Capture of Particulate Emboli During Cardiac Procedures in Which Aortic Cross-Clamp Is Used

Transcription

1 Capture of Particulate Emboli During Cardiac Procedures in Which Aortic Cross-Clamp Is Used Wolfgang Harringer, MD, on behalf of the International Council of Emboli Management Study Group* Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany Background. Previous studies have shown that atheroemboli are associated with neurologic complications following cardiac operation. Additionally, it has been demonstrated that embolization is closely related to the application and removal of ascending aortic cross-clamps. Methods. A prospective registry of 304 patients was initiated to describe patient selection, procedures, particulate capture, and clinical outcomes after intraaortic filtration in patients undergoing cardiac surgical procedures with cardiopulmonary bypass and median sternotomy. Prior to the removal of the cross-clamp, the intraaortic filter (EMBOL-X Inc, Mountain View, CA) was deployed and left in place until the patient was weaned from extracorporeal circulation. Upon removal, filters were fixed in formalin and shipped to a core laboratory for examination. Results. Mean patient age was 68 years (range 25 to 88 years), 40% had ascending aortic calcification, 59% of the procedures were coronary artery bypass grafting (CABG), 20% were valve replacement or repair, and 12% were a combination of CABG and valve surgery. Aortic cross-clamps were used in nearly all cases (302 of 304 patients); partial clamps were used in 84% of the CABG procedures. To date, 243 filters have been examined. Sixty-two percent of the filters analyzed revealed fibrous atheroma, 2% grumous atheroma, and 6% epiaortic debris. Platelet and fibrin strands were found in 52% of the filters and 22% contained evidence of thrombus or red blood cells. Conclusions. These findings from the International Council of Emboli Management Registry confirm that particulates are released during cardiac surgical procedures using the aortic cross-clamp. Continued observational and randomized studies are necessary to confirm the clinical relevance of particulate extraction. (Ann Thorac Surg 2000;70: ) 2000 by The Society of Thoracic Surgeons Presented at the Sixth Annual Cardiothoracic Techniques and Technologies Meeting 2000, Ft Lauderdale, FL, Jan 27 29, *The members of the International Council of Emboli Management (ICEM) Study Group are listed in the Appendix. Address reprint requests to Dr Harringer, Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Carl-Neuberg-Str 1, Hannover, Germany; harringer@thg.mh-hannover.de In recent years neurologic injury during cardiac operation has received increased attention from cardiac surgeons. Although the causes of neurologic injury during cardiac operation are clearly multifactorial, age and atherosclerosis of the ascending aorta have been identified as major risk factors [1, 2]. In 1996, Roach and colleagues [3] published the results of a landmark study enrolling 2,417 patients who underwent elective coronary artery bypass grafting (CABG) to assess the incidence of adverse perioperative cerebral outcomes. Perioperative adverse cerebral outcomes affected 6.1% of the patients with 3.1% classified as type I injury (death due to stroke or hypoxic encephalopathy, nonfatal stroke, transient ischemic attack, stupor, or coma at the time of discharge) and 3.0% classified as type II injury (new deterioration in intellectual function, confusion, agitation, disorientation, memory deficit, or seizure without evidence of focal injury). Patients with adverse cerebral outcomes had 5 to 10 times the mortality, 2 to 4 times the time spent in intensive care, and 3 to 6 times the need for prolonged care when compared with patients without neurologic injury. In addition, it was clearly demonstrated that the single most important risk factor for adverse neurologic events was the presence of proximal aortic atherosclerosis as determined by surgical palpation. In a subsequent study of 273 patients who underwent intracardiac and coronary artery surgical procedures, it was further demonstrated that significant risk factors for type I outcomes are related primarily to embolic phenomena, including proximal aortic atherosclerosis, intracardiac thrombus, and intermittent clamping of the aorta during operation [4]. Additionally, Barbut and coworkers [5 7] were able to demonstrate a strong correlation between the severity of aortic atheroma and amount of emboli released, utilizing transcranial Doppler (TCD) and transesophageal echo (TEE). They were also able to demonstrate that most emboli (60%) are released during clamp manipulation of the ascending aorta, primarily following cross-clamp removal [5 7]. It was thus hypothesized that the use of an intraaortic filter during cardiac operation should reduce neurologic injury. To answer this question, the International Council of Emboli Management (ICEM) (see Appendix) established a prospective, consecutive enrollment, multiinstitutional 2000 by The Society of Thoracic Surgeons /00/$20.00 Published by Elsevier Science Inc PII S (00)

2 1120 MINIMALLY INVASIVE HARRINGER Ann Thorac Surg EMBOLI FILTRATION IN CARDIAC SURGERY 2000;70: Table 1. Patient Demographics Variable Mean Range Female/Male 31%/69% Age (years) NYHA classification LVEF (%) Aortic outer diameter (mm) N 304. LVEF left ventricular ejection fraction; Association. NYHA New York Heart Fig 1. EMBOL-X Intraaortic Filtration System (EMBOL-X Inc, Mountain View, CA) showing filter cartridge inserted in cannula and filter mesh deployed. registry of patients in whom intraaortic filtration has been used during cardiopulmonary bypass (CPB). Material and Methods Patients undergoing CPB for cardiac surgical procedures by median sternotomy were prospectively and consecutively enrolled in the ICEM Registry. Patient selection was at the discretion of the surgeon. Only patients with aortic aneurysm and congenital anomalies of the aortic arch were excluded. After routine anesthesia induction, the aorta was evaluated by palpation, TEE, or epiaortic scanning to assess the size, presence, and severity of aortic atherosclerosis. Forty-six percent of the aortas were evaluated using TEE or epiaortic scanning. An appropriately sized intraaortic filter (EMBOL-X, Inc, Mountain View, CA) was selected based on these findings. The intraaortic filtration system consists of a cartridge containing a heparin-coated 120-micron polyester Fig 2. Particulate found in filter mesh, gross visual examination at 10 magnification. (A) Particulate from 66-year-old male presenting with NYHA class 3 4. Procedure was a CABG 3. Time on CPB 85 minutes, cross-clamp time 55 minutes, filter dwell time 57 minutes. Histologic finding showed capture of fibrous atheroma. Patient recovered uneventfully. (B) Particulate from a 65-year-old male of NYHA class 2. Procedure was a CABG 3. Time on CPB 95 minutes, cross-clamp time 72 minutes, filter dwell time 25 minutes. Histologic findings included fibrous atheroma and thrombus/rbc. Patient recovered uneventfully. (C) Particulate from a 69-year-old male of NYHA class 3. Procedure was a CABG/valve combination. Time on CPB 171 minutes, cross-clamp time 106 minutes, filter dwell time 45 minutes. Histologic findings indicated material was of fibrous atheromatous origin. Patient recovered uneventfully.

3 Ann Thorac Surg MINIMALLY INVASIVE HARRINGER 2000;70: EMBOLI FILTRATION IN CARDIAC SURGERY 1121 Table 2. Histopathologic Results Result % Fibrous atheroma/cap 62% Fibrocalcific atheroma 5% Grumous atheroma/cholesterol 2% Medial tissue 4% Epiaortic debris (suture, hyaline cartilage, fat) 6% Platelets/fibrin 52% Thrombus/RBC 22% N 243. No particulates were seen in 3 filters. RBC red blood cells. mesh net that deploys with a syringe-like motion. The net is inserted into the aorta through a 24F arterial return cannula with an effective flow rate equivalent to a standard 20F arterial cannula. The cannula is modified with a side port to accommodate the interlocking filter cartridge (Fig 1). Routine cannulation procedures for CPB were performed with the arterial cannula inserted in the ascending aorta and secured using double purse-string sutures. The intraaortic filter was deployed prior to removing the aortic cross-clamp and remained in place during positioning and removal of the partial occlusion clamp. The filter was removed through the side port prior to decannulation. Cross-clamp time, CPB time, type of procedure, CPB flow rates, filter dwell times, and partial aortic cross-clamp use were recorded. Clinical assessment included basic neurologic examinations preoperatively, first day postoperatively, and before discharge. Upon removal, filters were visually inspected for captured material, collected in specimen tubes, fixed in formalin, and shipped to a central pathology laboratory (Stanford University, Stanford, CA) for further analysis. Filter analysis included gross visual examination (10 magnification) to determine the quantity and size of the particulate captured, as well as histologic examination (stains with hematoxylin and eosin, trichrome, and Elastica van Gieson) for the presence of platelets and fibrin deposition, true thrombus or blood clot, grumous portion of atheroma/cholesterol, fibrous atheroma or fibrous cap, medial tissue, and epiaortic debris. Results As of January 2000, 304 patients have been enrolled in the registry. Neurologic and clinical outcome data forms are completed for 280 patients, which thus constitute the current study cohort. Patient demographics represent the usual distribution of age, sex, and comorbidities (Table 1). Operative procedures included CABG (59%), valve repair/replacement (20%), combination CABG and valve replacement (12%), and other cardiac procedures (9%). Patients entered into the registry were generally higher risk candidates for cardiac procedures. Risk factors included congestive heart failure (19%), aortic atherosclerosis (17%), history of neurologic events (11%), and carotid stenosis greater than 50% (10%). Eighty percent had two or more comorbidities and 43% had four or more. Average filter deployment duration was 33 minutes (range 2 to 95 minutes). Cardiopulmonary bypass times (mean 106 minutes; range 37 to 390 minutes) and cross-clamp time (mean 65 minutes; range 21 to 205 minutes) were within normal ranges. Partial clamps were used in 84% of the CABG procedures. Filter deployment was simple and successful in all patients. There were no filter-related adverse events nor were there any incidences of aortic dissection. Consistent with the risk profile of the study population, there were 16 (5.7%) deaths. Short transient delirium ranging from 24 to 48 hours was reported immediately postoperatively in 9 patients (3.2%). The registry showed 1 patient with a transient ischemic attack (0.36%), 2 patients with stroke (0.71%), and 1 patient with a coma (0.36%). Hard granular particulate or soft material was seen upon visual examination in 240 of the 243 filters (99%) (Fig 2). Mean number of particles per filter was 8.2 (range 0 to 35) and mean surface area of particles per filter was 7.7 mm 2 (range 0 to 67 mm 2 ). Histologic examination differentiated the captured particulate into presence or absence of platelet/fibrin deposition, true red blood cell thrombus (blood clot), grumous atheroma, fibrous atheroma or fibrous cap (with or without calcification or grumous/cholesterol), and medial tissue. Fibroatheromatous material, including needle-shaped cholesterol fragments and atheroma, was the type of particulate most often found in the 243 filters examined. Fibrous atheroma or fibrous cap was present in 62% (151 of 243) of the filters. Fibrin, with and without the obvious presence of platelets, was present in 52% (127 of 243) of the filters, and true thrombus (including clot rich with erythrocytes) was present in 22% (54 of 243) of the filters. Medial tissue was present in 4% of the filters and grumous portion of the atheromatous plaque was found in 2% (4 of 243) of the filters. Mature hyaline cartilage, suture material, and fat was also found (Table 2). Comment In recent years, there has been an increasing awareness of atheromatous disease within the aorta and its role as a source of emboli during cardiac operation. Recent studies have demonstrated a correlation between the degree of embolic material and neurologic damage [5, 8]. The relationship between the rising age of patients and the increase in central nervous system complications associated with cardiac operation has become evident in these and other studies [1]. Embolization has been shown to start at the beginning of CPB and it is dramatically increased when the aortic cross-clamp is removed [5 7]. Emboli appearing at the inception of bypass are most likely gaseous, while those appearing upon the release of the aortic clamps are suspected to largely contain particulate debris from atheromatous plaques in the ascending aorta. Although previous studies have clearly documented the existence and impact of embolic release during cardiac operation, all of these studies have been limited by

4 1122 MINIMALLY INVASIVE HARRINGER Ann Thorac Surg EMBOLI FILTRATION IN CARDIAC SURGERY 2000;70: the fact that embolic activity is measured indirectly through TEE or TCD. Clinical events caused by emboli are difficult to prove without autopsy analysis. Further, neither TEE nor TCD have been able to reliably distinguish between particulate and gaseous material. The data from the ICEM Registry provide direct evidence that atheromatous material released from the aorta during surgical procedures is present in most cardiac procedures and that this material can be effectively removed before entering into distal circulation. Using TEE and TCD to determine emboli size, Barbut and colleagues [6] reported that 72% of emboli measured more than 600 m in diameter (28% more than 1,000 m and 44% between 600 and 1,000 m), and 27% measured 600 m or less in diameter. The 120- m mesh of the filter is sized significantly smaller than most emboli released. Although the ICEM data clearly demonstrate the efficacy of intraaortic filtration in capturing and removing particulate debris, the clinical impact of particulate removal remains a crucial question. Patients enrolled in the ICEM Registry had at least equivalent if not higher risk profiles than those studied in the Roach and colleagues prospective observational study [3]. Presence of aortic atheromatosis (Roach 12.4%; ICEM 16.6%), history of neurologic events (Roach 8.3%; ICEM 10.7%), age greater than 70 years (Roach 31.9%; ICEM 53.9%), hypertension (Roach 57.2%; ICEM 62.68%), and diabetes (Roach 25.1%; ICEM 18.3%) have all been identified as predictors of adverse neurologic events. In addition, whereas the Roach study was limited to CABG patients only, the ICEM group includes all procedures in which an aortic cross-clamp is used, such as valve, combination CABG/ valve, and other procedures. Although the ICEM Registry population included patients at higher risk, the incidence of stroke in the ICEM group (0.7%) was surprisingly low. In the ICEM Registry, all type I outcomes were significantly lower (1.4%) than those reported in the Roach study (3.1%) [3]. Of the 2 patients who had a stroke in the ICEM Registry group, the first patient died on postoperative day 2 after remaining in a coma following a combined aortic valve replacement and carotid endarterectomy. In the second case, the patient presented with chronic atrial fibrillation, initially recovered normally, and on postoperative day 3 had a stroke. The patient who was in a coma was an urgent case presenting with multiple comorbidities, including preexisting stroke, delirium, memory deficit, peripheral neuropathy, cardiogenic shock, and diabetes and died on postoperative day 24 without regaining consciousness. In all of these cases, it is doubtful that the event experienced was related to particulate matter released perioperatively from the ascending aorta. Despite a reduction in focal neurologic injury in the ICEM Registry population, the benefit in improving type II outcomes (Roach 3.0%; ICEM 3.2%) was not evident. One could speculate that the pathogenesis of type II injuries after cardiac operation might be different from focal damages. Hypoperfusion, inflammatory response due to CPB, and anesthetic agents could play a greater role in patients with cognitive dysfunction. Because the ICEM registry was not designed to test a specific hypothesis and does not encompass a control group, our ability to draw conclusions from these data is limited. Patient enrollment in this registry is still preliminary, and larger numbers will be needed to clarify conclusions from these data. In addition, a multicenter study on selected patients with a blinded neurologic analysis will be needed to confirm the significance of these trends. Nevertheless, these data begin to validate the theory posted in previous studies that particulate matter released intraoperatively is a causative factor in permanent focal neurologic injury. Despite the current increase in off-pump coronary bypass operations, data emerging on neurologic outcomes have failed to demonstrate an improvement. This finding might reflect emboli release during partial aortic clamping, which was applied in most off-pump patients [9]. The ICEM data demonstrate the safety and clear efficacy of intraaortic filtration in capturing and removing particulate debris. In addition, the low rates of adverse type I outcomes may show a trend toward reduction of permanent focal neurologic injury related to removal of atheromatous emboli. Due to the structure of patient enrollment and data collection in a prospective registry, the clinical significance of intraaortic filtration should be evaluated further in a randomized prospective multicenter study. In the meantime, in patients at risk for adverse neurologic events and in whom the ascending aorta is manipulated during cardiac operations, intraaortic filtration is advisable. References 1. Blauth CJ, Cosgrove DM, Web BW, et al. Atheroembolism from the ascending aorta: an emerging problem in cardiac surgery. J Thorac Cardiovasc Surg 1992;103: Davila-Roman VG, Barzilai B, Wareing TH, Murphy SF, Schechtman KB, Kouchoukos NT. Atherosclerosis of the ascending aorta: prevalence and role as an independent predictor of cerebrovascular events in cardiac patients. Stroke 1994; 25: Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996;335: Wolman RL, Nussmeier NA, Aggarwal A, et al. Cerebral injury after cardiac surgery. Identification of a group at extraordinary risk. Stroke 1999;30: Barbut D, Hinton RB, Szatrowski TP, et al. Cerebral emboli detected during bypass surgery are associated with clamp removal. Stroke 1994;25: Barbut D, Yao F-S, Lo Y-W, et al. Determination of size of aortic emboli and embolic load during coronary artery bypass grafting. Ann Thorac Surg 1997;63: Barbut D, Yao FS, Hager DN, Kavanaugh P, Trifiletti RR, Gold JP. Comparison of transcranial Doppler ultrasonography and transesophageal echocardiography to monitor emboli during coronary artery bypass surgery. Stroke 1996;27: Barbut D, Lo Y-W, Gold JP, et al. Impact of embolization during coronary artery bypass grafting on outcome and length of stay. Ann Thorac Surg 1997;63: Arom KV, Flavin TF, Emery RW, Kshettry VR, Janey PA, Petersen RJ. Safety and efficacy of off-pump coronary artery bypass grafting. Ann Thorac Surg 2000;69:

5 Ann Thorac Surg MINIMALLY INVASIVE HARRINGER 2000;70: EMBOLI FILTRATION IN CARDIAC SURGERY 1123 Appendix Members of the International Council of Emboli Management (ICEM) Study Group Name Institution City Country Torkel H.J. Åberg, MD University Hospital of Northern Sweden Umeåa Sweden Johannes O. Bonatti, MD University of Innsbruck Innsbruck Austria Michael Grimm, MD, PhD University of Vienna Vienna Austria Wolfgang Harringer, MD, PhD Hannover Medical School Hannover Germany Joao Q. Melo, MD, PhD Santa Cruz Hospital Lisbon Portugal Hermann Reichenspurner, MD, PhD University Groshadern Munich Germany Patrick Ruchat, MD Centre Hospitalier Universitaire Vaudois (CHUV) Lausanne Switzerland Christoph Schmitz, MD University of Bonn Bonn Germany Marko I. Turina University Hospital Zurich Switzerland Jarle Vaage, MD, PhD Karolinska Institute Stockholm Sweden Wim-Jan P. van Boven, MD St. Antoninus Zieckenhuis Nieuwegein The Netherlands Gerhard Wimmer-Greinecker, MD, PhD J.W. Goethe University of Frankfurt Frankfurt Germany