other causes in 20%). In-hospital mortality and major complications rates were 10% and 31%, respectively. Rates of survival and survival free of HF readmission were 75% and 62% at 5 years. Patients with functional TR incurred a worse in-hospital mortality than those with organic TR (14% vs. 6%, P = 0.004), but presentation was more severe. Independent determinants of outcomes were NYHA Class III/IV [odd ratios (OR) = 2.7 (1.2-6.1), P = 0.01], moderate/severe right ventricular dysfunction [OR = 2.6 (1.2-5.8), P = 0.02], lower prothrombin time [OR = 0.98 (0.96-0.99), P = 0.008], and with borderline statistical significance, right-sided HF signs [OR = 2.4 (0.9-6.5), P = 0.06] while TR mechanism was not [OR = 0.7 (0.3-1.8), P = 0.88]. CONCLUSION: Isolated TV surgery was associated with high mortality and morbidity, both in hospital and during follow-up, predicted by the severity of the presentation but not by TR mechanism. Our results suggest that TV intervention should be performed earlier in the course of the disease.

Celsior® crystalloid cardioplegia versus standard hyperkalemic normothermic blood cardioplegia: Analysis of myocardial protection in elective mitral valve repair.

INTRODUCTION: With the increase and refinement of video assisted mitral valve surgery, cristalloïd cardioplegia started regaining popularity. The aim of our study was to evaluate the effectiveness of Celsior®, a crystalloid cardioplegic solution, on myocardial protection in elective surgical mitral valve repair in comparison to blood based hyperkalemic cardioplegia. METHODS: In this observational retrospective study, all consecutive elective isolated surgical mitral valve repair where Celsior® or normothermic hyperkalemic blood cardioplegia were used were included. Primary endpoint was any sign of myocardial protection failure (troponin levels, need for inotropic or mechanical support, rhythm disturbances, mortality). Secondary endpoint was Celsior® safety (allergic reactions, bleeding, organ toxicities). RESULTS: From January 2009 to August 2016, 382 patients underwent elective isolated mitral valve repair in whom normothermic hyperkalemic blood cardioplegia (n = 181) or Celsior® (n = 201) were used. There were no statistically significant differences in baseline characteristics including Euroscore 2. Peak troponin (pg/ml) release and 30-days mortality were not statistically different. Need for cardioversion was significantly more frequent in the Celsior® group (47% vs 13%, p < 0.001). There was no statistical difference in post-operative atrial fibrillation, permanent pacemaker implantation, reoperation for bleeding, transfusion, acute kidney injury, haemoglobin at discharge or length of stay. No allergic reaction to Celsior® occurred. CONCLUSION: Effective myocardial protection was achieved with the Celsior® cardioplegic solution with no unexpected toxicity. Celsior® may be an efficacious and safe cardioprotective strategy in mitral valve repair.

High-Flow Therapy by Nasal Cannulae Versus High-Flow Face Mask in Severe Hypoxemia After Cardiac Surgery: A Single-Center Randomized Controlled Study-The HEART FLOW Study.

OBJECTIVE: To determine whether high-flow oxygen therapy by nasal cannulae (HFNC) is more effective than a high-flow face mask (HFFM) in severe hypoxemia. DESIGN: Randomized, single-center, open-labeled, controlled trial. SETTING: University Hospital of Nantes, France. PARTICIPANTS: Cardiac surgery patients presenting oxygen saturation <96% with Venturi mask 50%. INTERVENTION: Oxygenation by HFNC (45 L/min, FIO2 100%) or Hudson RCI non-rebreather face mask with a reservoir bag (15 L/min). MEASUREMENTS AND MAIN RESULTS: The co-primary outcomes were the PaO2/FIO2 ratio at 1 and 24 hours. In the intent-to-treat analysis (90 patients), the mean (standard deviation) PaO2/FIO2 ratios were: after 1 hour, 113.4 (50.2) in HFFM versus 137.8 (57.0) in HFNC (mean difference 24.4, CI 97.5% [2.9-45.9], p = 0.03), and after 24 hours, 106.9 (62.6) in HFFM versus 129.9 (54.0) in HFNC (mean difference 23.0, CI 97.5% [1.5-44.6], p = 0.04). After adjustment on baseline PaO2/FIO2, this difference persisted at 24 hours (p = 0.04). For secondary outcomes, the PaO2/FIO2 ratio after 6 hours was 108.7 (47.9) in HFFM versus 136.0 (45.2) in HFNC (p = 0.01), without difference after 48 hours (p = 0.95). Refractory hypoxemia requiring noninvasive ventilation occurred in 13 (28%) patients in HFNC versus 24 (56%) patients in HFFM (p = 0.007). The HFNC improved satisfaction (p = 0.0002) and reduced mucus dryness (p = 0.003) compared with HFFM. CONCLUSION: In patients with severe hypoxemia after cardiac surgery, PaO2/FIO2 at 1 and 24 hours were higher and the use of noninvasive ventilation was reduced in HFNC compared with HFFM.

Romiplostim as a transfusion saving strategy in 20 patients after heart or lung transplantation: a single centre before-after pilot study.

BACKGROUND: Thrombocytopenia is a common disorder after heart or lung transplantation. Platelet transfusion is often required to maintain haemostasis but represents a specific cause of morbidity and mortality in this setting including alloimmunisation and graft rejection. STUDY DESIGN AND METHODS: As part of a health-care quality improvement project, in a single-centre before-after pilot study, the relevance of a platelet transfusion saving strategy based on romiplostim administration after transplantation was assessed in patients with platelet count <100 × 109/L. Transfusions on days 28 and 90 were compared using propensity matched score for adjustment of demographic characteristics at baseline. The primary outcome was platelet transfusion until day 28 after transplantation. RESULTS: Ninety-three patients were analysed (73 before vs. 20 after). The median [interquartile range] number of platelet concentrate was 1 [0;4.0] before versus 0.5 [0;2.0] in the after period, mean difference 0.5 confidence interval 95% [-0.7 to 1.7], p = 0.39. On day 28, median [interquartile range] red blood cell transfusion was significantly higher in the before versus the after period, 7 [2.0;13.5] versus 6 [1.5;8.5], mean difference 3.2 CI 95% [0.4-6.0], p = 0.02. At 6 months, the rate of patients with de novo anti-human leukocyte antigen alloimmunisation was 45% before versus 53% in the after period (p = 0.56). Deep venous thrombosis was detected in nine patients (12%) before versus seven patients (35%) in the after period (p = 0.04). CONCLUSION: Romiplostim did not significantly reduce platelet transfusion after heart or lung transplantation. Its relevance and safety in a global transfusion strategy remains to be studied in this setting in a large randomised study.

Risk factors and prognostic impact of left ventricular assist device-associated infections.

BACKGROUND: Left ventricular assist device (LVAD)-associated infections may be life-threatening and impact patients' outcome. We aimed to identify the characteristics, risk factors, and prognosis of LVAD-associated infections. METHODS: Patients included in the ASSIST-ICD study (19 centers) were enrolled. The main outcome was the occurrence of LVAD-associated infection (driveline infection, pocket infection, or pump/cannula infection) during follow-up. RESULTS: Of the 652 patients enrolled, 201 (30.1%) presented a total of 248 LVAD infections diagnosed 6.5 months after implantation, including 171 (26.2%), 51 (7.8%), and 26 (4.0%) percutaneous driveline infection, pocket infection, or pump/cannula infection, respectively. Patients with infections were aged 58.7 years, and most received HeartMate II (82.1%) or HeartWare (13.4%). Most patients (62%) had implantable cardioverter-defibrillators (ICDs) before LVAD, and 104 (16.0%) had ICD implantation, extraction, or replacement after the LVAD surgery. Main pathogens found among the 248 infections were Staphylococcus aureus (n = 113' 45.4%), Enterobacteriaceae (n = 61; 24.6%), Pseudomonas aeruginosa (n = 34; 13.7%), coagulase-negative staphylococci (n = 13; 5.2%), and Candida species (n = 13; 5.2%). In multivariable analysis, HeartMate II (subhazard ratio, 1.56; 95% CI, 1.03 to 2.36; P = .031) and ICD-related procedures post-LVAD (subhazard ratio, 1.43; 95% CI, 1.03-1.98; P = .031) were significantly associated with LVAD infections. Infections had no detrimental impact on survival. CONCLUSIONS: Left ventricular assist device-associated infections affect one-third of LVAD recipients, mostly related to skin pathogens and gram-negative bacilli, with increased risk with HeartMate II as compared with HeartWare, and in patients who required ICD-related procedures post-LVAD. This is a plea to better select patients needing ICD implantation/replacement after LVAD implantation.

Elicited and pre-existing anti-Neu5Gc antibodies differentially affect human endothelial cells transcriptome.

Humans cannot synthesize N-glycolylneuraminic acid (Neu5Gc) but dietary Neu5Gc can be absorbed and deposited on endothelial cells (ECs) and diet-induced anti-Neu5Gc antibodies (Abs) develop early in human life. While the interaction of Neu5Gc and diet-induced anti-Neu5Gc Abs occurs in all normal individuals, endothelium activation by elicited anti-Neu5Gc Abs following a challenge with animal-derived materials, such as following xenotransplantation, had been postulated. Ten primary human EC preparations were cultured with affinity-purified anti-Neu5Gc Abs from human sera obtained before or after exposure to Neu5Gc-glycosylated rabbit IgGs (elicited Abs). RNAs of each EC preparation stimulated in various conditions by purified Abs were exhaustively sequenced. EC transcriptomic patterns induced by elicited anti-Neu5Gc Abs, compared with pre-existing ones, were analyzed. qPCR, cytokines/chemokines release, and apoptosis were tested on some EC preparations. The data showed that anti-Neu5Gc Abs induced 967 differentially expressed (DE) genes. Most DE genes are shared following EC activation by pre-existing or anti-human T-cell globulin (ATG)-elicited anti-Neu5Gc Abs. Compared with pre-existing anti-Neu5Gc Abs, which are normal component of ECs environment, elicited anti-Neu5Gc Abs down-regulated 66 genes, including master genes of EC function. Furthermore, elicited anti-Neu5Gc Abs combined with complement-containing serum down-regulated most transcripts mobilized by serum alone. Both types of anti-Neu5Gc Abs-induced a dose- and complement-dependent release of selected cytokines and chemokines. Altogether, these data show that, compared with pre-existing anti-Neu5Gc Abs, ATG-elicited anti-Neu5Gc Abs specifically modulate genes related to cytokine responses, MAPkinase cascades, chemotaxis, and integrins and do not skew the EC transcriptome toward a pro-inflammatory profile in vitro.

Inverse probability weighting to control confounding in an illness-death model for interval-censored data.

Multistate models with interval-censored data, such as the illness-death model, are still not used to any considerable extent in medical research regardless of the significant literature demonstrating their advantages compared to usual survival models. Possible explanations are their uncommon availability in classical statistical software or, when they are available, by the limitations related to multivariable modelling to take confounding into consideration. In this paper, we propose a strategy based on propensity scores that allows population causal effects to be estimated: the inverse probability weighting in the illness semi-Markov model with interval-censored data. Using simulated data, we validated the performances of the proposed approach. We also illustrated the usefulness of the method by an application aiming to evaluate the relationship between the inadequate size of an aortic bioprosthesis and its degeneration or/and patient death. We have updated the R package multistate to facilitate the future use of this method.

Early structural valve deterioration of Mitroflow aortic bioprosthesis: mode, incidence, and impact on outcome in a large cohort of patients.

BACKGROUND: Structural valve deterioration (SVD) is a major flaw of bioprostheses. Early SVD has been suspected in the last models of Mitroflow bioprosthesis. We sought to assess the incidence, mode, and impact of SVD on outcome in a large series of Mitroflow aortic valve replacement. METHODS AND RESULTS: Six hundred seventeen consecutive patients (aged 76.1±6.3 years) underwent aortic valve replacement with a Mitroflow prosthesis (models 12A/LX) between 2002 and 2007. By echocardiography, 39 patients developed early SVD (1.66% per patient-year), with stenosis as the main mode (n=36). Mean delay to SVD was only 3.8±1.4 years, and 5-year SVD-free survival was 91.6% (95% confidence interval [CI], 88.7-94.7) for the whole cohort and 79.8% (95% CI, 71.2-89.4) and 94.0% (95% CI, 90.3-97.8) for 19- and 21-mm sizes, respectively. Among the 39 patients with SVD, 13 patients (33%) had an accelerated SVD once the mean gradient exceeded 30 mm Hg. Valve-related death was 46.2% in this SVD subgroup. Five-year overall survival was 69.6% (95% CI, 65.7-73.9). In multivariable analysis, SVD was the strongest correlate of overall mortality (hazard ratio=7.7; 95% CI, 4.4-13.6). CONCLUSIONS: Early SVD is frequent in Mitroflow bioprosthesis (models 12A/LX), especially for small sizes (19 and 21 mm), and reduces overall survival. An unpredictable accelerated pattern of SVD constitutes a life-threatening condition. In view of the large number of Mitroflow valves implanted worldwide, one can expect an epidemic of SVD and valve-related deaths, which represents a major public health issue, especially in the elderly. Hence, a close follow-up with yearly echocardiography after Mitroflow implantation is advisable. An urgent reoperation should be discussed in patients with severe SVD even though they are still asymptomatic.