Luc-Marie Jacquet

Effects of conventional physiotherapy, continuous positive airway pressure and non‐invasive ventilatory support with bilevel positive airway pressure after coronary artery bypass grafting

Background: Coronary artery bypass graft (CABG) surgery with the use of mammary arteries is associated with severe alteration of lung function parameters. The purpose of the present study was to compare the effect on lung function tests of conventional physiotherapy using incentive spirometry (IS) with non‐invasive ventilation on continuous positive airway pressure (CPAP) and with non‐invasive ventilation on bilevel positive airway pressure (BiPAP or NIV‐2P).

Cardiac troponin I as an early marker of myocardial damage after coronary bypass surgery

STUDY OBJECTIVE To evaluate the performance of cardiac specific markers, cardiac troponin I (cTnI) and CK-MB by mass assay (CK-MB mass), for the early diagnosis of myocardial ischemia and/or infarction after coronary bypass surgery. METHODS Prospective clinical, electrocardiograpic and biologic follow-up of 117 patients undergoing isolated coronary surgery with the use of intermittent anterograde normothermic blood cardioplegia. Blood samples for biochemical analysis were drawn before surgery (T0) and at 2 (T1), 6 (T2), 10 (T3) and 20 h (T4) after aortic cross-clamp release. Without knowledge of the biochemical data, patients were classified according to the electrocardiographic evolution into two groups: group 1, uneventful recovery and group 2, evidence of ischemia/infarction based on continuous ST-T segment monitoring and 12-lead ECG. RESULTS No patients had abnormal markers at T0. At T1, although both markers were elevated, no difference was noted between the two groups. At T2, 6 h after surgery, cTnI and CK-MB mass levels were significantly higher in group 2 than in group 1 (median = 17 microg/l, Interquartile Range (IR): 14.7-27.3 vs. 3.1 microg/l, IR 1.9-5.3 for cTnI and median 42.5 microg/l, IR: 27.1-95.7 vs. 13.6 microg/l, IR: 9.5-18.5 for CK-MB mass). A receiver operating characteristic (ROC) curve analysis shows that a cTnI value of 13.1 microg/ml has 100% specificity and 90% sensitivity to separate both groups, whereas a value of 33.2 microg/ml for CK-MB mass has a specificity of 100% and a sensitivity of 73%. At T3 and T4, the same difference was noted between the groups. cTnI values in all six patients with a Q-wave infarction were > or = 20 ng/ml, whereas only one of five patients with prolonged ischemia had cTnI level > 20 ng/ml. CONCLUSION As soon as 6 h postoperatively, cTnI and CK-MB by mass assay were able to separate those patients with an uneventful recovery from those with significant ischemia. This is particularly useful in frequent cases when the ECG is difficult to interpret.

Analysis of the accuracy of continuous thermodilution cardiac output .measurement Comparison with intermittent thermodilution and Fick cardiac output measurement

ObjectiveTo evaluate the accuracy of cardiac output measurement obtained by a new continuous thermodilution cardiac output (CCO) pulmonary artery catheter compared to intermittent thermodilution (TCO) and the direct Fick method.DesignProspective open trial.SettingUniversity hospital, intensive care unit.Patients23 patients (15 surgical, 8 non-surgical) were monitored with the Intellicath pulmonary catheter. Cardiac output was evaluated by the three methods every 4 to 6 h as long as the pulmonary artery catheter was necessary (8–96h).ResultsThe correlation coefficient between CCO and TCO was 0.92, no systematic bias was observed, and the relative error increased from 13.9% for a cardiac output of 1 l/min to 23.7% for an output of 10 l/min. When comparing CCO and Fick, the correlation coefficient was 0.89, no bias was detected, and the relative error increased from 20.4% for outputs of 2 l/min to 27.2% for outputs of 10 l/min.ConclusionsCCO provides clinically acceptable measurements. At high cardiac outputs, the difference with other methods increases and the results must be cautiously interpreted.

Effects of normothermia versus hypothermia on extravascular lung water and serum cytokines during cardiopulmonary bypass : A randomized, controlled trial

ObjectiveTo evaluate the influence of perfusion temperature on the systemic effects of cardiopulmonary bypass (CPB), including extravascular lung water index (EVLWI), and serum cytokines. DesignProspective, randomized, controlled study. SettingCardiothoracic intensive care unit of a university hospital. PatientsPatients undergoing elective coronary artery bypass grafting. InterventionsTwenty-one patients undergoing elective coronary artery bypass grafting were randomly assigned to receive either normothermic bypass (36°C, n = 8) with intermittent antegrade warm blood cardioplegia (IAWBC), or hypothermic (32°C, n = 13) CPB with cold crystalloid cardioplegia. Measurements and Main Results Mean arterial pressure, heart rate, cardiac output, systemic vascular resistance, mean pulmonary arterial pressure, and pulmonary vascular resistance were determined at baseline, i.e., after induction of anesthesia but before sternal opening (T−1), at arrival in the intensive care unit (T0), and 4 hrs (T4), 8 hrs (T8), and 24 hrs (T24) after surgery. EVLWI, intrathoracic blood volume index (ITBVI), and EVLW/ITBV ratio were obtained by using thermal dye dilution utilizing an arterial thermistor-tipped fiberoptic catheter and were recorded at T−1, T0, T4, T8, and T24. Serial blood samples for cytokine measurements were obtained at each hemodynamic measurement time point. Before, during, and after CPB, there were no differences in the conventional hemodynamic measurements between the groups. There were no changes in EVLWI up to T8 in either group. Furthermore, no change in the ratio EVLW/ITBW was observed between the groups at any time, further indicating the absence of a change in pulmonary permeability. Plasma levels of interleukin-6, tumor necrosis factor-&agr;, and interleukin-10 increased during and after CPB, independently of the perfusion temperature. ConclusionNormothermic CPB is not associated with additional inflammatory and related systemic adverse effects regarding cytokine production and EVLWI as compared with mild hypothermia. The potential temperature-dependent release of cytokines and subsequent inflammation has not been observed and normothermic CPB may be seen as a safe technique regarding this issue.

Use of the right gastroepiploic artery as a coronary artery bypass graft in 307 patients.

From October 1988 to October 1995 the right gastroepiploic artery was used as a conduit for coronary surgery in 307 patients. Their average age was 56.5 years (range 25-75) and 274 patients (89%) were male. Twenty-six cases (8.5%) were re-operations and 58 patients (19%) were operated upon on an urgent or semi-urgent basis. Target coronary vessels were the right coronary artery and its branches in 280 cases (91.4%), the circumflex artery in 25 cases (8%) and the left anterior descending artery in two cases. The right gastroepiploic artery was used as an in situ graft in 303 cases (98.7%) and as a free graft in 4 (1.3%). A total of 291 patients (94.8%) also received at least one mammary artery graft: both mammary arteries were used in 167 patients (54.4%). An average of 3.6 distal anastomoses were made per patient, three of them with arterial grafts. Eleven (3.2%) right gastroepiploic artery grafts were doubled with saphenous vein intraoperatively because of persistent myocardial ischemia. In-hospital mortality was 1.6% (five patients). Perioperative myocardial infarction occurred in twelve patients (3.9%). Follow-up now averages 26 months (range 6-88). There have been five late deaths (1.6%). A total of 265 (89.2%) patients are angina free. Of the total, 145 patients have been investigated with a maximal-stress test coupled with scintigraphy: residual myocardial ischemia was found in 10 patients, right gastroepiploic artery was related in three. Ninety-six patients have undergone angiographic restudy at a mean of 12 months (range 8-88) postoperatively. Patency of the right gastroepiploic artery grafts was 91.8%. This study confirms that the right gastroepiploic artery can be used as a conduit for coronary artery bypass surgery with minimal mortality or morbidity. Mid-term patency rates and clinical outcome are encouraging.

Fibrinogen concentration significantly decreases after on-pump versus off-pump coronary artery bypass surgery: a systematic point-of-care ROTEM analysis

OBJECTIVES Studies have emphasized the importance of normal fibrinogen concentrations in surgical patients. The primary hypothesis of this study was that fibrinogen levels significantly decrease in on-pump coronary artery bypass graft (CABG) surgery versus off-pump coronary artery bypass graft (OPCAB) surgery. The second objective was to show that ROTEM (TEM International, GmbH, Munich, Germany) rapidly detects these abnormalities compared with standard tests. DESIGN A prospective, nonrandomized study. SETTING A university hospital. PARTICIPANTS Forty-two and 62 patients in the CABG and OPCAB groups, respectively, undergoing first-time bypass surgery were included. INTERVENTIONS CABG versus OPCAB surgery. MEASUREMENTS AND MAIN RESULTS Routine coagulation tests and ROTEM values were measured before anesthesia (T0), after the first dose of heparin (T1), after protamine (T2), upon intensive care unit arrival (T3), and 4 hours postoperatively (T4). The outcome measures were followed until 4 hours postoperatively. Fibrinogen concentrations were significantly lower in the CABG versus the OPCAB group at T2 (170 ± 44 v 243 ± 73 mg/dL, p < 0.001) and T3 (179 ± 42 v 232 ± 68 mg/dL, p < 0.001). This was confirmed by significantly lower FIBTEM maximal clot firmness values at T2 (9 ± 4 v 14 ± 5 mm, p < 0.001) and T3 (9 ± 4 v 13 ± 6 mm, p < 0.001). In the CABG group, patients received significantly more transfusions of all blood products except fresh frozen plasma. CONCLUSIONS Fibrinogen concentration significantly decreases after cardiopulmonary bypass. ROTEM helps in its fast detection.

Acute cardiac failure after sunitinib

A 54-year-old male with cytokine-refractory metastatic renal cell carcinoma was admitted because of respiratory distress and hypotension. Five years earlier, he has been treated with alpha interferon (IFN) and interleukin-2 (two cycles of 6 weeks, s.c.) for bone, mediastinal lymph node and pulmonary metastases. Six months before admission, sunitinib (50 mg/day during 4 weeks followed by 2 weeks of rest) was initiated for disease progression and a partial response (according to Response Evaluation Criteria in Solid Tumors criteria) was obtained after 3 months. Sunitinib was well tolerated with a grade 2 fatigue (NCI—CTC version 2). As cardiovascular risks, only a well-controlled chronic hypertension (carvedilol 25 mg/day) was recorded and sunitinib did not worsen blood pressure. He did not have symptoms or past medical history of ischemic cardiomyopathy. At admission, the patient was still taking sunitinib. The symptoms appeared 1 week before and worsened gradually. Blood pressure was 75/48 mmHg and heart rate 104 beats per minute. The patient was admitted into the intensive care unit. Chest radiograph revealed diffuse interstitial pulmonary infiltrates consistent with pulmonary edema. ECG demonstrated ST-segment elevation in aVR, T-wave inversion and ST-segment depression in D1, aVL, V5 and V6. Cardiac enzymes were abnormal: CPK, 643 IU/l (normal value <400); myocardial band, 10 mg/l (normal value <3) and Troponin-I, 2 ng/ml (normal value <0.06). Echocardiogram showed left and right ventricular dilatation. Hemodynamic data on admission showed biventricular failure (cardiac index 1.3 l/min/m, capillary wedge pressure 10 mmHg, pulmonary artery mean pressure 17 mmHg and right atrial pressure 17 mmHg) with a predominantly right ventricular dysfunction. Dobutamine infusion did not improve the hemodynamic status (after 12 h infusion at 10 c/kg/min, cardiac index remains at 1.27 l/min/m) as well as Milrinone. This situation was thus consistent with refractory heart failure. Eight days after admission, despite optimal cardiac and respiratory supports, he died from cardiac and respiratory failure with renal and liver dysfunctions. Post-mortem examination revealed a heart that was soft with mildly dilated atrial and ventricular chambers. The coronary arteries were normal with neither luminal narrowing nor thrombosis. No macroscopic or microscopic sign of myocardial ischemia or infarction was found. The valves were normal. The pericardium was highly fibrous and adhered to the epicardium. Three metastases were found in the lungs. The lower pole of the right kidney contained a metastatic nodule. At histology, the heart revealed a diffuse loss of cellular mass (Figure 1). The myocardial muscle bundles were fragmented and dissected by loose fibrous tissue in association with edema depleted of lymphocytic infiltration. The cytoplasm of myocardial cells was observed to be occasionally eosinophilic or vacuolized with gross anisokaryosis. These histological and cytological changes in the absence of inflammatory infiltrate were in favor of a cardiomyopathy of toxic origin. Vascular endothelial growth factor (VEGF) has been incriminated in angiogenesis and revascularization after myocardial infarction indicating that VEGF could be an important growth factor for the cardiac tissue [1]. In addition, platelet-derived growth factor receptors (PDGFR) are also expressed on cardiomyocytes. Cardiotoxicity, however, has been rarely described with antiangiogenic therapy [2, 3]. Sunitinib is a tyrosine kinase inhibitor with a wide range of kinase inhibition, including KIT, PDGFRa/b, VEGF receptor 1–3, colony-stimulating factor 1, RET and FLT3. Sunitinib improves progression-free survival in metastatic renal cell carcinoma and imatinib-refractory gastrointestinal stroma tumors (GISTs) [2, 3]. In a large phase III trial randomizing renal cell carcinoma patients between IFN or sunitinib, decline in left ventricular ejection fraction (any grade) has been observed in 10% of sunitinib-treated patients [2]. Among them, only 2% had a grade 3 cardiotoxicity. This frequency was not statistically different than the one observed in the IFN group and all the patients recovered without sequelae. In the randomized trial comparing placebo versus sunitinib in imatinib-resistant GIST, cardiotoxicity was not found to be increased by sunitinib [3] although the prescribing information for sunitinib mentions that 11% of patients had declines in LVEF to below the lower limit of normal in this last study [4]. Two other cases of cardiac failure were identified in sunitinib dose-escalation study in acute myeloid leukemia patients [5]. One of these patients received a high daily dosage (75 mg, 4 weeks followed by 2 weeks of rest) and the other developed cardiac deficiency after myocardial infarction. Recently, Chu et al. [6] assessed the cardiovascular risk associated with sunitinib in 75 patients with GIST. Six patients (8%) had a nonfatal New York Heart Association class III–IV congestive heart failure. Left and ventricular dysfunction improved in five of these patients after sunitinib discontinuation. Mechanisms of cardiac dysfunction is incompletely understood [7] but has been recently investigated by the same group. Interestingly, they found that sunitinib had direct cardiomyocyte toxicity and induced mitochondrial injury in mice [6]. Incubation of rat le tt e r to

Outcome of cardiac surgery patients with complicated intensive care unit stay.

Risk stratification has become an essential element in the practice of cardiac surgery. Several studies have identified preoperative risk factors for adverse outcome. However, outcome is mostly defined by 30-day mortality and morbidity. These data reflect poorly the benefit for the patient. Long-term survival, quality of life, and functional status should be included in a more global analysis of the outcome, particularly in patients with complicated ICU stay. By reviewing the recent data reported in the literature, we can identify a number of preoperative predictive factors for complicated ICU stay, including advanced age, chronic obstructive pulmonary disease, preoperative low ejection fraction, previous myocardial infarction, reoperation, renal failure, combined surgery (coronary artery bypass grafting plus valve surgery), low hematocrit, and neurologic impairment. Short- and long-term outcomes are dependent on the type of postoperative complication. Unfortunately, data regarding the long-term outcome in these situations are very scarce.

Allosensitization in bridge to transplant Novacor left ventricular assist device patients: analysis of long-term outcomes with regard to acute rejection and chronic allograft vasculopathy §

BACKGROUND The true relevance of allosensitization in patients benefiting from left ventricular assist device (LVAD) as bridge to transplant (BTT) is still debated. Available registry data referred to numerous devices precluding LVAD-specific analysis. Therefore, we studied all patients with Novacor LVAD prior to transplantation. METHODS From 1985 to 2006, 37 Novacor LVADs were implanted as BTT, with 30 patients surviving to transplantation (81%). Post-LVAD sensitization was determined for anti-HLA-class I and class II IgGs. Study endpoints were overall survival and/or graft loss, > or =3A cellular rejection and chronic allograft vasculopathy (CAV). The results from LVAD patients were compared to non-LVAD primary heart transplant recipients (n=318). RESULTS After LVAD insertion, 5 out of 27 patients available for analysis developed anti-HLA antibodies (18.5%). The mean anti-HLA titer after Novacor LVAD implantation was 14% [SD 31]. Actuarial 5- and 10-year patient/graft survival for LVAD and non-LVAD transplant recipients were 73% and 55%, and 70% and 55%, respectively (p=NS). Overall prevalence of rejection > or =3A was 23.3 % (LVAD group) and 18.9% (non-LVAD group) (p=NS). At follow-up, the respective incidence of CAV was 8% (LVAD group) and 32.4% (non-LVAD group) (p<0.01). However, mean follow-up was significantly different for LVAD and non-LVAD patients, 46 vs 90 months (p<0.001). CONCLUSION In this study, allosensitization occurred infrequently after Novacor LVAD implantation. Secondly, analysis of outcome variables shows that Novacor-LVAD BTT patients can anticipate similar survival to non-LVAD patients, thus minimizing the impact of allosensitization after LVAD implantation.

Resection of the ascending aorta and aortic valve patch closure for type A aortic dissection after Novacor LVAD insertion.

A 60-year-old patient developed an acute type A aortic dissection in the postoperative course of a Novacor left ventricular assist device. We performed a resection of the ascending aorta with an aortic valve patch closure, end-to-end anastomosis of the outflow graft to the distal ascending aorta and two venous grafts to the coronary arteries, in order to avoid residual aortic insufficiency and bleeding related to exposure of the fragilized tissues to high pressures.