Ann Thorac Surg 2004;78:129-134
© 2004 The Society of Thoracic Surgeons
Original article: cardiovascular
Impact of diabetes on outcome following isolated minimally invasive bypass grafting of the left anterior descending artery
Artur Lichtenberg, MDa*,
Uwe Klima, MD, PhDa,
Hans Paeschkea,
Max Pichlmaier, MDa,
Stefanie Ringes-Lichtenberg, MDb,
Thorsten Walles, MDa,
Heidi Goerler, MDa,
Axel Haverich, MD, PhDa
a Division of Thoracic and Cardiovascular Surgery Hannover, Germany
b Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
Accepted for publication December 29, 2003.
* Address reprint requests to Dr Lichtenberg, Hannover Medical School, Division of Thoracic and Cardiovascular Surgery, 30625 Hannover, Germany
e-mail: lichtenberg{at}thg.mh-hannover.de
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Abstract
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BACKGROUND: The outcome in patients treated by conventional coronary artery bypass grafting (CABG) for coronary artery disease is negatively influenced by the presence of diabetes. The relative effect of diabetes in patients undergoing isolated minimally invasive revascularization of the left anterior descending artery (LAD) using the internal thoracic artery (ITA) has as yet not specifically been looked at. Thus, this study sought to evaluate the impact of diabetes on mid-term outcome following minimally invasive coronary artery bypass grafting (MIDCAB).
METHODS: From 1996 to 1999, 411 patients received a MIDCAB procedure at our institution and were now followed up. In this study population there were 63 diabetic patients (15.3%) and 348 nondiabetic patients (84.7%). Isolated proximal stenoses or an occlusion of the LAD were present in 262 patients (63.7%), whereas 149 (36.3%) had multi-vessel disease (MVD) at the time of the MIDCAB procedure. The clinical outcome was evaluated by questionnaires sent to the patients and their physicians.
RESULTS: The mean follow-up was 29.4 ± 11.1 months. The incidence of myocardial infarction was significantly higher in diabetics as compared to nondiabetics (9.5% vs 3.2%, p = 0.034). Diabetics and nondiabetics had similar rates of subsequent revascularization procedures during follow-up. Cumulative total survival of diabetic and nondiabetic patients was not statistically different. The 3-year cardiac mortality was however significantly higher in diabetic than in nondiabetic patients if MVD was initially present (Kaplan-Meier estimate: 10.7% vs 2.5%, relative risk [RR] = 5.5, p = 0.017 by log-rank test). The 3-year cardiac mortality in diabetic and nondiabetic patients with isolated disease of the LAD (single vessel disease [SVD]) was not significantly different. After adjustment of baseline characteristics by Cox regression analysis the 3-year risk of cardiac death was significantly higher in the diabetic group (RR = 1.82, CI 95%:1.2 to 3.3, p = 0.045).
CONCLUSIONS: The results support diabetes to be an independent risk factor for outcome in patients with MVD undergoing a MIDCAB procedure in analogy to those undergoing CABG procedures. Diabetics with isolated disease of the LAD, however, benefit out of proportion from this treatment modality.
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Introduction
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Minimally invasive coronary artery bypass grafting (MIDCAB) is accepted as a safe and reliable surgical procedure for revascularization of proximally stenosed left anterior descending arteries [1]. It involves the utilization of the left internal thoracic artery (ITA) for bypass grafting through an anterolateral mini-thoracotomy. Cardiopulmonary bypass (CPB) is not required [2, 3]. Several studies have reported excellent short-term results following the MIDCAB procedure with low morbidity and mortality [1–5].
A number of long-term trials have identified predictors of mortality following conventional coronary artery bypass grafting using CPB. Among these factors, diabetes mellitus features as a significant negative predictor for long-term outcome [6–9]. Up to now there have been no studies to clarify the role of diabetes with respect to the intermediate and long-term outcome in patients following minimally invasive isolated left anterior descending artery (LAD) grafting on the beating heart using the ITA (MIDCAB).
In this study the impact of diabetes on outcome during in-hospital and mid-term observation of patients following MIDCAB was evaluated.
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Material and methods
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A total of 411 patients who underwent a MIDCAB procedure with isolated revascularization of the LAD using the ITA at our institution between June 1996 and December 1999 were included in the study. Five patients were lost to follow-up and were excluded from the analysis. A further 44 patients who underwent combined surgical and interventional ("hybrid") procedures (MIDCAB + angioplasty) were also not included.
Sixty-three patients (15.3%) had treated type 2 diabetes mellitus (30 insulin-dependent patients [7.3%]; 33 noninsulin dependent [8.0%]), and 348 patients (84.7%) were nondiabetics. Isolated proximal stenoses, or an occlusion of the LAD, were present in 262 patients (63.7%), whereas 149 (36.3%) had multi-vessel disease (MVD) at the time of the MIDCAB procedure. Of those with MVD, 102 patients (24.9%) had double-vessel and 47 (11.4%) had triple-vessel disease. All potential candidates for the MIDCAB procedure were evaluated preoperatively for ischemia in the area supplied by the LAD by their cardiologist using a variety of diagnostic methods (stress electrocardiogram [ECG], stress echocardiography, or nuclear methods). A clear clinical predominance of the LAD lesions in patients with MVD was carefully secured before their selection into the MIDCAB treatment group.
The reasons for the apparent incomplete revascularization in MVD patients have previously been elucidated in detail [3]. In summary, MVD patients with small vessels (< 1.0-mm diameter) unsuitable for bypass grafting with either a very limited target area of myocardial perfusion or extensive myocardial scarring in the right coronary or circumflex arteries (n = 69), stenoses less than 50% by diameter or long-term patency following angioplasty (n = 31) were scheduled for MIDCAB procedure. A combination of the aforementioned criteria was observed in 12 MVD patients. Thirty-three patients had extensive risk for CPB (n = 33), where complete multi-vessel, off-pump revascularization through a midline sternotomy appeared technically not achievable. Additionally, 4 MVD patients with a past history of sternal osteomyelitis with a leading LAD problem were also included in the MIDCAB program.
The surgical technique has previously been described in detail [2]. The left hemithorax was entered through the fourth or fifth intercostal space. The usual length of incision was 8 cm. The pedicle of the ITA was dissected from the caudal part of the sixth rib up to the cranial origin of the ITA under direct view. Exposure was obtained without rib resections by a Thora-LIFT Retractor (Vascular Therapies, Norwalk, CT). Side branches of the ITA were cut by electrocautery or clipped. A mechanical U-shaped stabilizer (CTS [Cupertino, CA] or ESTECH [Danville, CA]) was placed to both sides of the LAD. Antegrade blood flow was controlled by a tourniquet proximal to the chosen site of anastomosis. The LAD was incised longitudinally and the left ITA to LAD anastomosis performed using a running 8-0 polypropylene suture. For a better view of the vascular structures we used a blowing device (Medtronic, Grand Rapids, MI).
Demographic and in-hospital data of all MIDCAB procedures were collected and entered into the database. Baseline characteristic included age, sex, body mass index (BMI), and cardiac risk factors such as hypertension, smoking status, and hyperlipidemia. Comorbidity was defined as the presence of peripheral vascular disease, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), or chronic renal failure.
Early angiographic evaluation was principally intended for all patients. In cases of extensive risk for angiography the postoperative control angiography was omitted. Any other methods of quality control were not generally used.
Follow-up data were collected using a standardized questionnaire answered by the patients and their physicians or additionally by telephone interviews.
The study end points included total and cardiac-related late mortality (> 30 days following surgery), myocardial infarction, and need for subsequent revascularization. The criteria for myocardial infarction (MI) were a new onset of Q-waves or elevation of cardiac enzymes (creatinine kinase [CK] peak-levels and MB fraction) accompanied by an elevation of ST-segments in ECG examinations. A CK rise above two times the normal value without a new Q-wave on the ECG was considered a non-Q-wave MI.
Statistical analysis
The data are presented as mean ± standard deviation for continuous variables or number and percentages for dichotomous variables. Univariate analysis of categorical data were carried out using the X-square or Fisher exact tests. Univariate analysis of normally distributed continuous variables was carried out using the Student's t test. Kaplan-Meier estimates were used to calculate total and cardiac-related survival. Kaplan-Meier curves were compared using the long-rank test. Multivariate Cox regression analysis served to examine baseline characteristics to identify independent risk factors for cardiac mortality. The model included age, sex, body mass index, angina status, left ventricular ejection fraction, diabetes mellitus, history of smoking, hypertension, hyperlipidemia, comorbidities, and number of diseased vessels. A p value less than 0.05 was considered to indicate statistical significance. The SPSS statistical software package 11.0 for Windows (SPSS Inc., Chicago, IL) was used for analysis.
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Results
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Baseline characteristics
Demographic data and baseline characteristics of diabetic and nondiabetic patients are listed in Table 1.
The incidence of hypertension, hyperlipidemia, peripheral vascular disease, cerebrovascular disease, COPD, and renal failure was higher in diabetic patients compared to nondiabetics. Also, the diabetic group more often exhibited triple-vessel disease.
In-hospital outcome and control angiography
Table 2
depicts the in-hospital outcome of diabetic and nondiabetic patients following MIDCAB procedures. There was no statistical difference in the occurrence of in-hospital death, myocardial infarction, or stroke. The incidence of wound dehiscence and infection was low and similar in diabetic and nondiabetic patients.
Of all patients included in the study, 69% (n = 286) underwent control angiography, which was performed in 257 patients (62.5%) within 1 year of surgery and in 29 patients (7.1%) thereafter. The patency rate of ITA grafts was comparable between the study groups (Table 3).
Follow-up
All of the 411 patients were successfully followed up for 29.4 ± 11.1 months. Figure 1
illustrates the cumulative rates of total survival for the two subgroups of MIDCAB patients. The total 3-year mortality rate indicates a trend to be higher in diabetic compared with nondiabetic patients, but this difference achieved no statistical significance by Kaplan-Meier estimate (9.5% [6 patients] vs 4.3% [15 patients], relative risk [RR] = 2.21, p = 0.1 by log-rank test).
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Fig 1. Cumulative total survival of patients according to the presence or absence of diabetes. —— = diabetes; – – = nondiabetes. (D = diabetes; ND = nondiabetes.)
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However, diabetic patients had a significantly higher 3-year cardiac mortality rate when compared with nondiabetic patients (4.8% [3 patients] vs 1.2% [4 patients], RR = 4.1, p = 0.042 by log-rank test; Fig 2).
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Fig 2. Cumulative cardiac survival of patients according to the presence or absence of diabetes. —— = diabetes; – – = nondiabetes. (D = diabetes; ND = nondiabetes.)
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A comparison of cardiac-related mortality rates between diabetic and nondiabetic patients with respect to the number of diseased vessels reveals the significantly higher cardiac mortality rate in diabetic patients with MVD (10.7% [3 patients] vs 2.5% [3 patients], RR = 5.5, p = 0.017 by log-rank test). However, cardiac mortality rates compared between diabetic and nondiabetic patients with SVD were not different by Kaplan-Meier estimate (0% [0 patients] vs 0.4% [1 patient], p = 0.7 by log-rank test; Fig 3).
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Fig 3. Cumulative cardiac survival of diabetes patients according to the presence of MVD or SVD (isolated left anterior descending coronary artery lesion). —— = diabetes + SVD; - - - = nondiabetes + SVD; · · · = diabetes + MVD; – · – = nondiabetes + MVD. (D = diabetes; MVD = multi-vessel disease; ND = nondiabetes; SVD = single-vessel disease.)
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Table 4
depicts incidence of recurrent angina, ongoing medication for angina, cumulative rates of myocardial infarction, and subsequent revascularization during follow-up. Diabetics had similar rates of recurrent angina compared to nondiabetics but significantly more antianginal medication (33.3% vs 20.4%, p = 0.032). The incidence of myocardial infarction was significantly higher in diabetics compared to nondiabetics (9.5% vs 3.2%, p = 0.034). Diabetics had similar rates of percutaneous transluminal coronary angioplasty (PTCA) or bypass surgery during follow-up compared with nondiabetics.
Multivariate Cox regression analysis revealed diabetes as an important independent predictor of 3-year cardiac mortality (RR = 1.82, CI 95%: 1.2 to 3.3, p = 0.045).
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Comment
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During the last decades all long-term trials emphasize the importance of diabetes mellitus in the short- and long-term outcome of coronary artery disease (CAD). Thus, diabetes is a major risk for the progression of arteriosclerosis resulting in a variety of different cardiovascular disorders and comorbidities including diastolic dysfunction, abnormality of vascular reactivity, renal insufficiency with arterial hypertension, etc.
Patients suffering from diabetes mellitus have a greater incidence of atherosclerotic coronary artery diseases, which, when present, is associated with increased morbidity and mortality compared with nondiabetics [7–10]. Diabetes has been proven to be an independent risk factor for a more rapid and diffuse progression of arteriosclerosis in all published series on surgical and interventional treatment [10–13]. Various trials have reported that diabetic patients with MVD have a significantly higher risk of late mortality and morbidity following coronary artery bypass grafting [14–16]. Similarly, our patients with treated diabetes and MVD had a poorer survival due to cardiac causes than nondiabetics at 3 years postoperatively. The difference in mid-term survival is hereby not driven by operative mortality but by late events.
In current studies, the diabetic groups demonstrate a significant benefit from the use of the ITA graft due to the superior long-term patency compared with SVG. Thus, 7-year survival rates in diabetics following surgery using the ITA was 83.2% (BARI). In contrast, patients with vein grafts revealed a 7-year survival of only 54.5% [17]. The angiographic evaluation of bypass grafts in patients following coronary bypass surgery (4-year follow-up) in the BARI trial demonstrated that diabetic patients had similar patency rates of the ITA (89%) as compared to those without diabetes (85%) [18].
Unfortunately, recent large randomized trials such as BARI, EAST, or ARTS, where long-term outcomes following interventional and surgical revascularization were compared, have been subject to the criticism, because a variety of different surgical techniques (number and type of bypass grafts) were applied [10–12]. Our patients however, received identical, standardized initial procedures with isolated LAD grafting using the left ITA. Despite the comparatively smaller patient population and the limited follow-up period of 3 years, the generally poorer outcome in diabetic patients was confirmed. This is true in light of the best graft material being utilized. In patients with lone LAD disease however, the presence of diabetes does not seem to influence the outcome following MIDCAB.
Surgical revascularization of stenotic non-LAD vessels in diabetics with double- or triple-vessel disease was deemed either impossible or ineffective for the previously mentioned reasons. We acknowledge, that complete revascularization must be the aim of coronary artery bypass surgery and remains one of the most important factors for long-term results following surgery [19]. Recent investigations [10–12] confirm that diabetic patients profit from surgical revascularization of graftable, stenotic, terminal coronary vessels. Additionally, due to poorer long-term results following interventional procedures compared to bypass surgery, surgical revascularization is often the last chance for such patients to attempt a long-term restoration of perfusion in marginal stenotic arteries. The diabetic patients with MVD in our study population with additional diseased non-LAD vessels not amenable to surgery or cardiological intervention the concept of complete revascularization was not applicable. In both our groups an occurrence of restenosis following previous angioplasty or high risk lesions of the proximal LAD (ACC/AHA lesion classification system [20]) were the main indications for the surgical revascularization of the LAD. The cardiologic interventions for the LAD lesion in these patients, especially in diabetics, are primarily associated with a high procedural risk as well as a high risk for a subsequent restenosis with a probability of a surgical revascularization [12, 17]. The fact that cardiologic interventions are accompanied by a higher incidence of repeat interventions as well as with a lower freedom from angina due to occurrence of the restenosis as compared to the MIDCAB procedure [1] emphasizes the superiority of the surgical approach in patients with the LAD as only target vessel for revascularization. In our opinion, diabetic patients with MVD and morphologic impossibility of complete revascularization or with unacceptably high risk for conventional bypass surgery due to other organ dysfunction or insufficiency, active malignances, systemic immunosuppression, or previous sternal osteomyelitis [3]. The LAD revascularization using the ITA by a MIDCAB approach is the safe treatment despite the elevated late mortality when compared with diabetics with lone LAD disease.
Limitations
The authors recognize limitations in the design and the interpretation of the present study. It is an observational clinical study. The follow-up data were collected retrospectively. An objective evaluation to the progression of the coronary disease, such as myocardial viability studies or serial angiographic examinations, were not performed. The effectiveness of diabetic control during follow-up was not assessed specifically.
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Conclusions
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Treatment of a proximal high-grade LAD lesion by MIDCAB in diabetic patients is safe and effective. From a patient management point of view we conclude that diabetic patients with single-vessel disease of the LAD should be recruited for MIDCAB as first choice of treatment. In MVD patients where the LAD is the only target vessel for interventional or surgical treatment again ITA grafting in the form of a MIDCAB procedure is the safe treatment modality. From the literature this is especially true for the diabetic patient where the long term superiority of ITA grafting over interventional procedures has been well established.
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Abstract
Introduction
