HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Sandra Fraund Georg Lutter Michael Brandt Jochen Cremer Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fraund, S. Articles by Cremer, J. Search for Related Content PubMed PubMed Citation Articles by Fraund, S. Articles by Cremer, J. Related Collections Coronary disease

Ann Thorac Surg 2005;79:1225-1231
© 2005 The Society of Thoracic Surgeons

---

Original articles: Cardiovascular

Midterm Follow-Up After Minimally Invasive Direct Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention Techniques

^a Department of Cardiovascular Surgery, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany
^b Department of Cardiology, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany
^c Institute for Biometry and Medical Statistics, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany

Accepted for publication August 23, 2004.

^_* Address reprint requests to Dr Fraund, Department of Cardiovascular Surgery, University of Schleswig-Holstein, Campus Kiel, Arnold Heller Str 7, 24105 Kiel, Germany (E-mail: sfraund{at}kielheart.uni-kiel.de).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment References

 
BACKGROUND: Revascularization of the left anterior descending coronary artery can be performed by minimally invasive direct coronary artery bypass grafting (MIDCAB) or percutaneous coronary intervention techniques (PCI). The study compared the midterm results of both techniques.

METHODS: The outcome of 206 consecutive MIDCAB and 256 PCI patients treated from 1998 until 2001 was retrospectively analyzed. Cardiologists determined the primary patient allocation for the distinct revascularization technique. Periprocedural complications and midterm follow-up, including quality-of-life assessment (SF-36), was reported up to 5.2 years (3.4 ± 0.7 years).

RESULTS: Periprocedural and overall mortality (p = 0.206) showed no differences. Four MIDCAB patients required early reoperation but not for repeated target vessel revascularization. In 16 patients secondary PCI (7.8%) of other coronary vessels was performed. Repeated revascularization of the left anterior descending coronary artery was necessary in 24.2% of patients in the PCI group (p < 0.001), with 4.7% finally requiring surgical revascularization. The incidence of major adverse cardiac events, including myocardial infarction (p = 0.581), repeated target vessel revascularization (p < 0.001), or death (p = 0.206) was higher in the PCI group. This difference consisted basically of the need for repeated target vessel revascularization. Patient-based quality-of-life assessment (SF-36) was independent from the primary chosen revascularization method.

CONCLUSIONS: At midterm follow up, MIDCAB resulted in significantly superior results regarding the need for repeated target vessel revascularization compared with PCI, with no significant differences regarding other major cardiac events.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment References

 
A study by Goy and colleagues published in 1999 showed that surgical and angioplasty revascularization techniques improved the long-term survival of patients with dominating stenosis of the left anterior descending (LAD) coronary artery [1]. After its clinical introduction, minimally invasive direct coronary artery bypass grafting (MIDCAB) proved to be a less invasive surgical option for revascularization of the LAD [2–4] compared with conventional coronary artery bypass grafting (CABG).

In recent years, different groups have compared the MIDCAB approach with percutaneous coronary intervention techniques (PCI). They demonstrated that CABG surgery and angioplasty or stent-grafting have comparable rates for associated periprocedural mortality and myocardial infarction and stroke [5, 6]. However the left internal thoracic artery (LITA)–LAD bypass appeared superior regarding the need for repeated target vessel revascularization (TVR) [7].

Despite these encouraging results, the number of MIDCAB operations performed in Germany was decreasing in recent years. Even though some of these studies had a prospective, randomized study design, they were disadvantaged by rather small patient groups and a limited follow-up. Therefore, we retrospectively analyzed 462 patients with predominating LAD stenosis, who underwent either MIDCAB grafting or angioplasty/stent-grafting (PCI), with a follow-up over a 5-year period that included a quality-of-life assessment.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment References

 
Patients that had been treated between September 1998 and December 2001 by MIDCAB (MIDCAB group) or percutaneous coronary angioplasty/stent (PCI group) at the University of Schleswig-Holstein, Campus Kiel were selected for the study. Each patient had predominantly angiographically documented LAD stenosis with a 70% or greater diameter loss or complete occlusion of the LAD. In a few patients this was combined with significant or insignificant additional stenoses of other vessels (two-vessel coronary artery disease [CAD II]: MIDCAB, 28.6%; PCI, 25.8%; CAD III: MIDCAB, 14.1%; PCI, 8.6%). One surgeon performed all MIDCAB group operations.

According to the institution's general practice, patients were stratified for treatment by the referring cardiologist. PCI was offered as the primary treatment option; MIDCAB was regularly the second option when PCI was unsuccessful or technically risky.

Baseline Data
Altogether, 462 patients were analyzed: MIDCAB, 206 patients; PCI, 256 patients (67 with plain dilatation and 189 with stent-grafting including atherectomy). Patient groups are listed according to special cardiovascular risk profile and baseline demographics in Tables 1 and 2.

Follow-Up (SF-36 Score)
The SF-36 has 36 short questions representing health status and quality of life in eight different categories: I physical functioning, II physical role, III bodily pain, IV general health, V vitality, VI social functioning, VII emotional role, and VIII mental health. Raw points were transformed, generating a score for each dimension ranging from 0 to 100, with 100 reflecting best function [8].

The groups were statistically investigated according to revascularization methods (MIDCAB vs PCI), but also in subgroups to compare different factors: the presence of hypertension, diabetes, body mass index (BMI) more than 30 kg/m², age more than 70 years, and sex. The groups were compared for major adverse cardiac events (MACE), including death, myocardial infarction, and repeated TVR at the April 30, 2003 endpoint.

Data Analysis
Data were analyzed with the Statistical Package for Social Sciences (Version 11) (SPSS, Chicago, IL). Univariate comparison between MIDCAB and PCI patients for different preoperative, perioperative, and postoperative demographic data was calculated by ² or the Fisher exact test; p values of 0.05 or less were considered to reach statistical significance. Data of SF-36, which assigns different items into a scale with values ranging from 0 to 100, were compared by the Wilcoxon test. Time to event (MACE) was calculated from the day of operation/intervention until the first MACE or until April 30, 2003 (date of end of the survey). These data were analyzed with the Kaplan-Meier method.

To account for a possible bias based on the heterogeneity of the groups, a second analysis included preoperative data in a logistic regression analysis to form a propensity score. This analysis comprised preoperative data on renal insufficiency, chronic obstructive pulmonary disease, peripheral occlusive disease, hypertension, hyperlipidemia, diabetes mellitus, obesity, sex, the presence of multivessel disease, myocardial infarction or left main stenosis, previous cardiac surgery or PCI of LAD, unstable angina, atrial fibrillation, reduced left ventricular ejection fraction, preoperative intraaortic balloon pump (IABP), and localization of LAD stenosis. A log-rank test with stratification after propensity score classes was performed for a final comparison in survival, repeated target vessel revascularization by PCI, or surgical and overall MACE.

MIDCAB Revascularization Technique
Anesthesia in the MIDCAB group followed a total intravenous anesthesia protocol. Intraoperative monitoring included an electrocardiogram recording with ST-segment analysis, continuous arterial and pulmonary arterial pressures, cardiac output, intermittent blood gas analysis, and body temperature measurements. Single-lung ventilation was established. Anesthesia was gradually reduced during closure of the chest wound. Since February 1999, immediate extubation at the end of surgery has been attempted [9]. All patients underwent surgery in a standardized method as described earlier [10]. Postoperative medication in the MIDCAB group routinely included a 100-mg daily dose of aspirin.

PCI Revascularization Technique
PCI was carried out through a right or left femoral access. Guiding catheters (8F) were introduced. The coronary arteries were intubated with 0.014-inch guide wires, and matched-size balloon catheters were used to dilate lesions. Stents were selected according to the morphology of the LAD lesion. Stents used were the GFX (24, 18, 12, and 8 mm) (Arterial Vascular Engineering, Santa Clara, CA); Crossflex (25, 15, and 4 mm) (Cordis, Miami, FL), and MultiLink (25, 18, 15, and 7 mm) (Guidant, Indianapolis, IN). Implantation was performed with 3.0-mm and 4.0-mm balloons, applying pressures between 7 and 16 bar.

PCI was considered successful if the stenosis was reduced to less than 30%, as judged by a visual estimation of the postintervention angiogram, and if ischemia or chest pain was absent. Four to 6 hours after PCI, a closing system (VasoSeal, Datascope Corp, Mahwah, NJ; Angio-Seal, St. Jude Medical, Minneapolis, MN) was fixed at the puncture site. Anticoagulation initially consisted of 10,000 IU heparin controlled by an activated clotting time of between 300 and 350 seconds, followed by ticlopidine (250 to 500 mg) for 3 months and then aspirin as single medication.

	Results

Top Abstract Introduction Patients and Methods Results Comment References

 
The study comprised 462 patients (MIDCAB, 206 patients; PCI, 256 patients). More patients with previous cardiac surgery (p < 0.001) and preceding interventional LAD treatment (p < 0.001) were in the MIDCAB group. Additionally, more MIDCAB patients had a severely reduced left ventricular function preoperatively (30%; p < 0.001) and a deleterious peripheral vascular status (p = 0.003). Left main coronary artery stenosis was only present in the MIDCAB patients (8.2%; p < 0.001), and in 26.6% of the patients the LAD lesion was in the middle-to-distal part of the vessel. The detailed demographics are presented in Tables 1 and 2.

Early Clinical Outcome
MIDCAB GROUP
All operations were performed without conversion to sternotomy. Immediate postoperative extubation was possible in 150 of 206 (72.8%) patients, with 56 (27.2%) transferred on the day of operation from the intensive care unit (ICU) and 191 (92.7%) within 24 hours after operation. Three patients (1.5%) needed prolonged ventilation with extended ICU stay: 2 had pulmonary complications and hemodynamic instability because of intermittent atrial fibrillation and 1, who was 81 years old, had pulmonary hypertension with ischemic cardiomyopathy. Other specific postoperative complications included rethoracotomy for bleeding or left internal thoracic artery (LITA) dehiscence (Table 3), hemiplegia 3 days postoperatively, enzymatically documented myocardial infarction, and 1 patient had a pulmonary artery embolism. In-hospital mortality was 1.5% (3/206). One 83-year-old patient died from multiorgan failure (acute myocardial infarction and preoperative implantation of an IABP), 1 died after resuscitation (autopsy showed LITA dehiscence preceding or following the resuscitation), and 1 died from respiratory failure after pneumonia.

Local problems at the access site occurred in both groups (Table 3). Ten (4.8%) of MIDCAB patients had minor wound healing problems/hematoma and a hernia developed in 1 patient during the follow-up. Major complications in the PCI group were arteriovenous fistula, development of a false aneurysm, need for operative reconstruction of the femoral artery, and ischemia-like syndrome in follow-up because of scar tissue. Extensive hematoma at the puncture site was frequent (12.8%).

Midterm Follow-Up and Analysis of MACE
At midterm follow-up (3.4 ± 0.7 years), 11 additional patients of the MIDCAB group (5.3%) and 10 patients of the PCI group (3.9%) had died (p = 0.506), resulting in no statistically significant difference in overall mortality between the groups (6.8% vs 3.9%; p = 0.206) (Fig 1). Specific reasons for the 11 deaths in MIDCAB group were cardiac causes in 6 patients consisting of endocarditis of aortic valve prosthesis (1), congestive heart failure (4), and sudden death with normal bypass morphology in autopsy (1). Noncardiac causes in the remaining 5 patients were cancer (2), pulmonary emphysema (1), suicide (1), and stroke (1).

View larger version (15K): [in this window] [in a new window]   Fig 1. Survival. Kaplan-Meier estimates for survival of percutaneous coronary artery intervention (PCI, dashed line) patients and of minimally invasive direct coronary artery bypass (MIDCAB, solid line) patients. There is no overall difference in mortality (p = 0.206) between the groups at midterm follow-up (3.4 ± 0.7 years).

Table 4 summarizes the major in-hospital and follow-up complications and MACE for both groups. In 16 (7.8%) MIDCAB patients, PCI for stenoses other than the LAD (6 of the right coronary artery, 10 of the circumflex artery) was performed in most as a primary intended hybrid procedure. None of the MIDCAB patients needed interventional or surgical revascularization for recurring anterior wall ischemia. One patient needed reoperation for an ascending aneurysm that was due to chronic type A-dissection.

View larger version (15K): [in this window] [in a new window]   Fig 2. Need for repeated target vessel revascularization by percutaneous coronary artery intervention (PCI). In the PCI (dashed line) group, the need for repeated revascularization of the left anterior descending artery (target vessel revascularization by PCI) is significantly higher (p < 0.001) than in minimally invasive direct coronary artery bypass (MIDCAB, solid line) patients at midterm follow-up (3.4 ± 0.7 years).

Control angiography performed in 119 (57.8%) of the MIDCAB patients after 42.54 ± 57.16 days demonstrated a 100% graft patency rate in this small cohort. The reangiography rate in the PCI group was 61.7% after a mean period of 133.9 ± 158.4 days.

Quality of Life
The SF-36 was completed by 80% of the patients in both groups. The MIDCAB and PCI patients had similar responses to the different categories of the SF 36 questionnaire. Figure 3 shows the results in 8 different categories. Further analysis of diverse subgroups independent of the revascularization technique, such as patients with a BMI of more than 30 kg/m^2,, the presence of diabetes mellitus, hypertension, age more than 70 years, sex, and even repeated PCI also revealed no significant difference for the specific quality-of-life categories.

View larger version (12K): [in this window] [in a new window]   Fig 3. SF-36 health survey quality-of-life assessment of minimally invasive direct coronary artery bypass patients (black square) versus percutaneous coronary artery intervention patients (white triangle) in eight categories: I physical functioning (p = 0.785); II physical role (p = 0.950); III bodily pain (p = 0.392); IV general health (p = 0.636), V vitality (p = 0.630), VI social functioning (p = 0.458), VII emotional role (p = 0.280), VIII mental health (p = 0.741).

	Comment

Top Abstract Introduction Patients and Methods Results Comment References

As it is influenced by immediate extubation after the MIDCAB procedure [9], with early transfer of the patient from the intensive care unit (ICU) to the regular ward, the length of stay on ICU is not different from that of less invasive PCI-techniques. This would allow for a substantial reorganization of ICU management to achieve major cost savings and a more efficient use of capacities. However, MIDCAB patients still have a longer in-hospital stay than PCI patients (7.4 ± 3.2 days vs 3.4 ± 3.5 days, p < 0.001), with the need for further improvement in future. Even though stenting was shown to be more expensive than plain angioplasty, PCI is still less expensive than MIDCAB in regard to the length of stay and total hospital charges [13]. With increasing use of drug-eluting stents, this should be critically reevaluated in the near future.

When we compared the quality-of-life scores, including different factors such as physical functioning, general health, social, and emotional role, both revascularization strategies were equally effective. Neither the more invasive surgical trauma nor the need for repetitive interventional therapy of the LAD in the PCI group contributed to a significant difference in patients' self-obtained assessments of quality of life. This might well reflect patients coping with the revascularization by using their physicians' recommended strategies. The CABG operation was shown to improve patient quality of life in a prospective study [14].

Whether PCI or surgery is the optimal treatment for LAD stenosis is still controversial. In our study we could demonstrate the superiority of surgery in terms of a significantly lower incidence of the need for repeated TVR. Additionally, the MIDCAB cohort consisted of higher-risk patients as determined by preoperative variables such as renal insufficiency, low ventricular ejection fraction, peripheral occlusive vascular disease, reoperations, left main stenosis, and more distally located LAD stenosis or even occlusion. To analyze this variability, we repeated the analysis of special outcome data using patient matching by propensity score. By applying this statistical method, we tried to overcome the retrospective design of the study and reflect the clinical reality in our department. We could demonstrate that in midterm follow-up, there is a clear advantage for MIDCAB surgery regarding the need for repeated TVR either by interventional or operative methods. But we also demonstrated that there is no significant difference in short-term or long-term survival, myocardial infarction, or quality of life; therefore, the significant differences in MACE between both groups is predominantly based on the single event of need for repeated TVR.

Further attention should be paid to the fact that MIDCAB offers a revascularization strategy beyond the treatment of proximal LAD stenosis, for which both PCI and MIDCAB maybe similarly applicable. The MIDCAB revascularization can also be liberally offered for occluded vessels, distal stenoses, small vessels, and selected cases of left main stenoses. For the latter situation, PCI applicability is regarded as rather restrictive.

Another aspect is the policy in Germany of patient selection for surgery or PCI techniques. As cardiologists are usually the first physicians to judge the possibility of interventional revascularization, MIDCAB is normally the second choice. Special attention must be paid to the fact that the MIDCAB expertise in our institution is highly elaborated. Thus, this patient group includes patients in which MIDCAB was intended to be the ultimate therapy in a multimorbid state because conventional surgery was regarded as too risky.

It can be speculated that in a randomized prospective study of patients with classic LAD stenosis, the superiority of surgery might be even more evident, leading to the provocative thesis that MIDCAB in hands of experienced surgeons should be regarded as a primary option in patients with LAD stenosis with the prospect of better long-term success rates, especially in the presence of angiographically documented patency rates of 98% and more [4, 15]. In 1999 Goy and colleagues showed that CABG or angioplasty were similarly effective in the treatment of isolated LAD stenosis in the early postoperative period, but the CABG-group showed a superior freedom from revascularization procedures up to 5 years [16]. Additionally, Drenth and colleagues showed a trend in favor of surgery for major adverse cardiac and cerebrovascular event-free survival at 3-year follow-up in their prospective trial for high-grade LAD stenosis [17].

Given these favorable MIDCAB results—even in demanding clinical situations with multimorbid patients and complex coronary lesions—treatment policy and patient stratification should be rediscussed. It no longer seems justified to propose surgery just as a secondary option for the treatment of LAD lesions.

Study Limitations
One major limitation of the study is the retrospective and nonrandomized design. Another area is the allocation of patients for the different revascularization strategies. Usually, the cardiologists distinguish between the patients for those who are good PCI candidates without regularly involving a surgeon in further consultation, and a minority of patients are discussed for surgery because of a primary PCI that was unsuccessful or because they missed eligibility for PCI. Therefore, the study groups were heterogeneous and a selection bias had to been taken into account. To reflect the clinical reality and to exclude this source of error, we applied a propensity score for the different MACE events. This caused a reduction of included patients but analysis affirmed the main statement of a higher incidence of MACE in the PCI group, which resulted mainly from the need for repeated target vessel revascularization.

In addition, there are new gains in the PCI field regarding use of glycoprotein IIb/IIIa receptor blockers and improved stent designs, especially the new era of drug-eluting stents. In the future, prospective randomized study trials will be necessary to compare more actual treatment strategies.

	References

Top Abstract Introduction Patients and Methods Results Comment References

1. Goy JJ, Eeckhout E, Moret C, et al. Five-year outcome in patients with isolated proximal left anterior descending coronary artery stenosis treated by angioplasty or left internal mammary artery graftingA prospective trial. Circulation 1999;99:3255-3259.[Abstract/Free Full Text]
2. Calafiore AM, Di Giammarco G, Teodori G, et al. Left anterior descending coronary artery grafting via left anterior small thoracotomy without cardiopulmonary bypass Ann Thorac Surg 1996;61:1658-1663.[Abstract/Free Full Text]
3. Subramanian VA, McCabe JC, Geller CM. Minimally invasive direct coronary artery bypass grafting: two year clinical experience Ann Thorac Surg 1997;64:1648-1653.[Abstract/Free Full Text]
4. Cremer J, Mügge A, Wittwer T, et al. Early angiographic results after revascularization by minimally invasive direct coronary artery bypass (MIDCAB) Eur J Cardiothorac Surg 1999;15(4):383-387.[Abstract/Free Full Text]
5. Diegeler A, Spyrantis N, Matin M, et al. The revival of surgical treatment for isolated proximal high-grade LAD lesions by minimally invasive coronary artery bypass grafting Eur J Cardiothorac Surg 2000;17:501-504.[Abstract/Free Full Text]
6. Mariani M, Boonstra PW, Grandjean JG, et al. Minimally invasive coronary artery bypass grafting versus coronary angioplasty for isolated type C stenosis of the left anterior descending artery J Thorac Cardiovasc Surg 1997;114(3):434-439.[Abstract/Free Full Text]
7. Cisowski M, Drzewiecki J, Drzewiecki-Gerber A, et al. Primary stenting versus MIDCAB: preliminary report—comparison of two methods of revascularization in single left anterior descending coronary artery stenosis Ann Thorac Surg 2002;74:1334-1339.
8. Bullinger M. German translation and psychometric testing of the SF-36 health survey: preliminary results from the IQOLA Project Soc Sci Med 1995;41:1359-1366.
9. Fraund S, Behnke H, Böning A, Cremer J. Immediate postoperative extubation after minimally invasive direct coronary artery surgery (MIDCAB) Interactive Cardiovasc Thorac Surg 2002;1:41-45.[Abstract/Free Full Text]
10. Cremer J, Wittwer T, Böning A, et al. Minimally invasive coronary artery revascularization on the beating heart Ann Thorac Surg 2000;69:1787-1791.[Abstract/Free Full Text]
11. Cameron AC, Green GE, Brogno DA, Thornton J. Internal thoracic artery grafts: 20 year clinical follow up J Am Coll Cardiol 1995;25:188-192.[Abstract]
12. Boylan MJ, Lytle BW, Loop FD, et al. Surgical treatment of isolated left anterior descending coronary artery stenosis: comparison of left internal mammary artery and venous autograft at 18 to 20 years follow up J Thorac Cardiovasc Surg 1994;107:657-662.[Abstract/Free Full Text]
13. Fry ETA, Hermiller JB, Lips DL, et al. Comparison of stents, bypass surgery (CABG) and minimally invasive bypass (MIDCAB) for isolated LAD revascularization: patient selection, outcomes, and costs[abstract] Circulation 1995;92((Suppl):I-324.
14. Caine N, Harrison SCW, Sharples LD, Wallwork J. Prospective study of quality of life before and after coronary artery bypass grafting BMJ 1991;302:511-516.
15. Mack MJ, Magovern JA, Acuff TA, et al. Results of graft patency by immediate angiography in minimally invasive coronary artery surgery Ann Thorac Surg 1999;68:383-390.[Abstract/Free Full Text]
16. Goy JJ, Eeckhout E, Moret C, et al. Five-year outcome in patients with isolated proximal left anterior descending coronary artery stenosis treated by angioplasty or left internal mammary artery grafting Circulation 1999;99:3255-3259.
17. Drenth DJ, Veeger NJ, Winter JB, et al. A prospective randomized trial comparing stenting with off-pump coronary surgery for high-grade stenosis in the proximal left anterior descending coronary artery: three year follow up J Am Coll Cardiol 2002;40(11):1955-1960.[Abstract/Free Full Text]

This article has been cited by other articles:

				V. Falk and F. W. Mohr Minimally Invasive Myocardial Revascularization Card. Surg. Adult, January 1, 2008; 3(2008): 697 - 710. [Full Text]

				Z. Jaffery, M. Kowalski, W. D. Weaver, and S. Khanal A meta-analysis of randomized control trials comparing minimally invasive direct coronary bypass grafting versus percutaneous coronary intervention for stenosis of the proximal left anterior descending artery Eur. J. Cardiothorac. Surg., April 1, 2007; 31(4): 691 - 697. [Abstract] [Full Text] [PDF]

				D. M. Holzhey, S. Jacobs, M. Mochalski, T. Walther, H. Thiele, F. W. Mohr, and V. Falk Seven-Year Follow-up After Minimally Invasive Direct Coronary Artery Bypass: Experience With More Than 1300 Patients Ann. Thorac. Surg., January 1, 2007; 83(1): 108 - 114. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Sandra Fraund Georg Lutter Michael Brandt Jochen Cremer Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fraund, S. Articles by Cremer, J. Search for Related Content PubMed PubMed Citation Articles by Fraund, S. Articles by Cremer, J. Related Collections Coronary disease