Predictive scores for major bleeding after coronary artery bypass surgery in low operative risk patients.

BACKGROUND: Cardiac surgery is associated with perioperative bleeding and carries high risk of allogeneic blood transfusion. Recently new scores for prediction of severe bleeding have been developed. This study aims to compare the WILL-BLEED, CRUSADE, PAPWORTH, TRUST, TRACK and ACTION scores in predicting major bleeding after CABG in patients with low estimated operative risk. METHODS: A multicenter observational study included 1391 patients who underwent isolated CABG from July 2015 to January 2018. We tested the hypothesis that the WILL-BLEED score, specifically designed for CABG, would perform at least as well as the CRUSADE, PAPWORTH, TRUST, TRACK and ACTION scores in predicting postoperative major bleeding in low operative risk patients. The primary endpoint was the performance of known bleeding risk scores after CABG. The secondary endpoint was the evaluation of in-hospital mortality. RESULTS: Mean age was 68.2±9.4 years and median Euroscore II value was 1.69% (IQR 1.15-2.81%). Mean blood losses in the first 12 postoperative hours was 339.75 mL. Seventy-three (5.2%) subjects underwent administration of blood products. The rate of severe-massive bleeding according to UDPB grades 3-4 was 1.5%. WILL-BLEED, TRUST, TRACK and ACTION scores were significantly associated with severe postoperative bleeding. WILL-BLEED presented the best c-index (AUC: 0.658; 95% CI: 0.600,0.716). Reclassification analysis showed a worsening in sensitivity and significant negative reclassification of CRUSADE, PAPWORTH, TRACK and ACTION scores when compared with WILL-BEED. The combination of WILL-BLEED and TRUST scores improved the prediction ability (AUC: 0.673; 95% CI: 0.615-0.732). Overall in-hospital mortality was 1.65%. Early mortality in patients with severe versus no-severe bleeding was found to be 11.8% vs. 1.0% Severe bleeding (OR: 13.26; P value<0.001) was found to be significantly associated with early mortality. CONCLUSIONS: Severe bleeding after CABG is a harmful event associated with adverse outcomes. WILL-BLEED Score has the better performance in predicting severe-massive bleeding after CABG. The TRUST Score, although suboptimal, represents a valuable alternative in this setting.

Data regarding the effects of thrombin and dabigatran-inhibited thrombin on protease-activated receptor 1 and activation of human atrial fibroblasts.

The data presented here are related to the research paper entitled "Thrombin induces protease-activated receptor 1 signaling and activation of human atrial fibroblasts and dabigatran prevents these effects" (Altieri et al., 2018) [1]. Data show that silencing of protease-activated receptor 1 (PAR1) prevents the activation of Fib isolated from atrial appendages of patients without atrial fibrillation (AF), as assessed by immunofluorescence for α-smooth muscle actin (αSMA) and Picro-Sirius red staining. Moreover, it is reported that primary atrial Fib obtained from two subjects with permanent AF express PAR1 and PAR2 and display enhanced αSMA immunoreactivity and collagen synthesis in response to thrombin, but not to dabigatran-bound thrombin, alike Fib from non-fibrillating atria.

Thrombin induces protease-activated receptor 1 signaling and activation of human atrial fibroblasts and dabigatran prevents these effects.

BACKGROUND: Data with animal cells and models suggest that thrombin activates cardiac fibroblasts (Fib) to myofibroblasts (myoFib) via protease-activated receptor 1 (PAR1) cleavage, and in this way promotes adverse atrial remodeling and, thereby, atrial fibrillation (AF). OBJECTIVE: Here, we explored the effects of thrombin on human atrial Fib and whether they are antagonized by the clinically available direct thrombin inhibitor, dabigatran. METHODS: Fib isolated from atrial appendages of patients without AF undergoing elective cardiac surgery were evaluated for PAR expression and treated with thrombin with or without dabigatran. PAR1 cleavage, downstream signaling and myoFib markers were investigated by immunofluorescence and Western blot. Collagen synthesis, activity of matrix metalloprotease (MMP)-2 and proliferation were assessed by Picro-Sirius red staining, gelatinolytic zymography and BrdU incorporation, respectively. Fib function was studied as capability to contract a collagen gel and stimulate the chemotaxis of peripheral blood monocytes from healthy volunteers. RESULTS: Primary human atrial Fib expressed PAR1, while levels of the other PARs were very low. Thrombin triggered PAR1 cleavage and phosphorylation of ERK1/2, p38 and Akt, elicited a switch to myoFib enriched for αSMA, fibronectin and type I collagen, and induced paracrine/autocrine transforming growth factor beta-1, cyclooxygenase-2, endothelin-1 and chemokine (C-C motif) ligand 2 (CCL2); conversely, MMP-2 activity decreased. Thrombin-primed cells displayed enhanced proliferation, formed discrete collagen-containing cellular nodules, and stimulated the contraction of a collagen gel. Furthermore, their conditioned medium caused monocytes to migrate. All these effects were prevented by dabigatran. CONCLUSION: These results with human cells complete the knowledge about thrombin actions on cardiac Fib and strengthen the translational potential of the emerging paradigm that pharmacological blockade of thrombin may counteract molecular and cellular events underlying AF.

Aortic cross-clamp time and cardiopulmonary bypass time: prognostic implications in patients operated on for infective endocarditis.

OBJECTIVES: Prolonged aortic cross-clamp (XCT) and cardiopulmonary bypass time (CPBT) are associated with increased morbidity and mortality following cardiac surgery. The aim of this study was to assess the predictors of mortality and other severe postoperative complications in patients undergoing surgery for infective endocarditis (IE), focusing in particular on the role of prolonged XCT and CPBT. METHODS: A retrospective single-centre study was conducted from January 2000 to January 2017, including all patients undergoing valvular surgery for IE. The primary end point was early postoperative mortality. The main secondary end point was a composite end point for severe postoperative complications. RESULTS: During the study period, 264 patients were included. Early postoperative mortality was 14%. Prolonged CPBT [odds ratio (OR) 1.008, 95% confidence intervals (CIs) 1.003-1.01; P = 0.009] and increasing age (OR 1.04, 95% CI 1.01-1.07; P = 0.02) independently predicted mortality, while an inverse association was observed for left ventricular ejection fraction (OR 0.93, 95% CI 0.89-0.97; P = 0.0007). The best mortality cut-offs were >72 min for XCT and >166 min for CPBT. Prolonged CPBT also predicted severe complications, along with age, stroke, preoperative mechanical ventilation and reduced left ventricular ejection fraction. When XCT was included in the multivariable models instead of CPBT, it was associated with both mortality and severe complications. CONCLUSIONS: Prolonged XCT and CPBT are associated with mortality and development of severe complications after valvular surgery for IE. Further validation of safe limits for XCT and CPBT might provide novel insights on how to improve intraoperative and postoperative outcomes of patients with IE.

What is the Best Revascularization Strategy for Acute Occlusive Arterial Mesenteric Ischemia: Systematic Review and Meta-analysis.

PURPOSE: Acute mesenteric ischemia (AMI) is a life-threatening disease that leads to bowel infarction and death. The optimal management of AMI remains controversial. The present meta-analysis aimed to estimate the prognostic impact of surgical (SG) versus endovascular or hybrid intervention (EV) as the first-line treatment for acute arterial occlusive mesenteric ischemia and to assess whether endovascular strategy was actually effective in reducing bowel resection. METHODS: MEDLINE, Scopus and the Cochrane Library databases were searched. There have been no randomized controlled trials comparing SG versus EV for the treatment of AMI. We undertook this systematic review and meta-analysis according to MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines, assessing the included study quality with the Newcastle-Ottawa scale. RESULTS: Seven studies comparing EV versus SG as first strategy for the treatment of AMI were selected for the analyses, reporting of 3020 patients. EV was associated with a reduced risk of in-hospital mortality (RR 0.68; 95% CI 0.59-0.79; fixed-effects analysis; p < 0.0001; I 2 = 4.9%; τ 2 = 0.025). Pooled prevalence of mortality was 19% for EV and 34% for SG. EV also showed a benefit impact on risk of bowel resection and second-look laparotomy. CONCLUSIONS: The present meta-analysis outlines that endovascular revascularization strategy seems to offer advantages in terms of in-hospital mortality and morbidity in case of arterial occlusive AMI. A multidisciplinary team consisting of radiologists, interventional radiologists, cardiovascular and general surgeons comes out to be essential to tailor the right procedure to the patient and improve the outcomes associated with AMI.

RVAD Support in the Setting of Submassive Pulmonary Embolism.

Patients with submassive pulmonary embolism (PE), although normotensive, are characterized by right ventricular (RV) dysfunction and elevated levels of biomarkers of cardiac damage. The best treatment option in these cases is still a subject of debate and the use of thrombolysis in submassive PE remains controversial. A 57-year-old Caucasian male with unprovoked PE, normal blood pressure, and elevated troponin I values was referred to the cardiovascular department. In view of the presence of a right atrium thrombus, the patient underwent surgical embolectomy under extracorporeal circulation, with the extraction of a huge thrombus together with fragmented thrombi from both pulmonary arteries. The patient developed an acute right heart failure solved with a temporary RV assist device (RVAD) support. The RV recovery was observed after 72 hours following the implantation. RVAD placement should be considered in the management of PE in case of acute right heart failure after reperfusion therapy since it can bring the patient out of a death spiral.

Risk factors for infections due to carbapenem-resistant Klebsiella pneumoniae after open heart surgery.

OBJECTIVES: Patients undergoing major surgery are at increased risk of developing infections due to resistant organisms, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp). In this study, we assessed risk factors for CR-Kp infections after open heart surgery in a teaching hospital in northern Italy. METHODS: A retrospective study was conducted from January to December 2014. The primary outcome measure was postoperative CR-Kp infection, defined as a time-to-event end-point. The effect of potentially related variables was assessed by univariable and multivariable analyses. Secondary end-points were in-hospital mortality and 180-day postoperative mortality. RESULTS: Among 553 patients undergoing open heart surgery, 32 developed CR-Kp infections (6%). In the final multivariable model, CR-Kp colonization [hazard ratio (HR) 227.45, 95% confidence intervals (CI) 67.13-1225.20, P < 0.001], cardiopulmonary bypass time in minutes (HR 1.01, 95% CI 1.01-1.02, P < 0.001), chronic obstructive pulmonary disease (HR 3.99, 95% CI 1.61-9.45, P = 0.004), SOFA score (HR 1.29, 95% CI 1.08-1.53, P = 0.007), preoperative mechanical ventilation (HR 8.10, 95% CI 1.31-48.57, P = 0.026), prolonged mechanical ventilation (HR 2.48, 95% CI 1.08-6.15, P = 0.032) and female sex (HR 2.08, 95% CI 1.00-4.36, P = 0.049) were associated with the development of CR-Kp infection. Increased in-hospital mortality and 180-day mortality were observed in patients who developed CR-Kp infections in comparison with those who did not. CONCLUSIONS: In our cohort, CR-Kp colonization was an important predictor of CR-Kp infection after open heart surgery. CR-Kp infection after surgery significantly affected survival. Preventing colonization is conceivably the most effective current strategy to reduce the impact of CR-Kp.

Expectation and quality of life after aortic valve replacement over 85 years of age match those of the contemporary general population.

BACKGROUND: In the transcatheter aortic valve implantation (TAVI) years, very elderly patients with aortic stenosis (AS) are referred to surgery with reluctance despite excellent hospital outcomes. A poorly assessed outcome of discharged survivors might further overlook the actual efficacy of the surgical strategy in this cohort. We thus evaluated life-expectancy and functional results in discharged survivors over 85 years operated on for AS. METHODS: Between January 2001 and December 2013, 57 consecutive patients aged ≥85 years underwent aortic valve replacement (AVR) with or without concomitant procedures at our institution. Late survival rate (SR), New York Heart Associaion (NYHA) functional class and quality of life (RAND SF-36) were assessed. SR and quality of life (QoL) were than compared to the contemporary general population matched for age and gender, as calculated by the Italian National Institute of Statistics. RESULTS: Overall in-hospital mortality was 8.8% (5 pts). In patients without concomitant coronary artery bypass grafting (CABG), in-hospital mortality was 2.9%. Survival at 5 and 9 years was 57.7 ± 8.4% and 17.9 ± 11.4%, respectively. No predictors of late mortality including concomitant CABG were identified at Cox analysis. The mean NYHA class for long-term survivors improved from 3.1 to 1.6 (p<0.001). Survivors reported better QoL-scores compared to the age- and gender-matched contemporary general population in 4 RAND SF-36 domains. Life-expectancy resulted comparable to that predicted for the age and gender-matched general population. CONCLUSIONS: Isolated AVR in patients aged ≥85 years can be performed with acceptable risk. Survivors improve in NYHA class and, when compared to age- and gender-matched individuals, show a similar life expectancy and a no lower QoL.

Does patient-prosthesis mismatch after aortic valve replacement affect survival and quality of life in elderly patients?

BACKGROUND: To evaluate the impact of patient-prosthesis mismatch (PPM) on survival, functional status, and quality of life (QoL) after aortic valve replacement (AVR) with small prosthesis size in elderly patients. METHODS: Between January 2005 and December 2013, 152 patients with pure aortic stenosis, aged at least 75 years, underwent AVR, with a 19 or 21 mm prosthetic heart valve. PPM was defined as an indexed effective orifice area less than 0.85 cm/m. Median age was 82 years (range 75-93 years). Mean follow-up was 56 months (range 1-82 months) and was 98% complete. Late survival rate, New York Heart Association functional class, and QoL (RAND SF-36) were assessed. RESULTS: Overall, PPM was found in 78 patients (53.8%). Among them, 42 patients (29%) had an indexed effective orifice area less than 0.75 cm/m and 17 less than 0.65 cm/m (11.7%). Overall survival at 5 years was 78 ±â€Š4.5% and was not influenced by PPM (P = NS). The mean New York Heart Association class for long-term survivors with PPM improved from 3.0 to 1.7 (P < 0.001). QoL (physical functioning 45.18 ±â€Š11.35, energy/fatigue 49.36 ±â€Š8.64, emotional well being 58.84 ±â€Š15.44, social functioning 61.29 ±â€Š6.15) was similar to that of no-PPM patients (P = NS). CONCLUSION: PPM after AVR does not affect survival, functional status, and QoL in patients aged at least 75 years. Surgical procedures, often time-consuming, contemplated to prevent PPM, may therefore be not justified in this patient subgroup.