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Ann Thorac Surg 2003;76:1114-1118
© 2003 The Society of Thoracic Surgeons


Original article: cardiovascular

Cardiac surgery in patients infected with the human immunodeficiency virus

Gregory D. Trachiotis, MDa, E. Pendleton Alexander, MDa*, Debra Benator, MDa, Farid Gharagozloo, MDa

a Divisions of Cardiothoracic Surgery and Infectious Disease, VAMC, Washington, DC, USA, and George Washington University Medical Center, Washington, DC, USA

* Address reprint requests to Dr Alexander, Cardiothoracic Surgery, 2150 Pennsylvania Ave, Suite 6B, Washington, DC 20037, USA.
e-mail: ealexander{at}mfa.gwu.edu

Presented at the Forty-eighth Annual Meeting of the Southern Thoracic Surgical Association, San Antonio, TX, Nov 8–10, 2001.


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Discussion
 References
 
BACKGROUND: Highly active antiretroviral therapy has dramatically impacted the natural history of human immunodeficiency virus (HIV) infection and may be associated with lipodystrophy and accelerated coronary artery disease. Patients with HIV are consequently increasingly likely to present for cardiac surgery.

METHODS: A retrospective review of 37 consecutive patients at two integrated centers from 1994 to 2000 was conducted. Standard database and follow-up information was supplemented with data on opportunistic infections, CD4 count, viral load, New York Heart Association status, and angina status. Risk to operating room personnel was also reviewed.

RESULTS: Median age was 41 years; 34 of 37 patients were male. Operations performed were coronary artery bypass graft ([CABG] 27), aortic valve replacement ([AVR] 4), AVR/CABG (2), AVR/mitral valve repair (1), mitral valve repair (1), excision of atrial masses (1), and tricuspid valve repair (1). Complications included death in 1 of 37 (2.7%), sepsis in 2 of 37 (5.4%), deep sternal infection in 1 of 37 (2.7%), bleeding in 2 of 37 (5.4%), prolonged ventilation in 2 of 37 (5.4%), and readmission in 8 of 37 (21.6%). Actuarial freedom from a composite end point of angina, death, myocardial infarction, repeat revascularization, and congestive heart failure was 81% at 3 years with no late deaths. Preoperative and follow-up CD4 counts and viral loads were not significantly different at a mean follow-up of 28 months. No patients progressed from HIV positive status to AIDS during the study period. Six "needle stick" injuries requiring antiretroviral prophylaxis occurred in 5 caregivers without seroconversion.

CONCLUSIONS: In selected patients infected with HIV, risks and outcomes of cardiac surgery are acceptable. With concomitant highly active antiretroviral therapy, intermediate HIV and cardiac status appear to be favorable. Needle stick injuries occur at a rate mandating optimal reduction of patient viral loads preoperatively.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Discussion
 References
 
Few areas of medicine have seen such dramatic changes in treatment and resulting reduction in morbidity and mortality as the management of human immunodeficiency virus (HIV) infection. The introduction of highly active antiretroviral therapy (HAART) in general and protease inhibitors (PI) in specific during the mid 1990s allows for sustained inhibition of viral replication and partial immune reconstitution in most patients [13]. As HIV has changed from a progressive, morbid, frequently fatal illness to a chronic condition, many infected patients increasingly require diverse health services including cardiac surgery [4]. Previously described cardiac manifestations of HIV disease include pericardial disease, myocarditis, and endocarditis [510].

With decreasing death and conversion of HIV infection to the acquired immune deficiency syndrome (AIDS), indications other than endocarditis are likely to bring these patients to the attention of cardiac surgeons. Some features of the treatment of HIV disease may also contribute to the development of cardiac disease. There is increasing evidence for the development of premature coronary artery disease in this population [1016]. In addition to contributory factors such as endothelial dysfunction, hypercoagulability, hyperlipidemia, and distinct coronary artery pathology, there is now evidence for accelerated altherosclerosis from protease inhibitors. These drugs, largely responsible for the dramatic change in the natural history of HIV disease, are associated with insulin resistance, hypercholesteroemia, and a lipodystrophy fat redistribution syndrome [1113].

Decisions regarding the appropriateness of cardiac surgery in this patient group require the analysis of the prognosis of two distinct diseases. This study was undertaken to address the following issues: (1) Are HIV cardiac surgery patients at increased or inordinate risk from complications related to a deficient immune system? (2) Does cardiac surgery potentially accelerate the natural history of HIV disease? (3) Does the prognosis of HIV disease limit the potential benefit of successful surgery? (4) What is the risk to the operative team?


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Discussion
 References
 
Patients
A retrospective review was conducted of 37 consecutive patients with documented positive HIV serology undergoing cardiac surgical operations at two integrated centers from January 1994 to December 2000. Preoperative, operative, postoperative, and follow-up data using hospital and clinic records and interviews were utilized. Of the 37 patients, 27 underwent isolated coronary artery bypass grafting (CABG) and 10 underwent valvular procedures. The latter included aortic valve replacement (AVR) in 4, AVR/CABG in 2, AVR/mitral valve repair in 1, excision of atrial and tricuspid masses in 1, and tricuspid valve repair in 1. Data compiled included cardiac events, angina, and New York Heart Association (NYHA) status and details of each patient’s HIV disease including intervening course, CD4 count, and HIV viral loads.

No specific criteria were used to select patients for operation although patients were selected for operation when their HIV disease showed evidence of a stable course and there were compelling cardiac symptoms or disease carrying the risk of premature death. Over the study period increasing numbers of patients were accepted for myocardial revascularization and other conventional indications for cardiac surgery other than bacterial endocarditis. A stable HIV course typically included the absence of concurrent opportunistic infections, adherence to an antiretroviral regimen, CD4 count greater than 300, and HIV viral load less than 10,000 copies/mL. Preoperative characteristics of the 37 patients are listed in Table 1. Overall, both the CABG and valve cohorts consist of predominately young male patients. Significant differences between these two subgroups are limited to age and preoperative HIV viral load. These differences likely exist because of the preponderance of very young intravenous drug abusers in the valvular group. There is a striking incidence of hepatitis C and B coinfection and tobacco abuse in the entire study group.


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Table 1. Preoperative Clinical Data

 
At operation all CABG patients received a left internal mammary artery graft. Three of the 27 isolated CABG procedures were performed off cardiopulmonary bypass. Indications for surgery in the CABG group were typically compelling: unstable angina with high-risk anatomy in 12 of 27 (44%), left main coronary artery disease in 9 of 27 (33%), and postinfarction angina with high-risk anatomy in 6 of 27 (22%).

Valvular operations were done for endocarditis and its sequelae in 6 of 10 patients. Perivalvular abscesses were present in 4 of these patients. Causative organisms included Staphylococcus aureus in 2 patients, Staphylococcus epidermidis in 1 patient, Enterocccus species in 1 patient, and Candida species in 2 patients. Concomitant CABG was performed in 2 of the 10 valvular procedures.

Cholesterol data were compiled with a particular interest in the impact of protease inhibitors on this variable. In addition to HIV-related illness, postoperative CD4 and HIV viral load were recorded when obtained within 6 weeks postoperatively to evaluate the impact of cardiac surgery on these markers of HIV disease.

Endpoints in the outcome analysis included death, occurrence of class III or higher angina or heart failure, and repeat revascularization.

Statistical methods
The {chi}2 and Fisher’s exact tests were used to test whether relationships existed between nominal variables. Outcome analysis was conducted from the date of operation to the date of death, symptom development, or repeat revascularization with follow-up to August 1, 2001. Actuarial freedom from these events was calculated using the Kaplan-Meier method and comparison made using the log rank test.


    Results
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 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Discussion
 References
 
Perioperative course
Perioperative data are summarized in Table 2. Mean grafts per patient in the CABG group was 2.3, suggesting a more targeted approach to revascularization. Mortality was observed in a single patient after aortic valve replacement who became septic on the day of discharge and succumbed 24 hours later. Twenty-two complications were observed in 14 patients, predominately infectious in nature. There were no instances of stroke, renal failure, or perioperative myocardial infarction.


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Table 2. Perioperative Clinical Data

 
Hiv disease outcome
At a mean follow-up of 2.4 years no patient had developed an opportunistic infection. A single patient was diagnosed with HIV dementia not thought to be present before surgery, the only patient to develop an AIDS-defining condition during the follow-up period.

CD4 and HIV viral loads preoperatively and postoperatively were available for comparison in 31 of 36 survivors. The mean preoperative CD4 of 360 (range 106 to 560) was not significantly different from the postoperative CD4 of 353.8 (range 174 to 570). Mean preoperative HIV viral load of 11,085 copies/mL (range < 50 to 156,000) was not significantly different from mean postoperative HIV viral loads of 3,482 copies/mL (range < 50 to 23,000).

Impact of protease inhibitors
Twenty-three of the 29 patients receiving bypass grafts were on protease inhibitors preoperatively. None of these patients had symptomatic coronary artery disease documented at the time of protease inhibitor initiation. Cholesterol measurements before and after protease inhibitor initiation were available for 23 of 37 total study patients. Increases of more than 25 mg/dL were seen in 19 of 23 patients. Preprotease inhibitor cholesterol levels (mean 166.8, range 119 to 244) differed significantly from post–protease inhibitor cholesterol levels (mean 218.1, range 146 to 301; p < 0.0001).

Cardiac outcome
Actuarial freedom from class III angina or failure symptoms, myocardial infarction, death, and repeat revascularization is depicted in Figure 1 for the CABG group, the valve group, and the group as a whole. At 3 years, freedom from this composite end point was 81% for the group as a whole.



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Fig 1. Actuarial freedom from a composite end point of death, class III or IV angina or congestive heart failure, revascularization. There is no significant difference for the coronary artery bypass graft subgroup (solid line) versus the valve subgroup (dashed line). Dotted line = total.

 
Operative team risk
Six "needle stick" injuries requiring antiretroviral prophylaxis occurred in 5 surgical team members over the course of the study. These injuries involved an attending surgeon (3), an anesthesia resident (1), a scrub nurse (1), and a first assisting physician assistant. All took prophylactic antiretroviral therapy. No HIV seroconversion was noted.

Side effects from the prophylactic regimen (nausea, headache, abdominal distention) were common. No data were available on the possibility of hepatitis B or C transmission.


    Comment
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Discussion
 References
 
Patients with HIV infection will present for cardiac surgery with increasing frequency as a consequence of the signal change in the outcome of HIV disease that began in the mid 1990s. Bacterial endocarditis, the predominant indication for surgery in the earlier years of the "AIDS epidemic" [7], will remain a surgical indication but will be supplemented by a large number of patients requiring myocardial revascularization and other cardiac operations. This will occur not only because of the new chronicity of HIV infection in most patients but also from specific aspects of the disease and its treatment.

Protease inhibitors have significantly changed the outlook of HIV infection. The impact on cholesterol levels and the temporal relationship of protease inhibitors with presentation of coronary artery disease seen in this study have been previously reported [8, 1116]. The impact of protease inhibitors on cholesterol and lipid metabolism can potentially alter the mid- or long-term results of revascularization. The postoperative treatment regimen in these patients should include aggressive anticholesterol therapy. Pravastatin is recommended over other similar cholesterol-lowering "statin" drugs because of more predictable pharmacokinetics with concomitant HAART [11].

Reports of CABG in HIV infected patients have been limited to date [1719] but the results are generally favorable. In this study mortality and morbidity are acceptable although the incidence of infectious complications may be higher than it is for non-HIV patients with otherwise similar surgical risk. Functional results appear to be good in both the CABG and valve subgroups at a mean follow-up of 2.4 years. It should be noted that case selection in this series was cautious, both in terms of the stability of the HIV disease and the operability of the cardiac disease

Fears about the progression of HIV disease as a consequence of cardiac surgery in general and cardiopulmonary bypass in particular appear to be unfounded, especially in the current era of HAART. As surrogates for the progression of HIV disease, the absence of new opportunistic infections and the lack of deterioration in CD4 counts or viral load are reassuring.

The incidence of needle stick injury is concerning. Perhaps more concerning is the high coinfection rate with hepatitis C seen in this cohort of patients, for which no effective prophylactic regimen currently exists [20]. Guidelines for health care workers in general [20] and cardiac surgical teams in specific [17] have been well described. In addition to these measures, limiting the operative team to experienced, seasoned care givers and maximal reduction of HIV viral loads with aggressive HAART before surgery appear warranted.


This article has been selected for the open discussion forum on the CTSNet Web site: http://www.ctsnet.org/discuss

 


    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Discussion
 References
 
DR THORALF SUNDT (Rochester, MN): Did you have any particular policies with respect to the coronary patients? Were they done on pump or off pump, and which do you think actually poses less of a risk to healthcare personnel? Are you concerned about aerosolizing blood with the CO2 blowers?

DR TRACHIOTIS: A very good point, Dr Sundt. I think I would like to emphasize that to do these types of risk patients I think we would all like to be in a comfortable operating room environment. Our team has been together for more than 8 years. To directly answer your question, 3 of the patients had off-pump surgery, and those were for isolated vessels or target revascularization. I think the technical point, in terms of limiting spread in blood products, is certainly an important concern and to have a more controlled environment actually may be desirable. I believe the study also demonstrates, as have other reports in the literature, that actually placing patients on bypass does not augment their disease progression.

DR WILLIAM BAUMGARTNER (Baltimore, MD): Greg, that was really a nice presentation. These protease inhibitors have turned this acute disease into an absolute chronic disease and in addition has resulted, as you pointed out, in an increase in coronary artery disease in this patient population. You have also provided important observations to all of us that we will likely see an increased number of HIV-positive patients.

You told us about your selection criteria but would you tell us which HIV patients you would not consider for operation? We all practice universal precautions in the operating room. Do you do anything different for this particular group of patients whom you know have HIV-positive disease?

DR TRACHIOTIS: Thank you very much, Dr Baumgartner. I will take the second question first. There are some maneuvers that we do perform. Our team members have been together for 8 years and for these types of patients we do up front let the team know the potential risk and have only really the experienced team members participate. We give the cardiac trainees and PAs the options of not scrubbing, and therefore sometimes it is a two-attending case. The instruments are not passed had to hand but are laid down so that the surgeons actually will pick them up, so that the needle-stick potential is reduced. Usually the first assistants are very experienced, so that they can anticipate the maneuvers of the operating surgeon. But, as demonstrated, I think you see that needle-stick injuries still occur, unfortunately.

With regard to patient selection, I think we do have a fairly rigid policy. I think patients in general who aren’t compliant with their therapy—because it is tremendously beneficial at reducing their viral loads and giving them immunocompetence—or who have had a recent opportunistic infection, or who have other comorbid conditions that would actually limit their long-term survival, I think those patients we would probably choose not to operate on.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Discussion
 References
 

  1. Karon J.M., Flemming P.L., Stecker R.W., De Lock K.M. HIV in the United States at the turn of the century: an epidemic in transition. Am J Public Health 2001;91:1060-1068.[Abstract]
  2. Palella F.J., Delaney K.M., Moorman A.C., et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998;338:853-860.[Abstract/Free Full Text]
  3. Lederman M.M., Valdez H. Immune restoration with anti-retroviral therapies. Implications for clinical management. JAMA 2000;284:223-228.[Abstract/Free Full Text]
  4. Hidalgo J.A., MacArthur R.D., Leone L.R. An overview of HIV infection and AIDS: etiology, pathogenesis, diagnosis, epidemiology, and occupational exposure. Semin Thorac Cardiovasc Surg 2000;12:130-139.[Medline]
  5. Cotton P. AIDS giving rise to cardiac problems. JAMA 1990;263:2149.[Medline]
  6. Yumis N.A., Stone V.E. Cardiac manifestation of AIDS: a review of disease spectrum and clinical management. J Acqui Immune Defic Syndr Hum Retroviral 1998;18:145-154.[Medline]
  7. Frater R.W., Sisto D., Condit D. Cardiac surgery in human immunodeficiency virus (HIV) carriers. Eur J Cardiothoracic Surg 1989;3:146-150.[Abstract]
  8. Rerkpattanapipat P., Wongprapurat N., Jacobs C.E., Kotler M.N. Cardiac manifestations of acquired immunodeficiency syndrome. Arch Intern Med 2000;160:602-608.[Abstract/Free Full Text]
  9. Malnick S., Goland S. Dilated cardiomyopathy in HIV infected patients. N Engl J Med 1999;4:732-733.
  10. Barbaro G. Cardiovascular manifestations of HIV infection. J R Soc Med 2001;94:384-390.[Free Full Text]
  11. Passalaris J.D., Sepkowitz K.A., Glesby M.J. Coronary artery disease and human immunodeficiency virus infection. Clin Infect Dis 2000;31:787-797.[Medline]
  12. Henry K., Mehoe H., Huebsch J., et al. Severe premature coronary artery disease with protease inhibitors. Lancet 1998;351:1328.[Medline]
  13. Sullivan A.K., Nelson M.R., Moyle G.J., et al. Coronary artery disease occurring with protease inhibitor therapy. Int J STD AIDS 1998;9:711-712.[Abstract/Free Full Text]
  14. Hayes P., Muller D., Kuchar D. Left main coronary artery disease in a 40 year old man receiving HIV protease inhibitors. Aust NZ J Med 2000;30:92-93.[Medline]
  15. Monsuez J.J., Gallet B., Escant L., et al. Clinical outcome after coronary events in patients treated with HIV-protease inhibitors. Eur Heart J 2000;21:2079-2080.[Free Full Text]
  16. Friedl A.C., Jost C.H., Schalcher L., et al. Acceleration of confirmed coronary artery disease among HIV infected patients on potent anti-retroviral therapy. AIDS 2000;14:2790-2792.[Medline]
  17. Frater R.W.M. Cardiac surgery and the human immunodeficiency virus. Semin Thorac Cardiovasc Surg 2000;122:145-147.
  18. Imanaka K, Takomoto S, Kimuric S, et al. Coronary artery bypass grafting in a patient with human immunodeficiency virus: role of peri-operative active anti-retroviral therapy. Jpn Circ J 199;63:423–4
  19. Flinn D.R., Tyras D.H., Wallack M.K. Coronary artery bypass grafting in patients with human immunodeficiency virus. J Card Surg 1997;12:98-101.[Medline]
  20. Centers for Disease Control and Prevention. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for post-exposure prophylaxis. MMWR 2001;50:1-52.[Medline]



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This Article
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Farid Gharagozloo
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