Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin-induced thrombocytopenia-reactive antibodies or with true HIT (HIT-reactive antibodies plus thrombocytopenia): An 11-year experience.

Thrombocytopenia and thromboembolism(s) may develop in heparin immune-mediated thrombocytopenia (HIT) patients after reexposure to heparin. At the Onassis Cardiac Surgery Center, 530 out of 17,000 patients requiring heart surgery over an 11-year period underwent preoperative HIT assessment by ELISA and a three-point heparin-induced platelet aggregation assay (HIPAG). The screening identified 110 patients with HIT-reactive antibodies, out of which 46 were also thrombocytopenic (true HIT). Cardiac surgery was performed in HIT-positive patients under heparin anticoagulation and iloprost infusion. A control group of 118 HIT-negative patients received heparin but no iloprost during surgery. For the first 20 patients, the dose of iloprost diminishing the HIPAG test to ≤5% was determined prior to surgery by in vitro titration using the patients' own plasma and donor platelets. In parallel, the iloprost "target dose" was also established for each patient intraoperatively, but before heparin administration. Iloprost was infused initially at 3 ng/kg/mL and further adjusted intraoperatively, until ex vivo aggregation reached ≤5%. As a close correlation was observed between the "target dose" identified before surgery and that established intraoperatively, the remaining 90 patients were administered iloprost starting at the presurgery identified "target dose." This process significantly reduced the number of intraoperative HIPAG reassessments needed to determine the iloprost target dose, and reduced surgical time, while maintaining similar primary clinical outcomes to controls. Therefore, infusion of iloprost throughout surgery, under continuous titration, allows cardiac surgery to be undertaken safely using heparin, while avoiding life-threatening iloprost-induced hypotension in patients diagnosed with HIT-reactive antibodies or true HIT.

Clinical event rates with the On-X bileaflet mechanical heart valve: a multicenter experience with follow-up to 12 years.

OBJECTIVE: The aim of the study was to establish clinical event rates for the On-X bileaflet mechanical heart valve (On-X Life Technologies Inc, Austin, Tex) using an audit of data from the 3 centers within Europe with the longest history of implanting. METHODS: All patients receiving the On-X valve between March 1, 1998, and June 30, 2009, at 3 European centers were studied. Data were collected using questionnaire and telephone surveys augmented by outpatient visits and examination of clinical records. RESULTS: There were 691 patients, with a mean age of 60.3 years, who received 761 valves in total: 407 mitral valve replacements, 214 aortic valve replacements, and 70 aortic + mitral valve replacements (dual valve replacement). Total follow-up was 3595 patient-years, with a mean of 5.2 years (range, 0-12.6 years). Early (≤ 30 days) mortality was 5.4% (mitral valve replacement), 0.9% (aortic valve replacement), and 4.3% (dual valve replacement). Linearized late (>30 days) mortality expressed per patient-year was 3.6% (mitral valve replacement), 2.2% (aortic valve replacement), and 4.1% (dual valve replacement), of which valve-related mortality was 0.5% (mitral valve replacement), 0.2% (aortic valve replacement), and 1.8% (dual valve replacement). Late linearized thromboembolism rates were 1.0% (mitral valve replacement), 0.6% (aortic valve replacement), 1.8% (dual valve replacement). Bleeding rates were 1.0% (mitral valve replacement), 0.4% (aortic valve replacement), and 0.9% (dual valve replacement). Thrombosis rates were 0.1% (mitral valve replacement), 0% (aortic valve replacement), and 0.3% (dual valve replacement). Reoperation rates were 0.6% (mitral valve replacement), 0.2% (aortic valve replacement), and 1.2% (dual valve replacement). CONCLUSIONS: The On-X valve has low adverse clinical event rates in longer-term follow-up (mean 5.2 years and maximum 12.6 years).

Alterations in biomarkers of endothelial function following on-pump coronary artery revascularization.

BACKGROUND: Cardiopulmonary bypass (CPB) has been associated with activation and injury of endothelial cells, probably responsible for the systemic inflammatory response syndrome (SIRS) taking place in these patients. METHODS: We measured plasma concentrations of soluble P-selectin (sP-s), E-selectin (sE-s), tetranectin (TN), vonWillebrand factor (vWF) levels, and angiotensin-converting enzyme (ACE) activity in 31 adult patients undergoing elective coronary artery bypass grafting, just before and up to three days after surgery, and in 25 healthy volunteers. RESULTS: Patients showed higher plasma sP-s and sE-s and ACE concentrations, just before surgery, but significantly lower TN levels, compared with controls. During the first three postoperative days (PD), the concentration of each of the molecules followed a different and independent pattern, although in the third PD, the levels of sP-s, sE-s and ACE were higher and those of vWF and TN lower, compared with the preoperative ones. However, patients had higher sP-s (P=0.06), sE-s (P=0.07), and vWF (P=0.005), but lower TN concentrations (P=0.02) on the third PD compared with controls. CONCLUSIONS: CPB is characterised by pronounced changes in plasma sP-s, sE-s, TN, vWF levels, and ACE activity, which are associated with significant alteration in the intra- and early postoperative endothelial function observed in open heart surgery.

Aortic valve replacement: is there an implant size variation across Europe?

BACKGROUND AND AIMS OF THE STUDY: Prompted by anecdotal evidence and observations by surgeons, an investigation was undertaken into the potential differences in implanted aortic valve prosthesis sizes, during aortic valve replacement (AVR) procedures, between northern and southern European countries. METHODS: A multi-institutional, non-randomized, retrospective analysis was conducted among 2,932 patients who underwent AVR surgery at seven tertiary cardiac surgery centers throughout Europe. Demographic and perioperative variables including valve size and type, body surface area (BSA) and early mortality were collected. Group analysis by patient geographic distribution and by annular diameter of the prosthesis utilized was conducted. Patients with a manufacturer's labeled prosthesis size > or = 21 mm were assigned to the 'large' aortic size subset, while those with a prosthesis size < 21 mm were assigned to the 'small' aortic size subset. Effective orifice area indices were calculated for all patients to assess the geographic distribution of patient-prosthesis mismatch. Univariable and multivariable logistic regression analyses adjusting for possible confounding variables were performed. RESULTS: Prostheses with diameter < 21 mm were implanted at almost twice the rate in southern Europe compared to the north (56.4% versus 26.7%, p < 0.01). The mean valve size was also smaller in southern compared to northern European patients (21.6 +/- 2.1 mm versus 23.4 +/- 2.2 mm, p < 0.01). There were no regional differences in the distribution of either gender or BSA. In the multivariable model, south European patients were seven times more likely to receive a smaller-sized aortic valve (OR = 6.5, 95% CI = 4.82-8.83, p < 0.01), and thus the odds of developing patient-prosthesis mismatch were increased two-fold in southern European patients (OR = 1.9, 95% CI = 1.25-2.80, p = 0.02). However, neither geographic distribution nor valve size were significantly associated with operative mortality. CONCLUSION: The study results demonstrated differences in implanted aortic valve size, between the participating northern and southern European countries. Imbalances in the prevalence of rheumatic heart disease, health resource availability and variations in surgical practice throughout Europe might be possible etiological causes.

Gastrointestinal emergencies in cardiac surgery. A retrospective analysis of 3,724 consecutive patients from a single center.

OBJECTIVES: The aim of this study is to retrospectively analyze risk factors, diagnosis and management of gastrointestinal (GI) complications following cardiac operations. METHODS: Patients who developed GI complications after a cardiac operation were studied. Anesthesia protocols, techniques of cardiac surgery, potential risk factors, complications and medical and surgical interventions were reviewed and analyzed. RESULTS: Out of 3,724 consecutive patients undergoing heart operations during an 8-year period, 33 patients developed GI complications. Eleven patients developed ischemic colitis, 8 cholecystitis, 6 GI bleeding, 4 liver failures, 3 pancreatitis and 1 esophageal hernia. Patients with GI complications had a lower mean ejection fraction compared to patients not developing these complications (45.1 vs. 49.7%, p < 0.01). Also, patients undergoing an urgent cardiac operation were significantly more likely (3.49 times more likely) to develop GI complications postoperatively. Of the 33 affected patients, 18 were treated conservatively and 15 underwent an emergency exploratory laparotomy. Overall mortality was 12% (4 patients). CONCLUSIONS: Intestinal ischemia and cholecystitis appear to be the most frequent GI complications associated with cardiac surgery. Risk factors include a low ejection fraction and an urgent cardiac operation. Early recognition and treatment of these complications may reduce mortality.

Multicentered European study on safety and effectiveness of the On-X prosthetic heart valve: intermediate follow-up.

BACKGROUND: This study was performed to determine the safety and effectiveness of the On-X valve, a novel mechanical valve substitute. METHODS: Eleven centers participated in a European, multicentered, longitudinal, nonrandomized study of the On-X valve performance. Isolated aortic or mitral valve replacement with an On-X valve was studied in 301 patients. Aortic valve replacement was performed in 184 patients (average follow-up, 5.0 years), whereas mitral valve replacement was performed in 117 patients (average follow-up, 4.4 years). RESULTS: In patients with aortic valve replacement, mean transvalvular pressure gradients ranged from 8.3 to 4.7 mm Hg and effective orifice areas from 1.5 to 2.7 cm2, for 19-mm through 25-mm valves, respectively. After mitral valve replacement, mean gradient was 4.2 mm Hg and effective orifice area by pressure half-time was 2.6 cm2 regardless of valve size. Hemolysis was low, with postoperative serum lactate dehydrogenase at 225 +/- 41 IU (mean +/- standard deviation) or 253 +/- 65 IU, after aortic valve replacement or mitral valve replacement, respectively (upper normal value, 250 IU). At 1 year or greater postoperatively, 91.6% of patients after aortic valve replacement and 84.6% after mitral valve replacement were in New York Heart Association functional class I or II. Adverse event rates in percent per patient-year after aortic valve replacement or mitral valve replacement were thromboembolism, 0.88 or 1.76; thrombosis, 0.11 or 0.20; bleeding, 0.77 or 1.96, respectively. Late mortality was 1.97% or 2.55%, respectively. CONCLUSIONS: At the intermediate follow-up, the On-X valve exhibited improved hemodynamics, low hemolysis with in-range lactate dehydrogenase, and low adverse event rates, particularly in the aortic position.

Preoperative intravenous hydration confers renoprotection in patients with chronic kidney disease undergoing cardiac surgery.

Patients with chronic kidney disease (CKD) are at risk to develop acute renal failure (ARF) after open heart surgery. This complication is associated with high morbidity, mortality, and cost. Because the ability to concentrate urine is lost early in the progression of CKD, renal patients kept on fluid restriction prior to surgery may develop severe dehydration, a situation consistently found to be one of the most critical risk factors for postoperative ARF. Our goal was to investigate whether intravenous hydration for 12 h prior to cardiac surgery could prevent acute renal injury in patients with CKD. This is a prospective study in a tertiary cardiac surgery center. Forty-five patients admitted for elective open heart surgery with moderate-to-severe CKD, as evidenced by a quantified glomerular filtration rate less than 45 mL/min, were assigned using a 2/1 randomization process, to either receive an intravenous infusion of half-isotonic saline (1 mL/kg/h) for 12 h before the operation (hydration group, n = 30, 29 men, 64 + 1.7 years old), or to be simply kept on fluid restriction (control group, n = 15, 14 men, 64.2 + 2.8 years old). Groups were not different in clinical and intraoperative variables associated with postoperative renal injury. ARF developed in 8 of 15 (53%) patients in the control group, but in only 9 of the 30 (30%) patients in the hydration group. Four patients in the control group (27%), but no one in the hydration group, required dialysis after the operation (P < 0.01). Peak creatinine and blood urea nitrogen values were two to three times higher in the control group than in the hydration group. Preoperative intravenous hydration may ameliorate renal damage in patients with moderate-to-severe renal insufficiency undergoing cardiac surgery.

Effect of exogenous nitric oxide during cardiopulmonary bypass on lung postperfusion histology.

We tested the hypothesis that nitric oxide (NO) administered during cardiopulmonary bypass (CPB) would preserve platelets and prevent postperfusion lung changes. Ten anesthetized Yorkshire pigs were put on normothermic CPB (right atrium to aorta) with a roller pump and membrane oxygenator for 1 hour. In the study group (n = 5), NO was delivered in the oxygenator's gas inflow line with a MiniNO system at 5-10 ppm throughout CPB. In controls (n = 5), NO was not used. Crystalloid solution and norepinephrine were used to maintain blood pressure > or = 60 mm Hg. Fifteen minutes after CPB termination, all pigs were killed with intravenous potassium chloride and exsanguinated via the right atrium. Organ samples were put in formalin solution, processed in paraffin blocks, and stained with hematoxylin and eosin. We did not observe any thrombi in any perfusion system. There were no differences observed in platelet counts and aggregation ability to ADP and collagen, or in neutrophil counts between groups. Bleeding times were similar between groups before and after CPB. Also, there was no significant difference in factor XIIa and fibrinopeptide A levels between groups. Methemoglobin did not exceed normal levels. Lungs were devoid of neutrophils after perfusion in NO-treated pigs, whereas many neutrophils were present in the respiratory membrane of controls. Low-dose exogenous NO in the oxygenator's gas intake has no demonstrable effect on platelet number or function, but prevents neutrophil adhesion to lungs with a possible beneficial effect on postperfusion pulmonary morbidity.

Acute regional neuronal injury following hypothermic circulatory arrest in a porcine model.

OBJECTIVES: Although deep hypothermic circulatory arrest (HCA) is routinely used to interrupt normal perfusion of the brain and prevent subsequent cerebral ischemic injury during cardiac surgery, it is associated with various forms of neurologic disturbances. Neurologic sequelae after prolonged HCA include motor, memory and cognitive deficits. The present study was designed to assess acute regional neuronal injury after HCA in an animal model. METHODS: Six piglets underwent 75 min of HCA at 18 degrees C. Four piglets served as normal controls. After gradual rewarming and reperfusion, treatment animals were killed and their brains were perfusion-fixed and cryopreserved. Regional patterns of neuronal apoptosis after HCA was characterized by in situ DNA fragmentation using terminal deoxyneucleotidyl-transferase-mediated biotin-dUTP nick end-labeling (TUNEL) histochemistry. Hematoxylin and eosin histology was used to characterize cell damage morphologically. TUNEL-positive cells were scored on a scale of 0 to 5. Grade 0: no TUNEL-positive cells; Grade 1: <10%, Grade 2: 10-25%, Grade 3: 25-50%, Grade 4: 50-75%; and Grade 5: >75%. RESULTS: TUNEL-positive cells indicating DNA-fragmentation were scored in the precentral gyrus (motor neocortex), postcentral gyrus (sensory neocortex), hippocampus, cerebellum, thalamus and ventral medulla of HCA treated animals and were significantly greater than in normal controls (P

Clinical effectiveness of leukocyte filtration during cardiopulmonary bypass in patients with chronic obstructive pulmonary disease.

BACKGROUND: We tested the hypothesis that leukocyte filtration during pulmonary reperfusion preserves pulmonary function and results in improved oxygenation after cardiopulmonary bypass (CPB) in patients with chronic obstructive pulmonary disease (COPD). METHODS: In a prospective, randomized study, the treatment group consisted of 20 patients with COPD from consecutive open-heart procedures. A primed leukocyte filter was connected to the arterial line downstream of the standard arterial filter but was excluded from circulation. Circulated blood was directed through the leukocyte filter approximately 10 minutes before aortic cross-clamp removal and at early reperfusion for up to 30 minutes. These patients were compared to 20 additional COPD patients (controls) on whom systemic leukocyte filtration was not used during open-heart surgery. RESULTS: There was no significant difference in gender, age, left ventricular ejection fraction, type of procedure, aortic cross-clamp time, perfusion time, preoperative FEV1 and preoperative respiratory index (Pao2/FiO2 ratio) between treatment and control groups. The respiratory index changed in the treatment group by +9.8% of baseline after completion of CPB, by -14.2% upon arrival in the intensive care unit (ICU), and by -19.6% 12 hours later, whereas in the control group, it changed by -14.5% (p < 0.05), -27.7%, and -24%, respectively. Leukocyte-depleted patients required shorter intubation time (20.4 +/- 16.1 hours), ICU stay (46.2 +/- 40.1 hours) and length of hospitalization (8.3 +/- 2.8 days) than controls (29.5 +/- 21.9 hours, p < 0.05; 75.5 +/- 34.9 hours, p < 0.005; and 10.4 +/- 3.5 days, p < 0.05, respectively). Surgical (30-day) mortality was zero in both groups. CONCLUSIONS: In COPD patients having CPB, systemic leukocyte depletion at early reperfusion was associated with better oxygenation, shorter intubation time, and shorter ICU and hospital stays. Leukocyte filtration during CPB most likely preserves pulmonary function by ameliorating pulmonary reperfusion injury.

Neutrophil depletion reduces myocardial reperfusion morbidity.

BACKGROUND: We tested the hypothesis that depletion of neutrophil leukocytes from the cardioplegic and the initial myocardial reperfusion perfusates reduces clinical indices of reperfusion injury in patients undergoing elective coronary artery bypass. METHODS: We studied 160 consecutive patients who underwent standard coronary revascularization with cardiopulmonary bypass. Patients with recent myocardial infarction or coronary angioplasty were excluded. Cold blood cardioplegia was used. Just before aortic unclamping, the hearts were perfused retrograde with 250 mL of normothermic cardioplegic solution and 750 mL of blood (pump perfusate). Patients were randomly assigned to two groups. In 80 patients (treated), neutrophils and platelets were removed from all cardiac perfusate during aortic crossclamping with leukocyte filtration. In the remaining 80 patients (control group), leukocyte filtration was not used. RESULTS: There was no significant difference between groups in age, sex, severity of disease, and number of bypass grafts implanted. Treated patients showed lower prevalence of low cardiac index and reperfusion ventricular fibrillation and lower levels of creatinine kinase MB isoenzyme and troponin I early postoperatively (p < 0.05). CONCLUSIONS: Neutrophil-filtered blood cardioplegia/reperfusion significantly reduced clinical and biochemical indices of myocardial reperfusion injury after elective coronary revascularization with cardiopulmonary bypass.

Preoperative detection and management of immune heparin-induced thrombocytopenia in patients undergoing heart surgery with iloprost.

OBJECTIVE: The objective of this study was to evaluate our protocol for the identification and management of patients with immune heparin-induced thrombocytopenia undergoing cardiac surgery. METHODS: Among 1518 patients who underwent cardiac surgery between June 1998 and May 2001, 32 (2.1%) presented with platelet counts less than 150,000/mm3 preoperatively or a history of prolonged (>3 days) intravenous exposure to heparin or both. These 32 patients were evaluated with an enzyme-linked immunosorbent assay for antibodies against heparin-platelet factor 4 complex. Platelets of patients with detected antibodies were tested with the prostacyclin analog iloprost for inhibition of heparin aggregation and determination of the inhibiting concentration and corresponding intravenous infusion rate of iloprost. Patients with antibodies received heparin after complete platelet inhibition with iloprost infusion. Hypotension was prevented or treated with intravenous noradrenaline. Ten randomly selected patients with similar preoperative characteristics, no previous extended exposure to heparin, and normal platelet counts served as controls. RESULTS: Ten of the 32 patients (group A, 31.3%) and none of the controls had antibodies against heparin-platelet factor 4 complex. Patients in group A underwent surgery with iloprost (6-24 ng.kg(-1).min(-1)) and had their blood pressure maintained at greater than 95 mm Hg with norepinephrine infusion (1-4 microg.kg(-1).min(-1)). Operative mortality was zero. There were no thrombotic complications or bleeding requiring exploration. One patient in group A bled 1310 mL/6 hours but did not need exploration. There was no difference in postoperative blood loss and morbidity between groups. Platelet counts were reduced by 12.5% +/- 8.7% (group A) and 38.1% +/- 15.2% (control) (P <.001) 1 hour postoperatively and reached preoperative values by the fifth postoperative day. CONCLUSIONS: Immune heparin-induced thrombocytopenia can be detected preoperatively among patients with a low platelet count or a history of prolonged heparin exposure or both. Cardiac surgery can be safely undertaken using iloprost-induced platelet inhibition during heparinization.

Management of catheter-related injuries to the coronary sinus.

BACKGROUND: Although coronary sinus catheter-related injuries (CSCRIs) are rare, they are potentially lethal. The purpose of this study was to evaluate such injuries, the repair methods used, and to identify related risk factors for mortality. METHODS: A retrospective review of 10,552 cardiac surgical procedures from 1995 to 2000 in which retrograde cardioplegia was used revealed 10 cases (n = 10) of CSCRIs (0.095%) at our center. These injuries occurred during coronary bypass, valve replacement, and combined procedures. Management included direct suture, vein patch, or pericardial "on-lay" patch repair. RESULTS: Two deaths occurred (20% mortality) from failure of CSCRI repair; 8 of 10 injuries (80%) were successfully repaired. One patient had delayed, localized pericardial tamponade, which resolved spontaneously. Two patients had recurrent angina that was assessed 3 and 5 years later by coronary angiography; the coronary sinus was found to be patent in both cases. The remaining 6 patients have been asymptomatic. CONCLUSIONS: Repair of CSCRIs can be challenging as it can be complicated by inadequate myocardial protection, inadvertent coronary artery injuries, and possibly, subsequent coronary sinus thrombosis. Repair of CSCRIs should be carried out on an arrested, well-protected heart providing secure hemostasis and coronary sinus patency.

A prospective, double-blind study on the efficacy of the bioline surface-heparinized extracorporeal perfusion circuit.

BACKGROUND: We evaluated the newly introduced Bioline heparin coating and tested the hypothesis that surface heparinization limited to the oxygenator and the arterial filter will ameliorate systemic inflammation and preserve platelets during cardiopulmonary bypass (CPB). METHODS: In a prospective double-blind study, 159 patients underwent coronary revascularization using closed-system CPB with systemic heparinization, mild hypothermia (33 degrees C), a hollow-fiber oxygenator, and an arterial filter. The patients were randomly divided in three groups. In group A (controls, n = 51), surface heparinization was not used. In group B (n = 52), the extracorporeal circuits were totally surface-heparinized with Bioline coating. In group C (n = 56), surface heparinization was limited to oxygenator and arterial filter. RESULTS: No significant difference was noted in patient characteristics and operative data between groups. Operative (30-day) mortality was zero. Platelet counts dropped by 12.3% of pre-CPB value among controls at 15 minutes of CPB, but were preserved in groups B and C throughout perfusion (p = 0.0127). Platelet factor 4, plasmin-antiplasmin levels, and tumor necrosis factor-alpha increased more in controls during CPB than in groups B or C (p = 0.0443, p = 0.0238 and p = 0.0154 respectively). Beta-thromboglobulin, fibrinopeptide-A, prothrombin fragments 1 + 2, factor XIIa levels, bleeding times, blood loss, and transfusion requirements were similar between groups. Intensive care unit stay was shorter in groups B and C than in controls (p = 0.037). CONCLUSIONS: Surface heparinization with Bioline coating preserves platelets, ameliorates the inflammatory response and is associated with a reduced fibrinolytic activity during CPB. Surface heparinization limited to the oxygenator and the arterial filter had similar results as totally surface-heparinized circuits.

Safety and efficacy of off-pump coronary artery bypass grafting in chronic dialysis patients.

Off-pump coronary artery bypass grafting (CABG) has been recently revived, because cardiopulmonary bypass (CPB) appears to worsen the multiple organ dysfunction after conventional CABG. To evaluate the safety and efficacy of the off-pump CABG in chronic dialysis patients, we compared the perioperative morbidity and mortality between 15 dialysis patients who underwent off-pump CABG at our center over the past 8 years with that of a concurrent group of 19 patients who underwent conventional CABG. Patients were selected for off-pump CABG only when complete revascularization was technically feasible. We found that off-pump CABG is as safe and effective as conventional CABG in selected dialysis patients. It might even be beneficial, because it is associated with less hematocrit drop and blood product use, a lower catabolic rate, and fewer dialysis requirements after surgery. However, the impact of off-pump technique on the long-term clinical outcome and resource utilization in renal patients requires further investigation.

A new pattern for using both thoracic arteries to revascularize the entire heart: the pi-graft.

We present a complex graft for total arterial revascularization based on bilateral skeletonized internal thoracic arteries (ITA). The lower two-thirds of the free right ITA is anastomosed to the proximal segment of the left in situ ITA using the T-graft technique (Tector-Barner-Calafiore). The free, transected distal part of the left ITA is then anastomosed end-to-side on free right ITA (T-on-T anastomosis). In addition, the technique may use another graft extending the proximal third of the in situ right ITA with the free radial artery for right-sided revascularization. The entire operation can be performed off-pump to avoid any procedure on the ascending aorta.