Gianpaolo Romano

Preoperative anemia in patients undergoing coronary artery bypass grafting predicts acute kidney injury

OBJECTIVES Recent authoritative studies suggested that low preoperative hemoglobin concentration may affect cardiac surgery outcomes. This study aimed, primarily, to investigate whether preoperative anemia is an independent determinant of adverse events after coronary artery bypass grafting and, secondarily, to evaluate the potential dose responsiveness between anemia severity and primary end points. METHODS This single-center prospective study investigated 1214 consecutive patients undergoing coronary artery bypass grafting between January 2004 and June 2007, collecting 100 variables per patient. In 1047 patients (median age 64 years, 18.8% female, 38.9% diabetic, 31.9% urgent/emergency, 15.3% with low preoperative left ventricular ejection fraction) who underwent on-pump procedures and received no preoperative transfusion, the prevalence of preoperative anemia (according to World Health Organization definition) and its unadjusted and adjusted relationships with in-hospital death, cardiac morbidity, and acute kidney injury (AKI-RIFLE [Risk, Injury, Failure, Loss, End-stage kidney disease] criteria) were obtained. RESULTS The prevalence of preoperative anemia was 28%. In-hospital death averaged 3.9%, cardiac morbidity 7.3%, and acute kidney injury 4%. Unadjusted odds ratios (Ors) for in-hospital death, cardiac morbidity, and acute kidney injury were 3.8 (95% confidence interval [CI] 2.0-7.3), 1.7 (95% CI 1.1-2.8), and 4.0 (95% CI 2.1-7.6), respectively. Adjusting for anemia in confounders proved an independent predictor of acute kidney injury (OR 2.06; 95% CI 1.14-3.70), whereas the cardiac morbidity and in-hospital mortality were independently predicted by kidney function. No dose-response relationship emerged between anemia severity and acute kidney injury. CONCLUSIONS Preoperative anemia is independently associated with acute kidney injury after coronary artery bypass grafting. Further studies are warranted to determine whether preoperative low hemoglobin concentration is a marker of severity of illness or a modifiable risk factor.

CD117‐Positive Cells in Adult Human Heart Are Localized in the Subepicardium, and Their Activation Is Associated with Laminin‐1 and α6 Integrin Expression

CD117‐positive cells contributing to cardiac cell turnover in normal and pathological conditions have recently been described in adult human heart. Since the precise spatial and temporal expression of extracellular matrix proteins and their receptors is critical for organ formation, we compared the distribution of cardiac primitive CD117‐positive cells in the human adult normal and pathological hearts with ischemic cardiomyopathy, with respect to localization and expression of laminin and integrin isoforms. In the pathological hearts, CD117‐positive cells were significantly more numerous than in the normal hearts. They were localized mainly in the atria and were up to 38‐fold more numerous in the subepicardium than in the myocardium. Compared with normal hearts, most CD117‐positive cells in the subepicardium of pathological hearts were α6 integrin‐positive. Laminin‐1, typical of developing heart, was found predominantly in the subepicardium of adult heart. Immunoblotting revealed its highest expression in the normal atrium and pathological left ventricle. Both laminin isoforms reduced apoptosis and increased proliferation and migration of CD117‐positive cells in vitro with respect to control, but the effects of laminin‐1 significantly outweighed those of laminin‐2. Signaling mediated by α6 integrin was implicated in the migration and protection from apoptosis, as documented by transfection with specific small interfering RNA. These data reveal that the increase in the number of cardiac CD117‐positive cells and the expression of laminin‐1 are observed in ischemic cardiomyopathy. Subepicardial localization of CD117‐positive cells and expression of laminin‐1 and α6 integrin subunits may all correspond to the activation of regeneration involving an epithelial‐mesenchymal transition recently described in adult heart.

Recurrent infective endocarditis: a multivariate analysis of 21 years of experience

BACKGROUND To evaluate which variables predict recurrence of endocarditis after surgical treatment, we reviewed our 21-year experience. METHODS Between January 1979 and May 2000, 308 consecutive valve replacement procedures for infective endocarditis were performed in 271 patients. Univariate and multivariate time-related analyses were performed to retrospectively evaluate the role of the following variables in the development of recurrent postoperative endocarditis: gender, site of endocarditis, previous valve disease, drug abuse, diabetes, positive valve/blood cultures, sepsis, perivalvular involvement, previous embolic events, type of replacement device, and persistent postoperative fever. RESULTS Clinical and echocardiographic follow-up was 97.36% complete, mean follow-up time was 53.2+/-3.4 months. Recurrent endocarditis developed in 58 cases (22.5%). Variables predicting recurrence were prosthetic endocarditis (p = 0.00001), positive valve culture (p = 0.0039), and persistence of fever at the seventh postoperative day (p = 0.000001). CONCLUSIONS Correct protocols of antibiotic therapy guided by microbiology may reduce the incidence of recurrent endocarditis to allow for surgery on sterile tissues and to prevent prosthetic infection. Recurrence rate is not affected by the choice of valve substitute, but can be prevented by complete surgical debridement.

Mechanical Aortic Valve Replacement in Young Women Planning on Pregnancy : Maternal and Fetal Outcomes Under Low Oral Anticoagulation, a Pilot Observational Study on a Comprehensive Pre-Operative Counseling Protocol

OBJECTIVES This pilot prospective observational study aimed to evaluate the maternal and fetal outcomes of pregnancies under low-dose oral anticoagulation therapy after aortic mechanical replacement. BACKGROUND Need for valve replacement is still an issue for young women with native valve disease who are planning on future pregnancy. Choice of replacement device is a challenging clinical task. METHODS A comprehensive pre-operative counseling protocol to guide choice of replacement device was developed. The pre-operative anticoagulation trial to determine the warfarin daily dosage needed to reach target international normalized ratio (INR) represented the main stem of such protocol. Pregnancies on low-dose anticoagulation therapy (target INR: 1.5 to 2.5) were allowed in a highly selected subset of mechanical aortic valve recipients. RESULTS Twenty-two patients of 40 originally referred for native valve disease surgery requiring valve replacement, safely underwent the pre-operative anticoagulation challenge. No maternal or fetal complications were detected in 16 pregnancies under low oral anticoagulation. Patterns of warfarin daily dosage and induced INRs were characterized during pregnancy. CONCLUSIONS In this small sample observational study, a pre-operative anticoagulation therapy trial helped young women scheduled for valve replacement to acquire complete information as to the choice of prosthetic device. In selected third-generation mechanical aortic prosthesis recipients, low-dose anticoagulation therapy seems safe and feasible for both mother and fetus. Further studies are needed to validate this approach.

Are blood and valve cultures predictive for long-term outcome following surgery for infective endocarditis?

OBJECTIVE To evaluate whether perioperative bacteria identification in blood and/or in valve cultures can predict early and late outcome of surgery for infective endocarditis, a retrospective study was performed. METHODS Between January 1978 and December 1998, 232 patients, 79 (34.1%) female and 153 (65.9%) male with mean age of 44. 95+/-1.03 years (range 8-79) underwent surgery for infective endocarditis on a native (162 cases) or prosthetic (70 cases) valve. Patients were divided into three groups according to the perioperative x of microbiological tests: Group A: patients with preoperative positive blood cultures (83 cases); Group B: patients with positive valve cultures (35 cases); Group C: patients with negative blood and valve cultures (114 cases). Categorical values were compared by chi(2) analysis, whereas continuous data were compared by ANOVA and Bonferroni correction for post hoc comparisons. Analysis of late survival and complications was performed with Kaplan-Meier and Log Rank test. Late mortality, reoperation, perivalvular leak, recurrence of infection were considered as treatment failure. All data were presented as mean+/-standard error. RESULTS Hospital mortality was 10.8% (9/83) in Group A, 8.6% (3/35) in Group B, and 14.9% (17/114) in Group C (P=0.52; not significant (NS)). Ten-year survival was 62.7+/-8% in Group A, 43.9+/-19% in Group B and 62.7+/-7% in Group C (P=0.38; NS). Ten-year freedom from reoperation was 85.2+/-6% in Group A, 37.9+/-20% in Group B and 80+/-6% in Group C (P=0.0034). Ten-year freedom from treatment failure was 56.3+/-8% in Group A, 31.6+/-16% in Group B and 55. 3+/-7% in Group C (P=0.46; NS). CONCLUSIONS Positive blood and tissue cultures are not predictive for hospital mortality and late treatment failure in patients with infective endocarditis. Positive valve cultures, a common finding in patients with staphylococcal endocarditis, are predictive for a higher risk of reoperation.

Leukoreduction program for red blood cell transfusions in coronary surgery: Association with reduced acute kidney injury and in-hospital mortality

OBJECTIVE Leukocytes in allogeneic blood transfusions cause several immunomodulatory events. This before-and-after cohort study evaluated clinical outcomes after adoption of prestorage leukoreduction program for blood transfusions, with particular focus on acute kidney injury. METHODS One thousand thirty-four consecutive patients who underwent on-pump coronary artery bypass grafting between January 2004 and December 2007 were included. Propensity score analysis for transfusion was performed in the whole population; patients who were actually transfused were then divided according to leukoreduction. From these 2 groups, 147 pairs matched for propensity score were considered to evaluate with bivariate and multivariable analyses the effects of leukoreduction, with all-cause in-hospital mortality and morbidity as main outcomes. RESULTS Unadjusted in-hospital mortalities were 6.6% for the entire cohort and 44.2% for those with acute kidney injury. In the matched population, after introduction of leukoreduction, mortality rates decreased to 5.4% (vs 11.4%) and acute kidney injury (RIFLE [Risk, Injury, Failure, Loss of function, End-stage renal disease] class R or greater) dropped from 51.7% to 41.5% (relative risk -20%, P < .045). No difference emerged regarding other major complications. At multivariable analysis, intra-aortic balloon pump, RIFLE score, and propensity score for transfusion proved independent predictors of in-hospital mortality. Intra-aortic balloon pump and nonleukodepleted transfusion emerged as independent predictors of acute kidney injury. Multivariable analysis on the overall cohort of transfused patients confirmed that nonleukodepleted transfusion was an independent predictor of acute kidney injury. CONCLUSIONS Leukoreduction of allogeneic blood products is associated with decreased acute kidney injury and mortality in highly transfused patients.

Microbiologically documented nosocomial infections after cardiac surgery: an 18-month prospective tertiary care centre report

OBJECTIVE The aim of this study was to prospectively evaluate frequency, characteristics, and predictors of nosocomial infections (NI) in a tertiary care centre. METHODS Study population included 925 patients (mean age 62.3+/-12.5, 32.3% females, 22.9% diabetics, 6.8% with previous cardiac procedures) operated on between June 2005 and December 2006 (CABG 48.72%, valvular procedures 30.05%, thoracic aortic 10.9%, heart transplantations 3.78% and miscellanea 6.55%, procedure status: elective 72.9%, urgent 15.9% and emergent 11.2%). The study population was divided in two groups according to development of NI. Primary endpoints were multiorgan failure (MOF) and hospital mortality in the two groups. Secondary endpoints were length of intubation, intensive care unit (ICU) stay and overall hospitalisation. Univariate and multivariate analysis of NI predictors was conducted between 115 perioperative variables. RESULTS Eighty-three patients (9%) developed a NI. Infections affected respiratory tract in 51.8%, blood stream in 20.5 and wound infection in 27.7 (13.3% deep wound). Staphylococcal species (60.6%) predominated in blood stream and surgical wound infections while Gram-negative species predominated in respiratory infections. Patients affected by NI experienced significantly higher incidence of MOF (12% vs 0.8%) and hospital mortality (24.1 vs 6.9%). Development of NI significantly lengthened all the steps of postoperative process of care (length of intubation: 49.9+/-73 h vs 19.1+/-35.2; ICU stay: 10.4+/-12.8 days vs 3.4+/-4.6 and hospitalisation 20.7+/-15.3 vs 10.6+/-7). Independent predictors of NI were immunosuppressive therapy [OR 12.9 (CI 5.07-31.2)], reintubation [OR 10.3 (CI 4.6-2.3)], stroke [OR 9.5 (CI 1.8-49)], resternotomy for bleeding [OR 6.7 (CI 1.9-23.6)], emergent/urgent status [OR 3.6 (CI 1.5-8.4)], CVVH [OR 3.2 (CI 1.4-7.5)] and length of intubation [OR 1.03 (CI 1.01-1.1)]. CONCLUSIONS NI still represents a serious complication. Presence of identified determinants of NI should prompt modification of management algorithms.

Implications of acute kidney injury after heart transplantation: what a surgeon should know

OBJECTIVE Data regarding risks and consequences of acute kidney injury (AKI) after cardiac transplantation are dismissingly few and unclear. This study defined the incidence, risk factors and prognostic implication of AKI in a single-center cohort operated on between January 1999 and December 2008. METHODS Data from 307 consecutive recipients (mean age: 47.42 ± 13.58, 20.5% female, 18.9% diabetics, 19.5% with previous cardiac operations, 26.4% hospitalized, 78.4 ± 33.7 ml min(-1) preoperative glomerular filtration rate (eGFR)) were analyzed using multivariable logistic regression modeling. AKI was defined according to RIFLE (Risk, Injury, and Failure; and Loss, and End-stage kidney disease) criteria. RESULTS RIFLE scores of I or F were detected in 14%, and continuous venovenous hemofiltration was needed in 6.1%. Risk factors for AKI were: previous cardiac operation (odds ratio (OR) 2.35; 95% confidence interval (CI), 1.11-4.9), blood transfusion (OR 1.08; 95% CI, 1.011-1.16), troponin I release >10 (OR 1.031; 95% CI, 1.001-1.064), length of ischemic time (OR 1.008; 95% CI, 1.011-1.16). Overall hospital mortality averaged 7.8% and overall 1-year mortality was 10.4%; both mortality rates increased with each RIFLE stratification (Normal 3.4%, RIFLE R = 7.1%; RIFLE I = 25.7%; and RIFLE F = 37.5% and Normal 5.6%, RIFLE R = 11.8%, RIFLE I = 25.7%, and RIFLE F = 37.5%, respectively). AKI proved independent predictors of both early and 1-year mortality. The burden of AKI significantly affected 1-year kidney function (Δ preoperative GFR-1-year GFR in AKI vs no AKI = -25.872 ± 22.54 vs -7.968 ± 34.18, p = 0.015). CONCLUSIONS AKI is a highly prevalent and prognostically important complication. Some of the risk factors for AKI identified may be modifiable.

Pulmonary artery hypertension in heart transplant recipients: how much is too much?

OBJECTIVES Unresponsive pulmonary hypertension (PH) may contraindicate heart transplant since it implies poor early outcomes. The present study reports the effectiveness of oral perioperative sildenafil in allowing heart transplant candidacy and surgery in a selected group of patients initially deemed ineligible because of PH. METHODS Between May 2005 and December 2009, 31 consecutive patients (5 females, 9 with a history of idiopatic cardiomyopathy and 16 with a history of coronary artery disease, 10 with previous sternotomies, 71.42 ± 27.69 ml/min/m(2) mean preoperative epidermal growth factor receptor) were qualified for oral sildenafil because of unresponsive PH at baseline right heart catheterization (RHC). After a 12-week trial, RHC disclosed PH reversibility (mean pulmonary vascular resistance index: 9.57 ± 4.07 WU, mean transpulmonary gradient 14.47 ± 5.66 mmHg and mean systolic pulmonary artery pressure: 68.96 ± 15.15 mmHg), allowing listing despite a higher risk for early post-transplant RV failure. Transplant protocol included donor/recipient size matching ≥ 0.8 and inhaled nitric oxide in the early postoperative period followed by reinstitution of oral sildenafil. RESULTS All patients underwent heart transplantation. Mean overall graft ischaemic time was 179 ± 47 min; mean donor recipient weight ratio was 1.04 ± 0.17. Right ventricular failure developed in three patients (9.6%) and hospital mortality was 3.2%. Protocol RHC disclosed pulmonary haemodynamic profile normalization within the third postoperative month allowing weaning from sildenafil in the 30 hospital survivors. One-year RHC confirmed PH reversal (n = 29 patients, all who survived up to 1 year). CONCLUSIONS This pilot prospective uncontrolled trial suggests that oral sildenafil is effective in allowing candidacy, safe transplantation and postoperative pulmonary profile normalization in potential recipients initially disqualified because of PH.

Noninvasive positive-pressure ventilation for extubation failure after cardiac surgery: Pilot safety evaluation

OBJECTIVE Extubation failure is a serious complication after cardiac surgery. The role of noninvasive positive-pressure ventilation for acute respiratory failure in patients undergoing cardiac surgery is unknown. This study aimed to assess the safety of implementing noninvasive positive-pressure ventilation in this setting and its impact on lung function and operative outcomes. METHODS In a 6-month pilot prospective survey, the study population comprised 43 patients (32 were male with a mean age of 65.73 +/- 9 years; 3 heart transplantations, 18 coronary artery bypass grafts, 5 aortic dissections, and 17 valvular procedures; 34 active smokers, 25 with medically treated chronic obstructive pulmonary disease, 21 emergency/urgency procedures) who required noninvasive positive-pressure ventilation for acute respiratory failure after initial weaning from a respirator. The cause of acute respiratory failure (classified as post-cardiopulmonary bypass lung injury in 48.8% [21 patients], cardiogenic edema in 30.2% [13 patients], and pneumonia in 21% [9 patients]), length of noninvasive positive-pressure ventilation support, respiratory ratios (arterial oxygen tension/fraction of inspired oxygen assessed immediately before noninvasive positive-pressure ventilation, and every 6 hours after institution of pressure ventilation), and need for reintubation along with a set of predefined safety parameters were recorded. RESULTS The mean length of noninvasive positive-pressure ventilation support was 33.8 +/- 24.04 hours. Plotting respiratory ratios with length of noninvasive positive-pressure ventilation supports a significant improvement was already evident within the first 6-hour frame (133.6 +/- 39.5 vs 205 +/- 65.7; P < .001) for all causes. Noninvasive positive-pressure ventilation prevented intubation in 74.4% of the patients, with satisfactory recovery for post-cardiopulmonary bypass lung injury and cardiogenic dysfunction (90.5% and 69.2%, respectively) and poor results (55% reintubated) in those treated for pneumonia. Noninvasive positive-pressure ventilation safety approached 97.7%. CONCLUSION In appropriate candidates, noninvasive positive-pressure ventilation exerts favorable effects on lung function, preventing reintubation. The cost-effectiveness of its systematic use in this setting should be assessed.