Aortic valve replacement has become a straightforward operation, accompanied by low mortality rates. In the elderly and childbearing populations, the use of bioprosthetic valves has supplanted that of mechanical prostheses. We present the case of a patient with a newly implanted bovine heterograft in which hyperacute fibrin deposition developed, resulting in outflow obstruction and cardiac decompensation.
Case Report
In September 2003, a 75-year-old white Jewish man with a history of seizure disorder, transient ischemic attacks, rheumatic fever, and polycythemia vera presented with increasing fatigue and exercise intolerance. He underwent cardiac catheterization and echocardiography in order to evaluate a murmur that was consistent with aortic stenosis. These studies demonstrated severe aortic stenosis (valve gradient, 60 mmHg; valve area, 0.6 cm2), normal left ventricular function, mild biatrial enlargement, and normal coronary arteries. The preoperative hematocrit was 51.3%, the platelet count 430,000/mm3, and the international normalized ratio (INR) 1.3. The patient had no history of vascular thrombosis or of heparin exposure.
The patient underwent aortic valve replacement using a bioprosthetic valve. At the time of operation, the cause of the aortic stenosis was determined to be senile calcification. The valve was replaced with a standard 23-mm Carpentier-Edwards PERIMOUNT® pericardial aortic prosthesis (Edwards Lifesciences; Irvine, Calif). The operative course was unremarkable: the patient was cooled to 34 °C, hypo-retrograde, the aorta was cross-clamped for 40 minutes, and intraoperative transesophageal echocardiography demonstrated accurate seating of the prosthesis and leaflet function. The patient required no inotropic support perioperatively. His initial postoperative cardiac output was 5.7 L/min, and the first 16 hours of his postoperative course were unremarkable.
The next morning, the patient's respiratory and clinical status acutely deteriorated, clinically consistent with cardiogenic shock. His troponin level was 2.3 ng/mL; hematocrit, 37.5%; platelet count, 392,000/mm3; and INR, 1.6; and an electrocardiogram showed an inferior lateral wall myocardial infarction. Refractory hypotension required intravenous dobutamine and dopamine. The patient's heart further decompensated and became asystolic 20 hours after the initial procedure. The chest was opened at bedside, and it was noted that there was minimal spontaneous cardiac activity. Despite manual cardiac massage and the administration of intracardiac pressors, the patient died. Postmortem examination revealed severe fibrin and leukocyte aggregation on the implanted aortic heterograft (Fig. 1), left ventricular hypertrophy, and no sign of acute coronary thrombosis.
Fig. 1 Severe fibrin and leukocyte aggregates on the ventricular side of all 3 leaflets of the aortic valve bioprosthesis.
Discussion
The diseased aortic valve can be replaced with a bioprosthetic or mechanical valve. Factors favoring a bioprosthesis include intolerance to anticoagulation, pregnancy, limited life expectancy, and a history of thrombosed mechanical valve. The disadvantage of the bioprosthetic valve is structural deterioration that occurs after an average of 13 years. Glutaraldehyde tanning prolongs the structural integrity of bioprosthetic valves and has replaced formaldehyde in that application, because glutaraldehyde irreversibly crosslinks the graft proteins, rendering them nonimmunogenic. However, this process has not proved to prevent cell-mediated or antibody-mediated immunologic responses in vitro or in vivo.
Bioprosthetic rejection theoretically occurs via 2 different pathways. A cellular immune response may develop over weeks or months, is mediated by T cells, and is confirmed pathologically by finding host cells acutely involved in the rejection process. The 2nd form of rejection is antibody-mediated host recognition of a foreign body, such as a glutaraldehyde-treated xenograft. Pathologically, the foreign body becomes coated with an acellular matrix composed of fibrin, without evidence of host reaction or infiltration of T cells. Thrombosis of a bioprosthetic valve may be initiated and accompanied by either form of rejection.1
Hyperacute rejection is due to presensitization of the recipient to a donor antigen and develops in the 1st minutes or hours after implantation. Our patient had no known previous exposure to glutaraldehyde, and the bioprosthesis was confirmed to be bovine. Because of the timing of the rejection and the acellular pathology, we believe that the mechanism of the accelerated valve dysfunction most likely was antibody-related foreign-body rejection. Unfortunately, due to the rapid clinical decompensation in hyperacute rejection, radiation and rescue agents that are used routinely to treat rejection have no defined role. On transesophageal echocardiogram and at autopsy, we detected no valve cusp fusion or calcification, which is occasionally described in early bioprosthetic graft failures.2
We questioned whether the patient's polycythemia could be responsible for the fibrin and leukocyte aggregation on the implanted valve. Several factors argue against this hypothesis: the patient had no known prior thrombotic events, his hematocrit and platelet count were not elevated preoperatively (the 2 factors most predictive of thrombotic events), the event occurred in the arterial system (venous is more frequent), there was no evidence of a low cardiac output state postoperatively, and there was no evidence of thrombus elsewhere. In addition, the absence of red blood cells in the pathologic specimen argues against primary thrombus formation. Due to the rapidity of the patient's decompensation, we were unable to check for heparin antibodies or for a hypercoagulable state, although neither would have explained why the disease was limited to the aortic valve bioprosthesis.
To our knowledge, this is the only reported case of hyperacute rejection of a bovine pericardial prosthesis. We have been unable to identify any predisposing risk factors in the patient, despite an extensive literature search in which we found discussions of polycythemia vera and hematological disorders.
Footnotes
Address for reprints: Frankie A. Puckett, MD, Department of Surgery, Mercy Hospital of Pittsburgh, 1400 Locust Street, Pittsburgh, PA 15219. E-mail: Puckett_frankie@yahoo.com
References
- 1.Dahm M, Lyman WD, Schwell AB, Factor SM, Frater RW. Immunogenicity of glutaraldehyde-tanned bovine pericardium. J Thorac Cardiovasc Surg 1990;99:1082–90. [PubMed]
- 2.Talbert WM, Wright P. Acute aortic stenosis of a porcine valve heterograft apparently caused by graft rejection: case report with discussion of immune mediated host response [published erratum appears in Tex Heart Inst J 1982;9:372]. Tex Heart Inst J 1982;9:225–9. [PMC free article] [PubMed]