Nicola Galdieri

Role of Sildenafil in Acute Posttransplant Right Ventricular Dysfunction: Successful Experience in 13 Consecutive Patients

BACKGROUND Superimposed acute right ventricular dysfunction in the setting of preexisting pulmonary hypertension is a nearly fatal complication after heart transplantation. The optimal treatment modality remains a matter of debate. Recently, sildenafil citrate, a nonselective pulmonary vasodilator, has gained popularity in the treatment of pulmonary hypertension in transplant candidates. METHODS Herein we have presented a series of 13 patients in whom sildenafil was used to treat right ventricular dysfunction and pulmonary hypertension as detected by transesophageal echocardiography and Swan-Ganz right heart catheterization after heart transplant. Their characteristics were mean age 49+/-11.4 years; 38.4% with previous cardiac procedures, 30.8% status I, basal pulmonary vascular resistance index 10.4+/-4.6 WoodU, mean transpulmonary gradient 18.7+/-5.4 mmHg. In addition to conventional inodilator support, we administered 1 to 3 mg per kilogram of sildenafil. Complete hemodynamic measurements were obtained before and after the institution of the therapy and at 1-month follow-up. RESULTS Within the first 72 hours, acute right ventricular dysfunction resolved in all cases without untoward side effects or significant systemic impact. Sildenafil significantly decreased the transpulmonary gradient and pulmonary vascular resistance index relative to baseline values; 5.6+/-1.82 versus 10.4+/-4.6 WU, (P< .05), 13.5+/-3.4 mm Hg versus 18.7+/-5.4 mm Hg (P< .05), respectively. Improved indices of right ventricular function were observed on echocardiographic monitoring. After 1 month, sildenafil treatment was discontinued. CONCLUSION Management of acute right ventricular dysfunction in heart transplant recipients with pulmonary hypertension using sildenafil proved safe and effective.

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.

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.

Surgical repair of acute type A aortic dissection: continuous pulmonary perfusion during retrograde cerebral perfusion prevents lung injury in a pilot study.

OBJECTIVE Postoperative respiratory failure is a frequent and serious complication in patients with type A acute aortic dissection operated on with deep systemic hypothermia. Interaction between neutrophils and pulmonary endothelium along with ischemic insult and reperfusion are the major determinants of lung injury. The aim of this prospective study was to evaluate the effect of continuous pulmonary perfusion during retrograde cerebral perfusion on lung function. METHODS Twenty-two patients referred for acute type A aortic dissection, who were free from preoperative respiratory dysfunction, were assigned prospectively and alternately to one of 2 treatment groups. Pulmonary perfusion was performed during retrograde cerebral perfusion in group B (11 patients), whereas the conventional Ueda technique was applied in group A (11 patients). Lung function was evaluated on the basis of intubation time, scoring of chest radiographs at 12 hours after cardiopulmonary bypass, and Pao(2)/fraction of inspired oxygen ratio assessed from immediately before the operation to 72 hours after termination of cardiopulmonary bypass. RESULTS Study groups were homogeneous for age, sex, interval between symptom onset and surgical operation, previous aortic surgery, preoperative ejection fraction and pulmonary gas exchange function, extent of aortic repair, and concomitant procedures. Cardiopulmonary bypass time, length of retrograde cerebral perfusion, operation time, need for blood substitutes, and surgical revision for bleeding did not differ between treatment groups. Postoperative Pao(2)/fraction of inspired oxygen ratios were higher in group B than in group A, and the difference remained statistically significant throughout the study period. The incidence of prolonged ventilator support (>72 hours) and the severity of the radiographic pulmonary infiltrate score were lower in the perfused group (18.2% vs 72.7% [P =.015] and 0.81 +/- 0.75 vs 1.8 +/- 0.78 [P =.028], respectively). CONCLUSIONS Continuous pulmonary perfusion provided a better preservation of lung function in patients operated on with deep systemic hypothermia.

Does priming implementation with low-dose albumin reduce postoperative bleeding following cardiopulmonary bypass?

This study aimed to assess whether low doses of albumin in the priming solution for cardiopulmonary bypass (CPB) reduce postoperative bleeding. Three-hundred and seventy-seven patients undergoing CPB were retrospectively assigned to group A (154 patients, CPB primed with 20 ml/kg Ringer Lactate solution + 0.75mg/kg albumin 20%) and group B (223 patients with 20 ml/kg Ringer Lactate). A significant difference was found in terms of reoperations for bleeding (group A 0/154 versus group B 9/223; P=0.033). The mean number of blood derivatives transfused per patient was higher in group B than in group A (p <0.001). Platelet count after CPB was higher in group A than in group B (175±52×103/μl versus 131±70×103/μl; P=0.045). The amount of postoperative bleeding was 525ml versus 680ml at 24hrs (p <0.001), 819ml versus 1102ml at 48hrs, (p <0.001), 963ml versus 1294ml at 72hrs, (p <0.045) (group A versus group B respectively). Crystalloid priming with low-dose albumin reduces postoperative bleeding.

Pattern of resolution of pulmonary hypertension, long‐term allograft right ventricular function, and exercise capacity in high‐risk heart transplant recipients listed under oral sildenafil

Unresponsive pulmonary hypertension (PH) implies poor posttransplant outcomes. Data on late adaptation of the right ventricle (RV) are still few. This study evaluated three‐yr RV function and remodeling, exercise capacity, and hemodynamic data in a selected group of patients initially disqualified because of PH. Between May 2005 and December 2009, 31 consecutive patients were qualified for oral sildenafil because of unresponsive PH at baseline right heart catheterization (RHC). After a 12‐wk trial, RHC disclosed PH reversibility (mean PVR: 5.41 ± 3 Wood units, mean TPG 14.5 ± 5.6 mmHg, and mean systolic PAP 68.9 ± 15.1 mmHg), allowing listing even though as high‐risk procedures. All patients underwent heart transplantation. RV failure developed in three patients (9.6%), and hospital mortality was 3.2%. Protocol RHC disclosed pulmonary hemodynamic profile normalization within the third postoperative month, allowing weaning from sildenafil in the 30 hospital survivors. One‐ and three‐yr RHCs confirmed stable PH reversal (n = 26, all three‐yr survivors). Parameters of late RV function and remodeling proved satisfactory. Parameters of functional capacity (Vo2 peak 19.7 ± 3.6 mL/kg/min and slope VE/Vco2 34.8 ± 2.7) proved homogeneous to those measured in transplant recipients with normal preoperative pulmonary artery pressure. Oral sildenafil is effective in allowing candidacy, safe transplantation, and long‐term survival in PH recipients initially disqualified.

Perioperative Myocardial Injury after Adult Heart Transplant: Determinants and Prognostic Value

Background and Aim of the Study Implications of Cardiac troponin (cTnI) release after cardiac transplantation are still unclear. This study disclosed risk factors and prognostic implication of cTnI early levels in a single centre cohort operated on between January 1999 and December 2010. Methods Data on 362 consecutive recipients (mean age: 47.8±13.7, 20.2% female, 18.2% diabetics, 22.1% with previous cardiac operations, 27.6% hospitalized, 84.9±29.4 ml/min preoperative glomerular filtration rate) were analyzed using multivariable logistic regression modeling. Target outcomes were determinants of troponin release, early graft failure (EGF), acute kidney injury (AKI) and operative death. Results Mean cTnI release measured 24 hours after transplant was 10.9±11.6 μg/L. Overall hospital mortality was 10.8%, EGF 10.5%, and AKI was 12.2%. cTnI release>10 μg/L proved an independent predictor of EGF (OR 2.2; 95% CI, 1.06–4.6) and AKI (OR 1.031; 95% CI, 1.001-1.064). EGF, in turn, proved a determinant of hospital mortality. Risk factors for cTnI>10 μg/L release were: status 2B (OR 0.35; 95% CI, 0.18-0.69, protective), duration of the ischemic period (OR 1.006; 95% CI, 1.001-1.011), previous cardiac operation (OR 2.9; 95% CI, 1.67-5.0), and left ventricular hypertrophy (OR 3.3; 95% CI, 1.9-5.6). Conclusions Myocardial enzyme leakage clearly emerged as an epiphenomenon of more complicated clinical course. The complex interplay between surgical procedure features, graft characteristics and recipient end-organ function highlights cTnI release as a risk marker of graft failure and acute kidney injury. The search for optimal myocardial preservation is still an issue.

Postoperative bleeding in coronary artery bypass patients on double antiplatelet therapy: predictive value of preoperative aggregometry

OBJECTIVES We tested the possible value of routine aggregometry testing for bleeding prediction following coronary artery bypass grafting in patients who received preoperative double antiplatelet therapy. METHODS In 226 patients undergoing on-pump isolated coronary artery bypass grafting, aggregometry [adenosine diphosphate (ADP) test and ASPI test] was always prospectively performed by Multiplate® analyser immediately before surgery. We assessed the differences in postoperative bleeding according to the type of double antiplatelet therapy [acetylsalicylic acid plus clopidogrel (ASA+C), or plus ticagrelor (ASA+T)], duration of clopidogrel/ticagrelor withdrawal (0-3 days or ≥ 4 days) and results of aggregometry tests. Multivariable predictors of blood losses were sought by linear regressions (drainage amount at 6, 12 and 24 postoperative hours) and logistic regression (increased bleeding: 75th percentile of blood losses at 6 h, i.e. >450 ml). RESULTS Overall, postoperative blood losses did not significantly differ between treatment groups (median at 6 h: ASA + C = 335 ml, ASA + T = 300 ml, P = 0.21). With longer withdrawal interval, higher rates of patients with normal ADP-related platelet function were observed in both groups (ASA + C: P = 0.04; ASA + T: P = 0.006) but only in the ASA + T group were blood losses significantly smaller at all 3 time points. Bleeders (>450 ml at 6 h) were significantly less frequent among patients with ADP test showing recovered platelet function (ASA + T: P = 0.002; ASA + C: P = 0.053). The correlation between ADP test result and blood losses amount was stronger in the ASA + T group (e.g. at 6 h: r = -0.6; P < 0.001). In multivariable analyses, the ADP test result independently predicted postoperative bleeding in the ASA + T group and the ASPI test in the ASA + C group. CONCLUSIONS Aggregometry can help in predicting postoperative bleeding in double antiplatelet therapy patients undergoing coronary artery bypass grafting.