Clinical Research in Cardiology

, Volume 101, Issue 11, pp 929–937

The role of endovascular expertise in carotid artery stenting: results from the ALKK-CAS-Registry in 5,535 patients

  • Stephan Staubach
  • Ralph Hein-Rothweiler
  • Matthias Hochadel
  • Manuela Segerer
  • Ralf Zahn
  • Jens Jung
  • Gotthard Rieß
  • Hubert Seggewiß
  • Andre Schneider
  • Thomas Fürste
  • Christian Gottkehaskamp
  • Harald Mudra
Original Paper

DOI: 10.1007/s00392-012-0479-4

Cite this article as:
Staubach, S., Hein-Rothweiler, R., Hochadel, M. et al. Clin Res Cardiol (2012) 101: 929. doi:10.1007/s00392-012-0479-4

Abstract

Purpose

Several scientific committees have proposed an accentuation of operator minimal requirements before accreditation for carotid artery stenting is granted. The current study aims to identify potential effects from increasing site experience on periprocedural safety and outcome of carotid artery stenting (CAS).

Methods

Between 1996 and December 2009, 5,535 procedures have been entered into the prospective, controlled ALKK-CAS-Registry. The total cohort was divided in four subgroups according to the consecutive patient order at each participating center: patients 1–49 (n = 1,485), 50–99 (n = 1,118), 100–199 (n = 1,521) and ≥200 (n = 1,411).

Results

The median age of all patients was 71 years; 52.8 % had a symptomatic carotid stenosis. A decline in the rates of in-hospital major stroke (2.1, 1.9, 1.6, 0.9, p for trend 0.014) and of ipsilateral strokes (3.1, 2.4, 2.5, 1.6 %, p for trend 0.019) was substantiated with increasing site experience. This significant trend was preserved in the combined rate of major stroke and death (4.0, 3.2, 3.4, 2.4 %, p for trend 0.034).

Apart from CAS experience, improvements in CAS technique, a decreasing number of symptomatic patients and an increasing number of procedures under embolic protection (each p for trend <0.05) might have contributed to these results.

Conclusions

The results show a gradual reduction of in-hospital stroke rates with increasing center experience. Extensive supervision of CAS learners and further promotion of proctorship programs seem to be essential.

Keywords

Carotid artery stenosis Cartotid artery stenting Death or stroke Learning curve Center experience 

Introduction

Since the publication of several randomized trials comparing CAS with carotid endarterectomy (CEA), an outstanding discussion was provoked. Currently, there is controversy about the requirements of the operator performing CAS within and beyond randomized trials.

Since the first introduction of carotid artery stenting (CAS) into clinical practice [1], a remarkable decrease of procedure-related complications was achieved for de novo lesions [2, 3] and repeat carotid interventions [4] in the last few years. Recent data have shown that patient characteristics such as comorbidities, age and symptomatology of carotid stenosis, preprocedural medication and history of smoking have an impact on outcome [5, 6, 7, 8]. In the past, several study protocols of large randomized trials comparing CAS with carotid endarterectomy, proposed a broad range of requirements on the operator: for example, in ICSS those with merely ten CAS procedures were allowed to take part in the study [9], while other studies performed a continuous training and lead-in phase to exclude inexperienced investigators [10].

Therefore, several scientific committees [11, 12] and study investigators [10] have proposed an accentuation of operator minimal requirements. It has been shown that little experience and hospital volume of CAS are associated with more procedural complications and worse outcomes [7, 13]. The investigators of a prospective study (CAPTURE-2) revealed both site and operator CAS volume as one of the most important determinants that influenced CAS outcome [13]. Accordingly, the purpose of the present study was to identify the effects of increasing operator experience on periprocedural safety and outcome of carotid artery stenting (CAS) in a large unselected cohort of patients treated within a prospective registry.

Methods

The German CAS Registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK) is an ongoing registry that was initiated in 1996 to document the current indications and outcomes of CAS and to improve its quality. Every patient treated by percutaneous intervention was prospectively enrolled in the registry. Furthermore, all in-hospital complications were prospectively documented. For the present report, we analyzed 5,535 patients treated from 1996 to December 2009. The details of the registry have been described elsewhere [14, 15].

Patients were divided into four groups according to the chronological order they were treated at each center. Every patient numbered 1–49 at each participating center was pooled in group 1 (in total n = 1,485), those with chronological number 50–99 in group 2 (in total n = 1,118), those with number 100–199 in group 3 (in total n = 1,521) and those with number 200 and plus in group 4 (in total n = 1,411). For each patient, the first procedure performed or attempted during the hospital stay was analyzed.

Statistics

Categorical variables are reported as percentages and continuous variables as the median and interquartile range. To demonstrate trends across the four groups, two-sided Cochran–Armitage test or Jonckheere–Terpstra test was used, as appropriate.

Logistic regression models were used to analyze the association of the center experience with in-hospital outcome controlling for other temporal trends, notably the increasing use of protection devices and the decreasing proportion of symptomatic patients (Tables 1 and 3). Two in-hospital end points were regarded, namely death or stroke and death or cerebral ischemic event, defined as major, minor stroke, TIA and amaurosis fugax. The patient number was included in the mentioned categorized form as well as linearly. Further baseline characteristics that exhibited a significant trend in Table 2 were tentatively added to these models one at a time, but did not achieve statistical significance and were therefore not included.
Table 1

Lesions and interventional characteristics

Variable

Group 1

(1–49)

Group 2

(50–99)

Group 3

(100–199)

Group 4

(200+)

p valuea

Number of patients

1,485 (26.8 %)

1,118 (20.2 %)

1,521 (27.5 %)

1,411 (25.5 %)

 

Lesion characteristics

     

 Ulcer (%)

22.7

23.7

18.5

23.2

0.420

 Thrombus (%)

7.3

5.1

6.1

7.0

0.921

 Severe calcification (%)

22.0

25.1

23.4

23.6

0.464

 Length >10 mm (%)

35.6

37.3

34.2

33.4

0.100

 Bifurcation (%)

30.6

29.0

25.4

20.3

<0.001

Performed procedures

1,450 (27 %)

1,082 (20.1 %)

1,484 (27.6 %)

1,361 (25.3 %)

<0.001

Stent implantation (%)

97.8

97.7

97.8

98.2

0.496

Protection device (%)

61.4

78.5

90.0

94.5

<0.001

 Filter (%)

85.6

92.2

92.7

98.0

<0.001

 Distal occlusion (%)

12.4

5.4

4.9

1.0

<0.001

 Proximal occlusion (%)

2.0

2.4

2.3

0.9

0.061

 Predilatation (%)

22.9

14.0

6.2

6.9

<0.001

aCochran–Armitage test

Table 2

Patient characteristics

Variable

Group 1

(1–49)

Group 2

(50–99)

Group 3

(100–199)

Group 4

(200+)

p valuea

Number of patients

1,485 (26.8 %)

1,118 (20.2 %)

1,521 (27.5 %)

1,411 (25.5 %)

 

Age (years)

    

0.464b

 Median

71

71

71

71

 

 Interquartile range

65–77

65–77

65–77

65–77

 

Age ≥75 years (%)

34.7

32.5

36.1

35.4

0.353

Male (%)

72

71.9

71.5

72.4

0.867

CHD (%)

70.1

64.8

64.1

64.7

0.002

MI (%)

29.4

27.3

25.1

24.5

0.001

PCI/CABG (%)

45.1

40.8

42.4

37.1

0.009

PAD (%)

24.9

28.6

23.5

26.0

0.853

Hypertension (%)

91.4

91.6

90.8

93.5

0.098

Hypercholesterinemia (%)

78.7

81.0

83.0

89.4

<0.001

Heart failure (%)

7.9

8.2

6.6

7.8

0.679

Atrial fibrillation (%)

12.2

10.2

9.5

8.3

0.002

Diabetes mellitus (%)

34.3

37.3

31.3

36.1

0.976

Renal failure (%)

20.6

19.1

18.0

15.3

0.012

Severe COPD (%)

4.7

4.4

5.3

4.1

0.636

Smokers (%)

24.2

28.4

26.4

32.8

<0.001

aCochran–Armitage test, unless otherwise indicated

bJonckheere–Terpstra test

The tests were performed using the Statistical Analysis Systems statistical package, version 9.2 (SAS Institute, Cary, NC, USA). p values ≤0.05 were considered to be statistically significant.

Results

From 1996 to December 2009, 5,535 patients were admitted for CAS procedures, performed at 36 participating centers. More than 70 % of the patients were male. The median age was 71 years; 52.8 % of the patients had a symptomatic carotid stenosis. Among the four groups, there were significant differences in baseline characteristics regarding coronary artery disease, prior myocardial infarction, hypercholesterolemia, history of smoking, atrial fibrillation and renal failure (Table 2).

The first patients treated with CAS were more frequently symptomatic and not so often treated preoperatively. The use of clopidogrel, β-blockers and statins was lower (Table 3).
Table 3

Symptoms/history regarding CAS

Variable

Group 1

(1–49)

Group 2

(50–99)

Group 3

(100–199)

Group 4

(200+)

p valuea

Number of patients

1,485 (26.8 %)

1,118 (20.2 %)

1,521 (27.5 %)

1,411 (25.5 %)

 

Symptomatic CAS (%)

64.1

55.9

49.1

44.0

<0.001

 Recurrent (%)

24.6

22.6

27.0

27.7

0.510

Asymptomatic (%)

35.9

44.1

50.9

56.0

<0.001

 Preoperative state (%)

18.6

19.4

17.8

14.1

0.021

Ipsilateral/bilateral symptomatic (%)

54.7

44.6

39.7

36.9

<0.001

 Major stroke (%)

26.4

30.6

23.0

23.0

0.053

 Minor stroke (%)

14.7

17.4

17.0

19.4

0.055

 TIA (%)

50.4

42.2

48.2

36.5

<0.001

Contralateral symptomatic (%)

6.1

7.0

6.3

3.5

0.004

Prior CEA (%)

8.3

7.7

6.1

7.8

0.307

Prior CAS (%)

5.2

8.0

8.2

9.6

<0.001

Chronic pre-medication

     

 Aspirin (%)

81.9

88.2

90.4

91.3

<0.001

 Clopidogrel (%)

50.1

53.8

67.7

74.1

<0.001

 Warfarin (%)

6.5

5.2

6.8

4.7

0.277

 ACE-/AT-1-inhibitor (%)

72.4

71.8

76.0

70.6

0.555

 β-Blocker (%)

53.8

61.3

60.8

64.6

<0.001

 CCB (%)

20.9

19.2

19.7

14.8

0.005

 Statin (%)

74.7

71.6

74.3

81.1

<0.001

aCochran–Armitage test

In-hospital outcome (Table 4)

A decline in the rates of in-hospital major stroke (2.1 % in group 1, 1.9 % in group 2, 1.6 % in group 3 and 0.9 % in group 4, p for trend 0.014) and in the total number of ipsilateral strokes (3.1, 2.4, 2.5 and 1.6 %, p for trend 0.019) paralleled with increasing center experience (Fig. 1). This significant trend persisted after combining the rates of major stroke and death (4.0, 3.2, 3.4 and 2.4 %, p for trend 0.034).
Table 4

In-hospital outcome

 

(1–49)

(50–99)

(100–199)

(200+)

p valuea

Number of patients

1,485 (26.8 %)

1,118 (20.2 %)

1,521 (27.5 %)

1,411 (25.5 %)

 

Death (%)

0.4

0.5

0.5

0.7

0.324

Major stroke (%)

2.1

1.9

1.6

0.9

0.014

Minor stroke (%)

1.7

1.3

1.5

1.0

0.141

TIA (%)

3.8

3.0

2.9

2.0

0.005

Death or stroke (%)

4.0

3.2

3.4

2.4

0.034

Death or cerebral ischemia (%)

7.9

6.5

6.5

4.4

<0.001

Death or major stroke ipsilateral (%)

1.9

1.7

1.4

1.2

0.118

Ipsilateral ischemic event (%)

6.5

5.0

5.3

3.1

<0.001

Stroke ipsilateral (%)

3.1

2.4

2.5

1.6

0.019

TIA ipsilateral (%)

3.2

2.4

2.5

1.6

0.012

Contralateral ischemic event (%)

1.2

1.1

1.0

0.7

0.123

Myocardial infarction (%)

0.1

0.0

0.0

0.1

0.992

aCochran–Armitage test

Fig. 1

In-hospital complications: death or stroke rate and major stroke rate (p for trend <0.05). The patients of each center have been registered chronologically in the ALKK registry. For this analysis, patients were divided into four groups according to the chronological order in which the patient was treated at each center. Patients no. 1–49 at each participating center was pooled into group 1 (in total n = 1,485), patients with chronological number 50–99 in group 2 (in total n = 1,118), those with number 100–199 in group 3 (in total n = 1,521) and those with number 200 and plus in group 4 (in total n = 1,411). Pts patients

Logistic regression

The use of embolic protection devices during CAS has increased over the years (Table 1). In detail, 61.4 % of procedures in group 1, 78.5 % in group 2, 90 % in group 3 and 94.5 % in group 4 were done under embolic protection (p for trend <0.001).

In the logistic regression analysis (Tables 5, 6), the number of performed procedures was not a significant predictor for the end point of death or stroke (Table 5a, b). However, protection devices and symptomatic patients had a significant influence on the end point death or stroke (Table 5a, b). This is true for the categorized model with the arbitrary cut points (nos. 1–49, 50–99, 100–199, 200+) as well as for the procedure count per center linearly. In contrast, the number of performed procedures or in other words institutional experience predicted a better outcome in the categorized model with arbitrary cut points, as well as in the procedure count per center linearly regarding death or cerebral ischemic event (Table 6b). However, the use of a protection device system remained the strongest predictor throughout (p < 0.01).
Table 5

OR regarding the end point death or stroke

Variable

Odds Ratio

95 % confidence limits

p value

(a)

 50–99 versus 1–49

0.89

0.56–1.42

0.537

 100–199 versus 1–49

1.07

0.70–1.65

 200+ versus 1–49

0.77

0.48–1.25

 Protection device

0.51

0.35–0.75

<0.001

 Symptomatic Patients

1.56

1.10–2.22

0.012

(b)

 Number of procedures (per increase of 10)

0.991

0.977–1.006

0.220

 Protection device

0.53

0.36–0.78

0.001

 Symptomatic Patients

1.55

1.09–2.19

0.014

OR regarding the end point death or stroke. Patients were divided into groups 1–4 (1–49, 50–99, 100–199, 200+). (a) includes the arbitrary cut points; (b) includes the linear procedure count

Table 6

OR regarding the end point death or cerebral ischemic event

Variable

Odds ratio

95 % confidence limits

p value

(a)

 50–99 versus 1–49

0.80

0.57–1.12

0.049

 100–199 versus 1–49

0.91

0.67–1.24

 200+ versus 1–49

0.62

0.46–0.88

 Protection device

0.62

0.46–0.84

0.002

 Symptomatic Patients

1.47

1.15–1.89

0.002

(b)

 Number of procedures (per increase of 10)

0.984

0.974–0.995

0.005

 Protection device

0.64

0.48–0.86

0.003

 Symptomatic Patients

1.46

1.13–1.87

0.003

OR regarding the end point death or cerebral ischemic event. Patients were divided into groups 1–4 (1–49, 50–99, 100–199, 200+). (a) includes the arbitrary cut points; (b) includes the linear procedure count

Furthermore, with an increasing number of interventions per center, the rate of patients with relevant comorbidities, e.g., coronary heart disease, myocardial infarction, prior coronary intervention and renal failure, decreased (Tables 2, 3), yet patients showed a significant trend to an increased cardiovascular risk profile (smoking, hypercholesterinemia). Finally, these baseline characteristics had no significant influence on the outcome after adjustment.

Additionally, predilation was performed less frequently before placing the embolic protection device, as well as treatment of bifurcations (Table 1) with an increasing number of patients. However, these variables did not significantly impact outcome.

Discussion

In our study, we investigated the influence of the experience of the site on the outcome during CAS in a large number of prospectively enrolled patients. Our results show that with an increasing number of interventions, the complication rate could be decreased significantly. The end point of death or stroke decreased from 4 % in the first 50 patients to 2.4 % in >200 treated patients, and in-hospital rates for all major strokes and ipsilateral strokes were decreased with increase in site experience.

Besides patient selection, the effect of the learning curve that is related to the experience of the investigator strongly influences the results of CAS [7, 13]. Comparing CAS with other endovascular invasive procedures, CAS is associated with a devastating potential of complications, primarily embolic strokes. Furthermore, CAS represents a more challenging endovascular procedure, especially with the use of an embolic protection device.

The question how many procedures qualify to be a participant at a randomized study or even to perform CAS beyond a supervised trial is not well studied yet.

In Europe, a cooperative multisociety document from neuroradiologists, vascular and endovascular surgeons, and interventional cardiologists and radiologists sets the minimum standards to perform carotid artery stenting. At least 150 supraaortic vessel angiographies, >100 as a primary operator with at least 75 CAS procedures and >50 of them as the primary operator, had to be performed. Furthermore, to maintain competence, >50 CAS procedures had to be performed annually further on [16].

In a large, prospective multicenter registry, investigating possible parameters for peri-interventional stroke or death, center experience was found to be a significant predictor. Patients were divided into three groups according to their chronological number they were treated (≤50 vs. 51–150 vs. ≥151 interventions) [7].

Further reports agreed that operators’ expertise was an important factor for technical and clinical success of the CAS procedure. In a study with a series of 200 CAS procedures, a significant difference could be seen between the first and last 50 patients regarding stroke or death rate [17]. Other, also smaller reports showed similar results after CAS [18, 19].

Recent data from the clinical CAPTURE 2 study confirmed the significance of both site and operator CAS volume as the most important determinants. A regression model revealed a minimum case number of 72 CAS procedures per operator to achieve a death/stroke rate of <3 % [13].

To interpret the results of the recent randomized trials comparing CAS versus CEA adequately, the requirements for the investigator to take part in the trials have to be considered precisely. Table 7 summarizes the requirements for each operator to be allowed to participate in those studies. As a consequence, patients allocated to stenting in recent European randomized trials might have been exposed to an unnecessary risk due to the acceptance of also less experienced investigators [9, 20, 21].
Table 7

Requirements of interventional expertise in large randomized trials comparing CEA with CAS

Study

N (total)

Years

S/A

EPD (%)

Endovascular expertise

CAVATAS [42]

504

2001

+/+

Training in neurology and angioplasty, not necessarily in carotid stenosis. Tutor assistance allowed

SAPPHIRE [32]

334

2004

+/+

96

Periprocedural death or stroke rate had to be <6 %, tutor assistance not allowed

SPACE [21]

1,200

2006

+/−

27

Ten successful CAS procedures or assistance

EVA-3S [20]

527

2006

+/−

78–98

At least 12 CAS or at least 35 stenting procedures in the supraaortic trunks, of which at least 5 were in the carotid artery. Tutor assistance allowed

ICSS [9]

1,710

2010

+/−

72

A total of 50 stenting procedures, at least 10 CAS. Tutor assistance allowed

CREST [22]

2,502

2010

+/+

96

Continuous training and lead-in phase, exclusion of 50 % of the attendees

N number of patients, S/A symptomatic/asymptomatic carotid artery stenosis, EPD embolic protection device

For CREST, 12 CAS procedures had to be done annually with a complication rate <3 % in asymptomatic and <6 % in symptomatic patients. On the other hand, to be a participant in EVA-3S, 12 CAS procedures, performed at any time, or even 5 CAS procedures, if 30 supraaortic procedures were done in the past, were sufficient [20].

The low complication rate of CREST, which was comparable to CEA, most likely is based on a structured training and credentialing of carotid artery stenting operators. Of 427 appliers, half of them were excluded after training and were performing a “lead-in” period. Not surprisingly, interventionalists, who had performed less than 15 procedures compared to those with more procedures, had a higher death or stroke rate (7.1 vs. 3.7 %) [22].

Use of embolic protection devices (EPD) and influence on the learning curve

In our study, the use of a protection device and asymptomatic patients correlated with a lower death or stroke and death or cerebral ischemic event rate. The experience of the institution was not a significant predictor regarding the end point of death or stroke. However, it significantly decreased the death or cerebral ischemic event rate, including also transient ischemic attacks and amaurosis fugax.

Furthermore, logistic regression analysis revealed the use of a protection device as the strongest predictor regarding the end point as stated below. The use of a protection device system during CAS to mitigate risks associated with release of embolic material from carotid lesions into the neurovasculature has been widely accepted [23, 24], although not without controversy because, up to now, no convincing randomized study to specifically assess the impact of EPDs exists [23, 25, 26, 27, 28].

Two small randomized studies comparing CAS procedures with and without embolic protection systems failed to prove a benefit in MRI surrogate parameters and in clinical outcome, respectively [27, 29].

A large review of 2009 including 12,263 protected versus 11,198 unprotected CAS patients revealed that the use of a protection decreased the periprocedural risk for strokes. The relative risk for stroke was 0.62 in favor for those treated with an embolic protection device [30]. A previous international survey of 12,392 CAS procedures reported a death and stroke rate of 2.8 % using a protection device, compared to 6.2 % [31]. A comparably low stroke rate for CAS was found when embolic protection devices were used in experienced hands within the CREST and SAPPHIRE studies after a strict credentialing of the operators during a lead-in phase [22, 32].

Interestingly, the safety committee of the EVA-3S trial recommended stopping the performance of CAS without any use of a protection system, because the 30-day rate of stroke was 26.7 %, 3.9 times higher compared to the procedures using a protection device [20]. By mandating that, however, several users might have been forced to use such a device without sufficient training, which could be one reason for the comparably high event rate in this trial [33, 34, 35].

In real-life practice as seen in a couple of registries, the use of a protection device system is appreciated by experienced CAS operators with good clinical results [24, 36, 37, 38, 39, 40].

In the EMPIRE trial including symptomatic and asymptomatic patients, using the GORE flow reversal system, the stroke and death rate was 2.9 %, among the lowest in CAS trials so far [41].

In summary, besides the symptomatic status of the patients, the operators’ experience and even more pronounced the use of an embolic protection device had a significant impact on the rate of death or stroke after CAS. However, the use of embolic protection devices by itself enhances the need of training and routine of the operator. These correlations support the value of high-volume centers with long experience and continuous performance of CAS procedures.

Limitations of the study

There are some limitations of this study. Since the CAS Registry is an observational albeit prospective study, it is not possible to control the selection of the patients. Therefore, a positive selection bias cannot be absolutely ruled out in this registry. Nevertheless, we believe that our registry due to the large number of real-world data in “all-comers” represents a solid basis for analysis. Additionally, a neurologist, before discharge from the hospital, examined 66 % of the first 50 patients. In group 4 (>200 patients), it decreased to 58 %. Therefore, the diagnosis, especially of minor ischemic events, might have been underestimated.

A further limitation is the lack of information on the exact number of operators at each of the 36 sites participating in this study. Hence, we were not able to analyze and calculate the complication rate at the operator level. However, in the high-volume centers of the registry accounting for around 300–500 patients, respectively, only one operator or one further proctored and supervised operator performed the procedures. Finally, we included only periprocedural data until hospital discharge. It may be difficult to compare our data to 30-day follow-up outcome of other studies.

Conclusions

In the present prospective registry, the complication rate during CAS decreases with institutional experience. Our study showed a substantially lower incidence of stroke and death in patients treated in high-volume centers. A more intense training of operators seems mandatory to optimize the outcome after CAS. A positive learning curve with consequently fewer complications will contribute to further improvement of CAS in selected patients. The use of embolic protection seems to contribute substantially to a lower complication rate on the one hand, but underscores the need of specific training on the other.

Conflict of interest

The authors declare that they have no conflict of interest.

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Stephan Staubach
    • 1
  • Ralph Hein-Rothweiler
    • 1
  • Matthias Hochadel
    • 2
  • Manuela Segerer
    • 1
  • Ralf Zahn
    • 3
  • Jens Jung
    • 4
  • Gotthard Rieß
    • 5
  • Hubert Seggewiß
    • 6
  • Andre Schneider
    • 7
  • Thomas Fürste
    • 8
  • Christian Gottkehaskamp
    • 9
  • Harald Mudra
    • 1
  1. 1.Klinik für Kardiologie, Pneumologie und Internistische IntensivmedizinKlinikum NeuperlachMunichGermany
  2. 2.Stiftung Institut für Herzinfarktforschung an der Universität HeidelbergLudwigshafenGermany
  3. 3.Herzzentrum LudwigshafenLudwigshafenGermany
  4. 4.Medizinische Klinik I, Klinikum WormsWormsGermany
  5. 5.Klinik für Kardiologie und Internistische IntensivmedizinKlinikum BogenhausenMunichGermany
  6. 6.Kardiologie, Nephrologie, Pulmologie, Interventionelle Angiologie, Internistische IntensivmedizinLeopoldina KrankenhausSchweinfurtGermany
  7. 7.Klinik für Kardiologie, Angiologie, PneumologieKlinikum EsslingenEsslingenGermany
  8. 8.Kardiologie und AngiologieKlinikum SiloahHannoverGermany
  9. 9.Klinik für Innere Medizin und KardiologieMarienhospital OsnabrückOsnabrückGermany

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