The German CPU registry: Comparison of smokers and nonsmokers.

BACKGROUND: Chest pain is a major reason for admission to an internal emergency department, and smoking is a well-known risk factor for coronary artery disease (CAD) and acute coronary syndrome (ACS). The aim of this analysis is to illustrate the differences between smokers and nonsmokers presenting to German chest pain units (CPU) in regard to patient characteristics, CAD manifestation, treatment strategy, and prognosis. METHODS: From December 2008 to March 2014, 13,902 patients who had a complete 3­month follow-up were enrolled in the German CPU registry. The analysis comprised 5796 patients with ACS and documented smoking status. RESULTS: Of all the patients in the CPU registry, 35.2% were smokers. Compared with nonsmokers, they were 13.5 years younger (58.2 vs. 71.7 years, p < 0.001), predominantly men (77.1% vs. 65.2%, p < 0.001), and were more frequently diagnosed with single-vessel disease (32.1% vs. 25.2%) as well as ST-elevation myocardial infarction (STEMI; 23.8% vs. 15.5%, p < 0.001). Although the Global Registry of Acute Coronary Events (GRACE) Risk Score for hospital mortality was lower in the group of smokers (106.1 vs. 123.3, p < 0.001), we did not observe any differences in CPU death (0.4% vs. 0.4%, p = 0.69) and CPU major adverse cardiac event (MACE) rates (3.8% vs 2.9%, p = 0.073) between the groups. In the 3­month follow-up, we documented higher mortality rates in the nonsmoker group (1.9% vs. 2.9%, p = 0.035) in correlation with the GRACE Risk Score (80.3 vs. 105.2, p < 0.001). MACE rates were similar during the follow-up (3.1% vs. 4.1%, p = 0.065). CONCLUSION: Observations from the German CPU registry demonstrate that smoking is a strong predictor of acute CAD manifestation early in life, especially STEMI. In spite of a lower GRACE Risk Score and fewer comorbidities, smokers had a rate of hospital mortality similar to the older group of nonsmokers.

Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI) : Joint Consensus Document of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V. (ALKK) and cooperating Cardiac Surgery Departments.

Indications for TF-TAVI (transfemoral transcatheter aortic valve implantation) are rapidly changing according to increasing evidence from randomized controlled trials. Present trials document the non-inferiority or even superiority of TF-TAVI in intermediate-risk patients (STS-Score 4-8%) as well as in low-risk patients (STS-Score < 4%). However, risk scores exhibit limitations and, as a single criterion, are unable to establish an appropriate indication of TF-TAVI vs transapical TAVI vs SAVR (surgical aortic valve replacement). The ESC (European Society of Cardiology)/EACTS (European Association for Cardio-Thoracic Surgery) guidelines 2017 and the German DGK (Deutsche Gesellschaft für Kardiologie)/DGTHG (Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie) commentary 2018 offer a framework for the selection of the best therapeutic method, but the individual decision is left to the discretion of the heart teams. An interdisciplinary TAVI consensus group of interventional cardiologists of the ALKK (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V.) and cardiac surgeons has developed a detailed consensus on the indications for TF-TAVI to provide an up-to-date, evidence-based, comprehensive decision matrix for daily practice. The matrix of indication criteria includes age, risk scores, contraindications against SAVR (e.g., porcelain aorta), cardiovascular criteria pro TAVI, additional criteria pro TAVI (e.g., frailty, comorbidities, organ dysfunction), contraindications against TAVI (e.g., endocarditis) and cardiovascular criteria pro SAVR (e.g., bicuspid valve anatomy). This interdisciplinary consensus may provide orientation to heart teams for individual TAVI-indication decisions. Future adaptations according to evolving medical evidence are to be expected. Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI).

Angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy compared to best medical treatment: One-year interim results of SPACE-2.

BACKGROUND: Treatment of individuals with asymptomatic carotid artery stenosis is still handled controversially. Recommendations for treatment of asymptomatic carotid stenosis with carotid endarterectomy (CEA) are based on trials having recruited patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may lead to a markedly decreasing risk of stroke in asymptomatic carotid stenosis. The aim of the SPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effects of BMT alone with that of BMT in combination with CEA or carotid artery stenting (CAS), respectively, in patients with asymptomatic carotid artery stenosis of ≥70% European Carotid Surgery Trial (ECST) criteria. METHODS: SPACE-2 is a randomized, controlled, multicenter, open study. A major secondary endpoint was the cumulative rate of any stroke (ischemic or hemorrhagic) or death from any cause within 30 days plus an ipsilateral ischemic stroke within one year of follow-up. Safety was assessed as the rate of any stroke and death from any cause within 30 days after CEA or CAS. Protocol changes had to be implemented. The results on the one-year period after treatment are reported. FINDINGS: It was planned to enroll 3550 patients. Due to low recruitment, the enrollment of patients was stopped prematurely after randomization of 513 patients in 36 centers to CEA (n = 203), CAS (n = 197), or BMT (n = 113). The one-year rate of the major secondary endpoint did not significantly differ between groups (CEA 2.5%, CAS 3.0%, BMT 0.9%; p = 0.530) as well as rates of any stroke (CEA 3.9%, CAS 4.1%, BMT 0.9%; p = 0.256) and all-cause mortality (CEA 2.5%, CAS 1.0%, BMT 3.5%; p = 0.304). About half of all strokes occurred in the peri-interventional period. Higher albeit statistically non-significant rates of restenosis occurred in the stenting group (CEA 2.0% vs. CAS 5.6%; p = 0.068) without evidence of increased stroke rates. INTERPRETATION: The low sample size of this prematurely stopped trial of 513 patients implies that its power is not sufficient to show that CEA or CAS is superior to a modern medical therapy (BMT) in the primary prevention of ischemic stroke in patients with an asymptomatic carotid stenosis up to one year after treatment. Also, no evidence for differences in safety between CAS and CEA during the first year after treatment could be derived. Follow-up will be performed up to five years. Data may be used for pooled analysis with ongoing trials.

Admission heart rate in relation to presentation and prognosis in patients with acute myocardial infarction. Treatment regimens in German chest pain units.

BACKGROUND: Higher heart rates on admission have been associated with poor outcomes in patients with an acute coronary syndrome in previous cohorts. Whether such a linear relationship still exists in contemporary high-level care is unclear. METHODS: Prospectively collected data from patients presenting with myocardial infarction (MI) in centers participating in the Chest Pain Unit (CPU) Registry between December 2008 and July 2014 were analyzed. Patients were classified according to their initial heart rate (I: < 50; II: 50-69; III: 70-89; IV: ≥ 90 bpm). A total of 6,168 patients out of 30,339 patients presenting to 38 centers were included in the study. RESULTS: Patients in group IV had more comorbidities, while patients in group I more often had a history of MI. Patients in the lowest heart rate group presented significantly earlier to the hospital (4 h 31 min vs. 7 h 37 min; p < 0.05) and had the highest rate of interventions. The overall survival after 3 months was significantly worse in group IV after adjusting for baseline variables. In the subgroup analysis, heart rate was a prognostic factor in the non-ST-segment elevation MI group but not in the ST-segment elevation MI group. The correlation between heart rate and major adverse cardiac events followed a J-shaped curve with worst outcomes in the lowest and highest heart rate groups. CONCLUSION: Patients admitted to a dedicated CPU with the diagnosis of MI and a heart rate > 90 bpm experience reduced survival at 3 months despite optimal treatment. Patients with bradycardia also seem to be at increased risk for cardiovascular events despite much earlier presentation and treatment.

[Acute jaw-thoracic pain and syncope in a 41-year-old man]. / Akuter Kiefer-Thorax-Schmerz und Synkope bei einem 41-jährigen Patienten.

A 41-year-old physically active man with no significant past medical history presented with sudden thoracic pain. The patient was referred to the next tertiary care hospital. A CT scan showed an ectasia of the ascending aorta with irregularities of the aortic wall without dissection. Despite initial refusal, the patient was referred to a university hospital with experience in aortic surgery. A triphase ECG-synchronized cardiothoracic flash protocol performed on a 256 line CT scanner confirmed an aortic intramural hematoma and a covered aortic perforation. Shortly afterwards the patient collapsed and had to be resuscitated.

Interventional treatment and outcome in elderly patients with stable coronary artery disease. Results from the German ALKK registry.

BACKGROUND: The number of elderly and very elderly patients undergoing percutaneous coronary interventions (PCI) is increasing. We therefore analyzed data from the German ALKK registry (Arbeitsgemeinschaft Leitende Krankenhausärzte; Working Group of Hospital Cardiologists) to determine differences in procedural features, antithrombotic treatment, and in-hospital outcome in patients with coronary artery disease (CAD) according to age in a large series of patients. METHODS AND RESULTS: The present analysis was based on the data of 35,534 consecutive patients undergoing elective PCI who were enrolled in the ALKK registry. Of these 27,145 (76.4 %) were younger than 75 years, 7,645 (21.5 %) were aged between 75 and 84 years, and 744 (2.1 %) patients were older than 85 years. Mean age was 68.5 years (60.9-74.5 years), and 25,784 patients (72.6 %) were male. Overall intraprocedural events were very low (1.1 %) and there was no significant difference between the three age groups [< 75 years (1.1 %); 75-< 85 years (1.2 %); ≥ 85 years (0.5 %) (p = not significant)]. Rates of in-hospital death, stroke and transient ischemic attack (TIA), as well as the combined endpoint in-hospital major adverse cardiac and cerebrovascular events (MACCE) were also very low (0.6 % vs. 0.9 % vs. 0.9 %; p < 0.001) but significantly higher in elderly patients with no further increase in the very elderly patient group. CONCLUSION: We found no differences in this registry in intraprocedural complications during elective PCI between younger and elderly patients. Although in-hospital MACCE were somewhat higher in the elderly, the overall event rate was low and thus elderly patients should not be deprived from this therapy because of age alone.

[Treatment of asymptomatic carotid artery stenosis: improvement of evidence with new SPACE-2 design necessary]. / Therapie asymptomatischer Karotisstenosen: Notwendige Klärung der Evidenz mit neuem SPACE-2-Design.

Asymptomatic carotid artery stenosis may be treated with carotid endarterectomy (CEA), carotid artery stenting (CAS) or with best medical treatment (BMT) only. Definitive and evidence-based treatment recommendations for one of these options are currently not possible. Studies showing an advantage of CEA over BMT alone do not meet current standards from a pharmacological point of view. On the other hand, more recent data point to a further stroke risk reduction using BMT according to current standards. Studies on carotid artery stenting as a third alternative treatment are partially insufficient, especially when comparing CAS with BMT. Initiated in 2009, the randomized, controlled, multicenter SPACE-2 trial is intended to answer the question about the best treatment option of asymptomatic carotid artery stenosis; however, to increase recruitment rates as a condition for the successful completion of this important study, the trial design had to be modified.

[Current guidelines on carotid artery stenting. Critical evaluation]. / Aktuelle Leitlinien zum Karotis-Stenting. Kritische Beurteilung.

Scientific data underlying current guidelines on treatment of carotid artery stenosis is subject to interdisciplinary discussion. In particular selective weighting of the randomized European studies leads to conflicting levels of recommendation and levels of evidence, especially when directly comparing guidelines under surgical versus endovascular guidance. Surgical guidelines recommend a limitation of carotid artery stenting (CAS) to symptomatic patients with specific surgical/anatomical disadvantages and/or severe comorbidities. The European Society of Cardiology (ESC) guidelines recommend the use of CAS only in patients at increased surgical risk but at the same time requires morbidity and mortality rates comparable to those of surgical interventions. Even one step further, the American guidelines and specifically the associated comments of the German Society of Cardiology on the above mentioned ESC guidelines put CAS and carotid endarterectomy (CEA) on a par in terms of treatment alternatives, presupposing analogous CEA complication rates. Differential interpretation of the so far inadequate data is a common issue of current evidence-based medicine. The difficulty in conceptualization of new studies concerning the therapy of carotid stenosis lies in the funding these large projects and also on the high patient number required to achieve adequate statistical power. Furthermore, during the estimated long study period substantial changes of current techniques and devices can be anticipated which might render the study results in part outdated by the time of publication. However, as long as no new randomized study results comparing medical, surgical and interventional treatment of carotid stenosis are available, the question on the optimal therapy for patients with carotid artery disease remains unanswered.

[Carotid artery stenting: is there a volume-outcome correlation?]. / Karotis-PTA: Gibt es einen "Volume-Outcome"-Zusammenhang?

Since carotid artery stenting was introduced into clinical practice as an alternative treatment option for significant carotid artery stenosis, several randomized trials have been published with different minimum requirements for the treating interventionalist and therefore different event rates. Analysis of large single center studies and registries has shown a significant decrease in event rates with an increase in experience in carotid artery stenting techniques. The randomized trials with exactly defined minimum requirements including a reasonable number of prior carotid artery interventions showed comparable results between carotid artery stenting and surgical approaches.

[A young woman with fulminant pulmonary embolism]. / Fulminante Lungenembolie bei einer jungen Frau.

We describe the case of a 24-year-old woman who was admitted to the emergency department with dyspnea and sinus tachycardia. The suspected diagnosis of pulmonary embolism was confirmed by computed tomography (CT) scan. The patient lost consciousness soon afterwards and was found to be pulseless. Cardiopulmonary resuscitation was performed and high dosis thrombolysis was given. The patient survived without sequelae and was discharged on oral anticoagulation from the hospital 8 days after the initial admission. In our opinion unknown factor-V Leiden in combination with a local form of hormonal contraception (NuvaRing®) was responsible for the deep venous thrombosis of the left leg and the pulmonary embolism.

Age-related differences in diagnosis, treatment and outcome of acute coronary syndromes: results from the German ALKK registry.

AIMS: The elderly constitute an increasing proportion of all patients with acute coronary syndromes (ACS). However, increased age has been identified as an important risk factor for adverse events and complications of ACS and treatment. The purpose of this study was to investigate age-related differences in presentation and diagnostics, as well as contemporary treatment and outcome in a large series of elderly patients receiving an invasive strategy for ACS. METHODS AND RESULTS: The present study is an analysis of all patients, who were enrolled in the German Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK) registry in 2008. To assess age-related differences, subjects were divided into three groups: (<75 yrs, 75 to 85 yrs and >85 yrs). Out of 19,708 consecutive patients who were admitted for the treatment of ACS and enrolled in the ALKK registry, 14,174 (71.9%) were <75 yrs, 4,685 (23.8%) were between 75 and 84 yrs and 849 (4.3%) patients were >85 yrs. Therapy recommendation after diagnostic angiography was conservative in 24.6% of the youngest, in 25.1% of the elderly, and in 25.3% of the very elderly patients. Interventional success rates were 95.2% in the youngest vs. 93.1% in the elderly and very elderly patient group (p<0.001). Overall in-hospital event rate increased significantly with age (3.4% vs. 7.4% vs. 8.3%, respectively; p<0.001). CONCLUSIONS: Our analysis shows that there is a high success rate among the large proportion of elderly patients who are treated for ACS by an intervention. Complication rates increased significantly, however, with age.

Stent-protected angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy: SPACE2 - a three-arm randomised-controlled clinical trial.

Moderate to severe (> or =70%) asymptomatic stenosis of the extracranial carotid artery leads to an increased rate of stroke of approximately 11% in 5 years. Patients with asymptomatic carotid stenosis, however, are also at a higher risk of nonstroke vascular events. The estimated annual risks of such events in patients with asymptomatic stenosis are 7% for a coronary ischaemic event and 4-7% for overall mortality. The superiority of carotid endarterectomy compared with medical treatment in symptomatic carotid disease is established, provided that the surgical procedure can be performed with a perioperative morbidity and mortality of <6%. The advantage of carotid endarterectomy for asymptomatic patients is less established. An alternative treatment, carotid artery stenting, has been developed. This treatment is used frequently in both symptomatic and asymptomatic patients. In the last decade, major advantages in medical primary prevention of cerebrovascular and cardiovascular disease have been accomplished. The control groups in the large trials for asymptomatic carotid artery disease (ACAS and ACST) originate from more than a decade ago and, for the most part, have not received a medical primary prevention strategy that would now be considered the standard according to current national and international guidelines. For this reason, a three-arm trial (SPACE2; http://www.space-2.de) with a hierarchical design and a recruitment target of 3640 patients is chosen. Firstly, a superior trial of intervention (carotid artery stenting or carotid endarterectomy) vs. state-of-the-art conservative treatment is designed. In case of superiority of the interventions, a noninferiority end-point will be tested between carotid artery stenting and carotid endarterectomy. This trial is registered at Current Controlled Trials ISRCTN 78592017.

Glycoprotein IIb/IIIa antagonists during carotid artery stenting: results from the carotid artery stenting (CAS) registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK).

BACKGROUND: Glycoprotein II b/IIIa antagonists (GPII b/IIIa-A) lower the periprocedural rate of ischemic events during high risk percutaneous coronary interventions. Their clinical impact on carotid artery stenting (CAS) remains to be determined. METHODS: We analyzed data from the Carotid Artery Stent (CAS) Registry. RESULTS: From 01/ 2000 to 06/2005 1322 CAS interventions were registered. In 94 (7.1%) procedures a GPII b/IIIa-A was used: abciximab in 8 cases (8.6%), tirofiban in 53 cases (57%) and eptifibatide in 32 cases (34.4%). The use of a GPII b/IIIa-A during CAS decreased significantly over time: from 17.6% in 2000 to 3% in 2005, p for trend <0.0001. The mean use of a GPII b/IIIa-A at the hospitals was 5.2%. More than 50% of the hospitals never used a GPII b/IIIa-A. There were no significant differences in baseline characteristics and concomitant diseases in CAS patients treated with GPII b/IIIa-A compared to those without GPII b/IIIa-A. A bilateral intervention was performed more often in patients treated with GPII b/IIIa-A (2.1 vs 0.2%, p = 0.04), a thrombus was more often visible (27 vs 12.4%, p <0.001) and an ulcer more frequently diagnosed (50 vs 37.5%, p = 0.03). There was no significant difference in the combined death or stroke rate between the two groups (5.3 vs 3.0%, p = 0.22, OR = 1.81, 95% CI: 0.69-4.72), which was confirmed by logistic regression analysis after adjusting for possible confounders (OR = 1.67, 95% CI: 0.62-4.46, p = 0.31). CONCLUSIONS: Our data neither demonstrate a significant benefit nor a significant risk with the use of GPIIb/IIIa-A during CAS. However, only an adequately sized randomized controlled clinical trial could establish the real value of GPII b/IIIa-A during CAS. Until then, considering the potential increase in cerebral hemorrhage, we should not use GPII b/ IIIa-A routinely during CAS.

First in-human randomized comparison of an anodized niobium stent versus a standard stainless steel stent--an intravascular ultrasound and angiographic two-center study: the VELA study.

OBJECTIVES: The purpose of this study was to test the hypothesis that a niobium stent might lower the restenosis rate in de novo coronary lesions as compared to a bare metal stent. BACKGROUND: Recent data have suggested that inflammatory and allergic reactions to certain compounds in metal stents may play a role in the onset of restenosis. Thus, niobium as an inert material might be beneficial in lowering the rate of restenosis. METHODS: In this single blind, two-center prospective trial patients were randomized into two groups; the first group (n=32) received a niobium stent (VELA STF), the second group (n=33) a bare metal stent (Antares STF). Clinical follow-up was performed at 1 and 6 months, angiographic and intravascular ultrasound analyses were performed at the 6-month follow-up. RESULTS: All stents were successfully deployed. There was one stent thrombosis in each group. There were no significant differences concerning minimal lumen diameter, percent stenosis, and late lumen loss as assessed by intravascular ultrasound (IVUS) at the 6- month follow-up. At 30 days and at 6 months, there were no differences observed between the two groups regarding the rate of major cardiac adverse events. Immediately after stent implantation minimal lumen diameter was significantly larger (p=0.01) and residual percent stenosis significantly lower (p=0.01) in the niobium stent group. CONCLUSION: The use of a niobium stent showed comparable results with other non-drug-eluting stents; however the inert qualities of this first generation niobium stent did not translate into a mid- or long-term benefit.

[Interventional treatment of extracranial carotid stenoses: current status, requirements and indications]. / Positionspapier zur Indikation und Durchführung der interventionellen Behandlung extrakranieller Karotisstenosen.

Interventional treatment of extracranial carotid stenoses: current status, requirements and indications Around 30000 strokes per year in Germany are caused by extracranial obstructions of the carotid arteries. Besides the well established surgical endatherectomy, which has been proven to be superior to medical treatment alone in randomized multicenter trials, percutaneous treatment by balloon angioplasty and stent placement is increasingly performed. This consensus paper summarizes the present status of scientific studies and controlled treatment registries of carotid angioplasty and stenting and yields to recommendations regarding its performance and indication. A Medline search was done until August 2005 including all randomized comparative studies with clinical endpoints and all controlled registries with more than 500 patients included. Both completed randomized trials comparing angioplasty and stenting with surgery (CAVATAS and SAPPHIRE) did not show a significant difference with respect to stroke and death within 30 days. The incidence of this combined endpoint was between 3.3 and 6.9% in large multicenter registries. Thus, the current endovascular treatment results in a perlinterventional complication rate comparable to that which is commonly accepted for vascular surgery. A systematic preferably external quality monitoring as well as interdisciplinary cooperation most importantly with neurologists is recomendedfor all interventionalists. Based on available clinical data, this consensus paper defines recommendation classes I or II with a level of evidence B or C depending on symptoms, operative risk status of the patient and severity of the underlying stenosis.

Recurrent tako-tsubo-like left ventricular dysfunction (apical ballooning) in a patient with pheochromocytoma - a case report.

Primarily described in Japan, tako-tsubo-like left ventricular dysfunction is a phenomenon characterized by transient apical ballooning in the absence of significant coronary artery disease. The clinical presentation includes symptoms like chest pain, dyspnea, syncope, electrocardiographic changes and elevated myocardial markers, all compatible with the diagnosis of an acute coronary syndrome. The underlying mechanism is supposed to be a catecholamine excess caused by various triggers. We describe a patient with a recurrent tako-tsubo phenomenon, who at work-up proved to have a pheochromocytoma as the most likely underlying disease.