Mortality and Morbidity in HIV-Infected Patients Undergoing Coronary Artery Bypass Surgery: a Case Control Study

INTRODUCTION

The sustained inhibition of viral replication and immune reconstitution¹ associated with highly active antiretroviral therapy (HAART) has greatly improved prognosis in patients with human immunodeficiency virus (HIV). Increased survival and the metabolic side effects associated with antiretroviral therapy² have, however, led to increased cardiovascular risk^3-5 in these patients and an increased need for cardiac surgery.

Although good surgical outcomes have been obtained in HIV-infected patients, there is a lack of outcomes data from large series and case-control studies.^6-8 In the present study, we analyze our experience of performing isolated coronary artery surgery (CAS) in HIV-infected and non-HIV-infected individuals to determine whether HIV infection increases the risk of complications after cardiac surgery.

PATIENTS AND METHODS

Clinical records for patients who received an isolated CAS from June 1997 to January 2004 were reviewed retrospectively to identify all HIV-infected patients. No HIV-infected patient considered for surgery was rejected. As a control group, for each HIV-infected patient, 3 non-HIV-infected patients of the same age (±10 years) and sex were selected who had received the same type of intervention immediately prior to or after the corresponding HIV-infected patient. All patients received per-protocol antibiotic prophylaxis (intravenous glucopeptides/aminoglucosides).

Preoperative, perioperative, and postoperative data were obtained from clinical records. For HIV-infected patients, data on duration, stage (CDC classification⁹), CD4 T-lymphocyte cell count, and viral load were also collected. Patients' were classified for preoperative surgical risk using the EuroSCORE system.¹⁰

The mean overall and postoperative length of hospital stay was calculated, together with morbidity and mortality. Postoperative complications assessed included fever requiring treatment with antibiotics, sepsis, surface infection of the surgical wound, mediastinitis, anemia requiring transfusion, use of additional surgical procedures, urinary infection, pneumonia, catheter related bacteriemia, and stroke.

Follow-up data (status [alive/dead] and the need for a further CAS) were obtained via personal interview during periodic check-ups.

Statistical analyses were performed in SPSS (version 12.0, SPSS Inc., Chicago). Quantitative variables were expressed as means ± standard deviation and qualitative variables as percentages. Descriptive analysis was followed by between group comparisons using the χ² test or Fisher's exact test for qualitative variables, and non-parametric tests for numerical data. P values <.05 were considered statistically significant.

RESULTS

Characteristics of HIV-Infected Patients

Seven HIV-infected patients who received CAS were identified (0.5% of all CAS performed in the center during the study period). Risk factors for infection were injecting drug use in 1 (14.3%) patient, homosexual risk behaviors in 1 (14.3%), and heterosexual risk behaviors in 5 (71.4%). Mean time with the infection was 8.6 years (range, 2-15 years). Mean preoperative CD4+ T cell count was 340.5 cells/μL (range, 61-959). Four (80%) of the 5 patients for which data on viral load were available had values of <200 copies/mL. Six (85.7%) patients were receiving antiretroviral therapy and in 4 (66.6%), the treatment regime included protease inhibitors (PI). Two (28%) patients were co-infected with the hepatitis C virus.

All patients received a left internal mammary artery graft to the anterior descending coronary artery; saphenous vein grafts were used in the remaining vessels. One patient (14.3%) received a quadruple derivation, 2 (28.6%) a triple anastomosis, 3 (42.8%) a double anastomosis, and 1 (14.3%) a single anastomosis. Median sternotomy was the most commonly used approach, although in the patient who received the single anastomosis a left anterior minithoracotomy was used. Extracorporeal circulation (ECC) was employed in five (71.4%) of the 7 procedures.

HIV infection stage remained the same in all patients during follow-up. An increase in the CD4+ T cell count was observed in 4 patients for whom pre- and postoperative data were available (142.2±68.3 and 266±147.9 cells/μL, respectively). Viral load remained undetectable (<200 copies/mL) 1-3 months after the intervention. HAART was reintroduced when the patient recommenced taking food orally.

Comparison of HIV-Infected and Non-HIV-Infected Patients

All patients were male, and the mean age was lower in the group of HIV-infected patients (P<.05). The preoperative characteristics of both groups are shown in table 1 and intervention characteristics by study group in table 2.

Table 3 provides a summary of morbidity and mortality and the mean length of stay by study group. The overall index of postoperative complications was similar in both groups, although the number of complications per individual was slightly higher in non-HIV-infected patients. Four (57.1%) HIV-infected patients had postoperative complications: 2 had fever of unclear origin with negative blood cultures; 2 had persistent mediastinic hemorrhage with re-intervention required in 1 case; 1 had pneumonia caused by Haemophilus influenzae which resolved with antibiotic treatment, although mechanical ventilation was required, and; 1 had a urinary infection caused by Escherichia coli. The surgical wound did not become infected in any of the HIV-infected patients.

Twelve (57.1%) patients in the control group had postoperative complications: 3 had mediastinic hemorrhage which required re-intervention in 1 case; 2 had pneumothorax; 1 had hospital-acquired pneumonia, with no germ isolated; 1 had respiratory infection; 4 had fever of unknown origin requiring treatment with antibiotics, and which was probably catheter-related in 2 individuals; 3 had urinary infection; 1 had self-limited diarrhea; and 2 had surface infection of the surgical wound caused by Staphylococcus aureus which was sensitive to treatment with meticillin and coagulase-negative staphylococus; 1 patient had sternal instability with no germ isolated and with no need for re-intervention, and 1 had stroke.

Only 1 patient in the control group died from a ventricular arrythmia which was unrelated to the infectious process.

During follow-up, which was completed in 100% of cases (mean, 30.1 months; range, 10-70 months), all of the HIV-infected patients were in good clinical condition and did not require a further CAS.

DISCUSSION

The number of HIV-infected patients who receive an isolated CAS is small, so that there is a lack of data for this population. The characteristics of this population differ from those of HIV-infected patients receiving valve replacement surgery due to infectious endocarditis in our center, as they have a higher mean age, a lower number of injecting drug users, lower surgical risk,¹¹ and a EuroSCORE of <6 which places these patients in a low risk group with an expected mortality of 1.39%. The low surgical risk cannot be attributed to careful patient selection as all HIV-infected patients evaluated for surgery were included. There were few differences between HIV-infected and non-HIV-infected individuals receiving CAS, though HIV-infected patients were significantly younger.

HIV-infected individuals have traditionally been considered poor candidates for surgery because of poor prognosis, the risk of disease progression, and the risk of transmission to health-care personnel. Surgical outcomes in the patients analyzed in this study contradict this view, although the majority of studies report a slightly higher number of postoperative complications, even after minor surgical procedures, than that observed here in non-HIV-infected patients.^12-14

Previous experience in valve replacement surgery showed surgical responses to be adequate in HIV-infected individuals, independently of disease staging,¹¹ which is considered by some authors to be a contraindication for surgery. Outcomes with CAS in the present study were equally favorable.^6-8,11 We found that duration of ECC and aortic clamping were significantly lower in HIV-infected patients, although this did not produce differences in the levels of hospital morbidity and mortality and was due to a technical issue unconnected with the presence of HIV infection. The incidence, characteristics and severity of infectious complications were similar in both groups, and were independent of disease staging in the HIV-infected patients. Mortality was higher in non-HIV-infected patients, although as there was only one death, this finding lacks significance. The greater length of hospital stay observed in HIV-infected patients could be explained by the fact the diagnosing and treating complications in these patients is more complex.

It has been suggested that the negative impact of portease inhibitors on the short- and medium-term results of CAS in HIV-infected patients⁷ limit indications for surgery. In this study, there was no recurrence of angina, nor an increased need for angioplasty or revascularization in any of the HIV-infected patients during follow-up, although these results require confirmation in a larger sample with a longer follow-up period.

Cardiac surgery in general, and particularly ECC, have been associated with the progression of HIV infection,¹⁵ although more recent data, especially since the introduction of HAART, do not support this idea.^16,17 In this study, none of the HIV-infected patients showed disease progression, immunological deterioration, or increased viral replication after the intervention. However, the small sample size makes it difficult to determine whether there are advantages to employing ECC.

Limitations of the current study include the retrospective design, the small sample size and the fact that some patients were operated on without ECC. There were also significant differences in mean age between the 2 groups, principally because the age range for the control group was increased by ±10 years to account for the fact that HIV-infected patients develop ischemic heart disease earlier than the general population.

In conclusion, these results indicate that outcomes associated with isolated CAS in HIV-infected patients can be acceptable, and that there is no concomitant increase in morbidity or mortality, or disease progression.

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This work has been partially financed by the Red Temática Cooperativa de Grupos de Investigación en Sida (RIS) del Fondo de Investigación Sanitarias (FIS) and the Fundación Máximo Soriano Jiménez (Barcelona, Spain). No conflicts of interest are reported for any of the authors.



The members of Endocarditis Study Group are listed in the Appendix.



Correspondence: Dr. C.A. Mestres.

Servicio de Cirugía Cardiovascular. Hospital Clínic.

Villarroel, 170. 08036 Barcelona. España.

E-mail: [e-mail]

Received December 14, 2004.

Accepted for publication June 2, 2005.