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- Materials and Methods
Coronary artery disease (CAD) is a significant public health concern , and its incidence among potential lung transplant recipients is likewise not uncommon. It is estimated that over half of patients with advanced lung disease have occult CAD , and the prevalence in lung transplant candidates is expected to increase with higher proportions of elderly patients referred for transplantation . In general, CAD is felt to be a relative contraindication to lung transplantation for several reasons. The limited availability of donor organs mandates strict selection criteria to optimize allocation of this precious resource [4, 5]. In addition, the potential for accelerated atherosclerosis in the setting of chronic immunosuppression and other drug therapy has led to patient exclusion from the lung transplant process .
The feasibility of coronary revascularization either by percutaneous coronary intervention (PCI) prior to transplant, or concomitant coronary artery bypass grafting (CABG) at the time of transplant, has previously been described [7-11]. As advances in lung transplantation continue to expand the donor pool [12-14] and improve outcomes in high-risk recipients , it is increasingly likely that transplant teams will need to address occult CAD in lung transplant candidates.
At our center, we have performed coronary revascularization either by PCI or CABG on a carefully selected group of lung transplant recipients who do not have other significant comorbidities. Left ventricular function is documented to be normal and each case is reviewed by the lung transplant surgeon to determine the best revascularization strategy. We have previously reported our early experience with this approach .
In the current study, we report our expanded experience with coronary revascularization in lung transplant recipients with concomitant CAD, which includes the largest series of simultaneous lung transplant and CABG reported in the literature. Our objective is to analyze intermediate-term outcomes and need for coronary reintervention in this patient population compared with control subjects. We hypothesize that in carefully selected recipients with isolated, discrete, CAD and preserved left ventricular function, lung transplantation and concomitant revascularization can be performed with acceptable outcomes and similar intermediate-term survival to those recipients without CAD.
- Top of page
- Materials and Methods
Concomitant CAD in patients evaluated for lung transplantation is not uncommon given the longer life expectancy for the general population and shared risk factors in the pathogenesis of end-stage lung disease and CAD, such as tobacco use. The current analysis comparing combined lung transplant and CABG to preoperative PCI and controls without CAD demonstrates equivalent survival as well as similar odds of cardiac or noncardiac adverse postoperative events; however, CABG recipients required longer intensive care unit stay, hospital stay and ventilator support. Rates of additional revascularization procedures after transplant were also similar between CABG and PCI groups. Importantly, subgroup analysis of patients over/under age 65 in the CABG group demonstrated shorter survival in the older cohort, though the small numbers for this sample precluded statistical comparison.
Our results contribute to an increasing body of literature demonstrating acceptable outcomes with combined lung transplant and CABG in selected recipients. Early reports in 2001–2003 demonstrated feasibility of concurrent CABG both on and off pump; however, the sample size in these series precluded definitive conclusions [9, 25, 26]. More recently, Sherman et al  reported their experience with 27 patients undergoing either CABG or PCI prior to transplant. They found similar results compared with controls, including hospital length of stay, complication rates, need for reintervention and survival at a mean follow-up of 3 years. Our results support equivalent survival and adverse events in risk-adjusted analysis of recipients with concurrent CABG; however, these patients required substantially more hospital resources including longer intensive care unit and hospital length of stay as well as days requiring mechanical ventilation. Despite equivalent survival, this more tenuous postoperative course is concerning, and therefore in accordance with these results, our current practice is to preferentially perform preoperative PCI with bare metal stents if technically feasible (exceptions may include left main disease and inability to tolerate anti-platelet therapy). The current guidelines by American College of Cardiology Foundation and the American Heart Association provide a Class 1 recommendation for CABG to improve survival in patients with significance stenosis of the left main coronary artery; however, they do note that PCI may be a reasonable alternative in selected patients . Randomized control trials to evaluate this topic are few. The prospective randomized trial titled “Study of Unprotected Left Main Stenting Versus Bypass Surgery” (LE MANS Study NCT00375063) suggested that PCI may have favorable early outcomes in comparison with CABG; however, each treatment group was limited to approximately 50 patients and long-term data are not yet available . In a randomized trial comparing CABG versus PCI for 1800 patients (SYNTAX trial NCT00114972), a prespecified subgroup analysis of 705 patients with left main disease demonstrated comparable safety and efficacy at 1 year; however, the authors noted the need for longer follow-up to confirm these findings . As the data evaluating PCI for left main disease continue to evolve with the accumulation of long-term follow-up, moving forward this may prove to be a reasonable treatment option in the lung transplant population.
The use of an arterial graft when performing concomitant lung transplant and CABG has been debated [25, 27]. The rationale for the use of vein graft is the expectation that the median survival of a lung transplant recipient is generally reported to be in the order of 6 years while in the general cardiac literature vein grafts have been found to be durable for at least that length of time . Although we chose an individual approach for each patient, our preference is to use the mammary graft when possible and we have found it to be technically feasible regardless of the surgical approach (sternotomy, thoracotomy and clamshell). Although the number of patients in our CABG series requiring reintervention is small, it is interesting to note that with the exception of a single patient who suffered a variety of postoperative complications, none of the patients with arterial grafts required reintervention. In contrast, the remaining four patients who did require an intervention demonstrated failure of their vein conduit.
Lung transplant is increasingly performed in elderly recipients , and accordingly, CAD is more likely to be encountered in this population. Our results demonstrate the numerically decreased survival in concurrent CABG recipients over age 65. The limited sample size precludes statistical comparison or definitive comments on survival differences in this cohort; however, this is nonetheless a concerning finding. The reasons for lower survival in the older cohort are not entirely clear. Contributing factors may include the increased technical demands of concomitant CABG, longer operative and ischemic times and decreased maximal graft performance. Age-related comorbidities such as atherosclerotic disease and impaired renal reserve may also play a role. Given these concerns, we currently do not offer concomitant CABG to patients over age 65 and recommend exercising caution with concomitant coronary revascularization in this population.
It is important to note that shorter waitlist times were observed in the CABG and PCI groups (median 12 days for both) compared with controls (median 70 days). The most frequent diagnosis for the CABG and PCI groups was pulmonary fibrosis (67% and 63%, respectively) compared to 36% of patients in the control group with this diagnosis (the most common diagnosis for controls was obstructive disease at 43%). The CABG and PCI groups were also significantly older (median age 62 and 64 years, respectively) compared with controls (median age 55 years). These factors likely contribute to the shorter waitlist time observed in the CABG and PCI groups. Additionally, patients with concomitant CAD demonstrated higher rates of functional status requiring assistance (data not shown), which is also factored into the Lung Allocation Score.
There are inherent limitations to this study, which should be considered when interpreting these results. This is a retrospective review, and therefore unmeasured confounders may exist. Patients excluded from transplant due to cardiac evaluation are not tracked in our system and therefore unavailable for analysis. Outcome measures do not include qualitative metrics, such as quality of life. Additionally, our follow-up is limited to intermediate-term (2.7-year median follow-up time for the CABG group) and long-term follow-up data (≥5 years) are currently unavailable.