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).

[Certification in cardiology : Contra: The concept should be improved]. / Zertifizierungen in der Kardiologie : Kontra: Das Konzept sollte verbessert werden.

Increasing complexity and new highly differentiated therapeutic procedures in cardiology result in a need for additional training beyond cardiology board certification. The German Cardiac Society therefore developed a variety of certifications of educational curricula and definition of specialized centers. Standardization and structuring in education and patient treatment, as defined by certifications may be helpful; however, introduction of certification can have serious consequences for hospital structure, the side effects of which may impair quality of treatment for individual patients. The current article discusses these issues against the background of the following questions: how is quality defined? How do certifications interfere with patient care on a nationwide level, how do they influence responsibilities and teamwork? Are there conflicts of interests by designing certifications and how good are the organizational structures? Finally, suggestions are made on what has to be considered when designing certifications. Certifications should acknowledge all cardiologists, irrespective of their position in the level of care. There should be a coherent unified concept synchronizing all certifications and administration needs to be transparent and well structured.

Occurrence of acute myocardial infarction in winter tourists: data from a retrospective questionnaire.

BACKGROUND: Every year millions of tourists spend their vacation in Tyrol, Austria during the winter season. They often perform sports at high altitudes and at low temperatures, factors that might cause acute myocardial infarction (AMI). This study aimed to evaluate the relationship of first physical activity and the onset of AMI in winter tourists. METHODS: We carried out a retrospective analysis of consecutive patients admitted to the Department of Internal Medicine III at the Medical University of Innsbruck with the diagnosis of an AMI between 2006 and 2010. We identified 172 patients as potential candidates for the questionnaire. We successfully contacted 110 patients (mean age: 60 ± 10 years). The location of visit, duration of stay, time of arrival, first sportive activity and onset of symptoms were assessed. RESULTS: During the first 2 days of physical activity , 56% of AMIs occurred. In tourists who suffered AMI during, or within 1 h after cessation of activity (52%), the mean time from the start of the activity to the onset of symptoms was 2.0 ± 1.7 h. 56% of patients performed less than 2.5 h of sport per week before their vacation and 70% had ≥2 cardiovascular risk factors. Although the mean planned vacation time was 8.3 ± 3.7 days, 39% of the patients suffered from AMI on the day of arrival or the day after. CONCLUSION: The majority of AMIs in winter tourists happens within the first 2 days after arrival and within the first 2 days of physical activity.

[Care of patients after coronary stent implantation: what is important in practice?]. / Betreuung von Patienten nach Koronarstentimplantation : Was ist wichtig für die Praxis.

The introduction of Drug Eluting Stents was an important step to reduce restenosis rate after coronary stent implantation. Unfortunately, reduction of restenosis was paid off by the price of potential increased late (>30 days) stent thrombosis. However, current data are not completely conclusive with respect to extent and duration of stent thrombosis and cardiovascular risk after drug eluting stent implantation. Until now, especially for patients at risk for stent thrombosis a prolonged (12 instead of 6 months) dual antiplatelet therapy with aspirin and clopidogrel is recommended. Thereby, the quality of physician instructions is predictive for patient's compliance. Premature termination of dual antiplatelet therapy should be avoided; many small surgical interventions (e.g. tooth extraction) can be performed under dual antiplatelet therapy. Patients with "triple therapy" (aspirin, clopidogrel and coumarin derivate) should be monitored carefully, since they have an excessive bleeding risk. An elective coronary angiography after coronary stent implantation is not routinely necessary. However in selected high-risk patients (e.g. left main or multivessel stent implantation) control angiography may be useful. Medical therapy of risk factors (hyperlipidemia, hypertension, and diabetes mellitus) is essential also after coronary stent implantation. It is important to screen patients for diabetes mellitus, since approximately 1/3 of patients after coronary intervention have an otherwise unrecognized diabetes mellitus or glucose tolerance disturbance.

The +1059G/C polymorphism in the C-reactive protein (CRP) gene is associated with involvement of the terminal ileum and decreased serum CRP levels in patients with Crohn's disease.

BACKGROUND: Serum C-reactive protein (CRP) levels influence the response to anti-tumour necrosis factor (TNF) therapies. AIM: To analyse the influence of the +1059G/C CRP polymorphism on CRP serum levels and disease susceptibility in patients with Crohn's disease (CD). METHODS: Using restriction fragment length polymorphism (RFLP) analysis, genomic DNA from 241 CD patients and 199 unrelated controls was analysed for the +1059G/C substitution in the CRP gene and the common caspase-activation recruitment domain 15 (CARD15) variants. RESULTS: Homozygous C/C carriers were detected only among CD patients (P = 0.066). Patients with ileal involvement (L1 and L3 phenotype) were found in only 58.4% of patients with the wildtype G/G genotype but in 88.2% of the heterozygous G/C carriers (OR 5.26; 95% CI 1.19-23.92) and four of the five C/C homozygous carriers (80%; OR 4.55; 95% CI 1.64-16.67; P = 0.008 for hetero- and homozygous carriers vs. wildtype) which was independent of the presence of CARD15 variants. Increased CD activity was associated with increased CRP serum levels (P < 0.005). For Crohn's disease activity index (CDAI) < 150, C/C homozygosity for the +1059 G/C polymorphism was associated with significantly lower CRP serum levels (P < 0.01). CONCLUSIONS: The C allele of the CRP +1059G/C polymorphism is associated with decreased serum CRP levels and increased likelihood of disease involvement of the terminal ileum in CD patients.

[Regenerative therapy in cardiology: how distant is it from reality?]. / Regenerative Therapien in der Kardiologie: Wie weit entfernt von der Praxis?

During acute myocardial infarction, ischemia causes progressive loss of contractile tissue. Subsequently, structural changes lead to left ventricular remodeling finally resulting in the development of heart failure. In addition to an optimal reperfusion and pharmacologinal post-infarction therapy, increased neovascularization and regeneration of cardiomyocytes could reduce or even abolish the ongoing left ventricular remodeling processes within the infarct area. Experimental studies have demonstrated that transplantation of adult progenitor cells leads to increased neovascularization, reduced fibrosis and, therefore, increased left ventricular function after acute myocardial infarction. In contrast to current treatment strategies, progenitor cell therapy offers a new regenerative approach for myocardial tissue. Initial clinical studies have demonstrated, apart from safety and feasibility of intracoronary infusion of adult autologous progenitor cells, a significant improvement of left ventricular function, geometry and vascularization in patients with acute myocardial infarction receiving intracoronary infusion of progenitor cells. However, in patients with chronic ischemic cardiomyopathy, the improvement in contractility is less pronounced. Finally, whether intracoronary infusion of adult progenitor cells can also reduce morbidity and mortality due to heart failure, remains to be investigated.

Normalization of coronary blood flow in the infarct-related artery after intracoronary progenitor cell therapy: intracoronary Doppler substudy of the TOPCARE-AMI trial.

BACKGROUND: Coronary microvascular dysfunction contributes to infarct extension and poor prognosis after an acute myocardial infarction (AMI). Recently, progenitor cell application has been demonstrated to improve neovascularization and myocardial function after experimental myocardial infarction. Therefore, we investigate coronary blood flow regulation in patients after AMI treated with intracoronary progenitor cell therapy. METHODS AND RESULTS: In the TOPCARE-AMI trial, patients received either bone marrow-derived or circulating progenitor cells into the infarct-related artery 3-7 days after AMI. The present substudy investigates in 40 patients coronary blood flow regulation at the time of progenitor cell therapy and at 4-month follow-up by i.c. Doppler in the infarct artery as well as a reference vessel. At the initial measurement, coronary flow reserve (CFR) was reduced in the infarct artery compared to the reference vessel (median 2.5 vs. 3.4, p<0.001). At 4-month follow-up, intracoronary progenitor cell therapy was associated with a normalization of CFR in the infarct artery (median 3.9 vs. reference vessel 3.8, p=0.15). CFR also improved in the reference vessel, but mechanisms were different: reference vessel increase in CFR was secondary to an increased basal vascular resistance, probably due to reduced need for hypercontractility. In contrast, in the infarct artery, adenosine-induced minimal vascular resistance profoundly decreased, indicating an increased maximal coronary vascular conductance capacity. In addition, in a non-randomized matched control group (n=8), minimal vascular resistance in the infarct artery was significantly elevated compared to progenitor cell treated patients 4 months after AMI (p=0.012). CONCLUSIONS: Intracoronary progenitor cell therapy after AMI is associated with complete restoration of coronary flow reserve due to a substantial improvement of maximal coronary vascular conductance capacity. The clinical importance of improved microcirculation by progenitor cell therapy in patients after AMI has to be established in further randomized trials.

[Diabetes mellitus and coronary artery disease--a high risk combination]. / Diabetes mellitus und koronare Herzkrankheit--eine Risikokombination.

Patients with diabetes mellitus are often not recognized in clinical routine, but also not well characterized in clinical trials. As a diagnostic approach it is recommended to test fasting glucose and glycosylated hemoglobin (HbA1c) in every patient with coronary artery disease (CAD). HbA1c, in addition, provides important prognostic information. Patients with diabetes mellitus do have an enhanced cardiovascular risk in all stages and during all kind of interventions of CAD. However, diabetes is not equal to diabetes; risk modifying factors such as HbA1c, concomitant diseases and medication have to be considered. Absolute benefit of pharmacological therapies is also enhanced in patients with diabetes compared to non-diabetics. However, statins or anti-hypertensive treatment seem to be even more effective in reducing cardiovascular events than pure control of glucose levels alone. During percutaneous interventions (PCI) glycoprotein IIb/IIIa-inhibitors reduce mortality in diabetics, an effect which may be partially also achieved by Clopidogrel. Glitazones reduce restenosis rates; however, clinical end point studies are still ongoing. After PCI, restenosis may be a predictor of mortality in patients with diabetes. Whether drug eluting stents, besides effectively reducing restenosis, may also reduce hard clinical events in patients with diabetes remains to be demonstrated. Current available studies comparing PCI with bypass are limited due to not considered factors (stenosis morphology), randomization bias, and faster progress of technology compared to study termination. During an acute coronary syndrome/myocardial infarction, hyperglycemia is an adverse prognostic marker. However, so far studies using glucose-insulin-potassium (GIK) infusion have not been convincingly demonstrate to be beneficial.

Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging.

BACKGROUND: Experimental and initial clinical studies suggest that transplantation of circulating blood- (CPC) or bone marrow-derived (BMC) progenitor cells may beneficially affect postinfarction remodeling processes after acute myocardial infarction (AMI). To relate functional characteristics of the infused cells to quantitative measures of outcome at 4-month follow-up, we performed serial contrast-enhanced MRI and assessed the migratory capacity of the transplanted progenitor cells immediately before intracoronary infusion. METHODS AND RESULTS: In 28 patients with reperfused AMI receiving either BMCs or CPCs into the infarct artery 4.7+/-1.7 days after AMI, serial contrast-enhanced MRI performed initially and after 4 months revealed a significant increase in global ejection fraction (from 44+/-10% to 49+/-10%; P=0.003), a decrease in end-systolic volume (from 69+/-26 to 60+/-28 mL; P=0.003), and unchanged end-diastolic volumes (122+/-34 versus 117+/-37 mL; P=NS). Infarct size, measured as late enhancement (LE) volume, decreased significantly, from 46+/-32 to 37+/-28 mL (P<0.05). There was a significant correlation between the reduction in LE volume and global ejection fraction improvement. The migratory capacity of transplanted cells as assessed ex vivo toward a gradient of vascular endothelial growth factor for CPCs and stromal cell derived factor-1 for BMCs was closely correlated with the reduction of LE volume. By multivariate analysis, migratory capacity remained the most important independent predictor of infarct remodeling. CONCLUSIONS: Analysis of serial contrast-enhanced MRI suggests that intracoronary infusion of adult progenitor cells in patients with AMI beneficially affects postinfarction remodeling processes. The migratory capacity of the infused cells is a major determinant of infarct remodeling, disclosing a causal effect of progenitor cell therapy on regeneration enhancement.

[Coronary stent implantation in elderly patients: acute and long-term results]. / Koronare Stentimplantation bei alten Patienten. Akutergebnisse und Langzeitverlauf.

UNLABELLED: The number of elderly patients with coronary heart disease is rapidly growing. Morbidity, related with PTCA is increased in elderly patients, presumably because of the more complex adverse baseline characteristics. However, it has not been firmly elucidated whether routine use of coronary stents is associated with a more favourable outcome in this population. Therefore, we investigated the influence of age on acute procedural success, rate of restenosis (quantitative coronary angiography) and major cardiovascular events (death/myocardial infarction [MI]) 6 months after intra-coronary stent implantation in 1306 patients. Patients were categorised into < 65 years (n = 709),65-75 years (n = 443) and >75 years (n= 154). RESULTS: Older patients had a higher amount of multivessel disease (p < 0.001) and a lower left ventricular ejection fraction (p < 0.001). Nevertheless, the rate of acute success and restenosis were comparable between the different age groups. In contrast, older patients had significantly more adverse clinical events during long-term followup. (Death/MI < 65 years 3.0%, 65-75 years 3.9%, > 75 years 7.8%, p = 0.02). However, by multivariate analysis age was no longer an independent predictor of adverse clinical events (p = 0.26), which were predominantly determined by coexisting impaired left ventricular function (p < 0.001). CONCLUSION: After proper judgement of the clinical situation, coronary stent implantation should be considered in selected elderly patients. Thus, advanced age as a solely factor should not be regarded as a contraindication for coronary stent implantation.

Vessel wall MRI of the thoracic aorta: correlation to histology and transesophageal ultrasound. Preliminary results.

PURPOSE: To visualise the vessel wall of the descending thoracic aorta using magnetic resonance imaging. To evaluate the diagnostic potential of tailored T1-weighted sequences with contrast enhancement to assess systemic atherosclerotic disease. METHODS: This study was performed on a clinical 1.5 Tesla scanner using a gradient strength of 30 mT/m and the phased array spine coil. A cadaver was examined to optimise a magnetic resonance imaging (MRI) protocol to evaluate atherosclerotic aortic wall disease. The acquired MR images were compared to gross specimens and histology. Subsequently seven patients who had undergone transesophageal ultrasound (TEU) with detailed assessment of the descending thoracic aorta were examined with MRI. The optimised protocol included untriggered and fat suppressed T2-weighted turbo spin echo sequences and ECG-triggered and fat suppressed T1-weighted spin echo sequences before and after iv administration of Gd-DTPA. Findings of the MR images were compared to the results of TEU. Contrast enhancement measurements were performed in normal and thickened vessel wall segments. RESULTS: For the cadaver study a good correlation of the degree of vessel wall thickening and the extent of plaque imaged with the applied MR protocol was found. Tissue characterisation was limited due to post mortem changes. In vivo ECG-triggered T1-weighted images showed good correlation to TEU in terms of vessel wall thickness and plaque extension as verified by means of consensus reading. Differentiation of the plaque components fat, calcium and fibrous tissue was possible. In thickened aortic wall segments and fibrous caps a mean contrast enhancement of 50.4 % +/- 23.5 % was measurable while normal wall segments showed an enhancement of 6.7 % +/- 3.1 %. The difference of contrast enhancement was highly significant (p < 0.0001). CONCLUSION: Using fat suppressed T1-weighted sequences with contrast enhancement the extent of atherosclerotic vessel wall changes can be demonstrated. The suggested MR protocol contains a high potential for diagnosis and follow-up of therapy of atherosclerotic disease of the descending thoracic aorta.

Statin therapy, inflammation and recurrent coronary events in patients following coronary stent implantation.

OBJECTIVES: We sought to investigate whether statin therapy affects the association between preprocedural C-reactive protein (CRP) levels and the risk for recurrent coronary events in patients undergoing coronary stent implantation. BACKGROUND: Low-grade inflammation as detected by elevated CRP levels predicts the risk of recurrent coronary events. The effect of inflammation on coronary risk may be attenuated by statin therapy. METHODS: We investigated a potential interrelation among statin therapy, serum evidence of inflammation, and the risk for recurrent coronary events in 388 consecutive patients undergoing coronary stent implantation. Patients were grouped according to the median CRP level (0.6 mg/dl) and to the presence of statin therapy. RESULTS: A primary combined end point event occurred significantly more frequently in patients with elevated CRP levels without statin therapy (RR [relative risk] 2.37, 95% CI [confidence interval] [1.3 to 4.2]). Importantly, in the presence of statin therapy, the RR for recurrent events was significantly reduced in the patients with elevated CRP levels (RR 1.27 [0.7 to 2.1]) to about the same degree as in patients with CRP levels below 0.6 mg/dl and who did not receive statin therapy (RR 1.1 [0.8 to 1.3]). CONCLUSIONS: Statin therapy significantly attenuates the increased risk for major adverse cardiac events in patients with elevated CRP levels undergoing coronary stent implantation, suggesting that statin therapy interferes with the detrimental effects of inflammation on accelerated atherosclerotic disease progression following coronary stenting.

Preprocedural C-reactive protein levels and cardiovascular events after coronary stent implantation.

OBJECTIVES: This study assessed the predictive value of preprocedural C-reactive protein (CRP) levels on six-month clinical and angiographic outcome in patients undergoing coronary stent implantation. BACKGROUND: Recent data indicate that low-grade inflammation as detected by elevated CRP serum levels predicts the risk of recurrent coronary events. METHODS: We prospectively investigated the predictive value of preprocedural CRP-levels on restenosis and six-month clinical outcome in 276 patients after coronary stent implantation. The primary combined end point was death due to cardiac causes, myocardial infarction related to the target vessel and repeat intervention of the stented vessel. RESULTS: Grouping patients into tertiles according to preprocedural CRP-levels revealed that, despite identical angiographic and clinical characteristics at baseline and after stent implantation, a primary end point event occurred in 24 (26%) patients of the lowest tertile, in 42 (45.6%) of the middle tertile and in 38 (41.3%) of the highest CRP tertile, p = 0.01. On multivariate analysis, tertiles of CRP levels were independently associated with a higher risk of adverse coronary events (relative risk = 2.0 [1.1 to 3.5], tertile I vs. II and III, p = 0.01) in addition to the minimal lumen diameter after stent (p = 0.04). In addition, restenosis rates were significantly higher in the two upper tertiles compared with CRP levels in the lowest tertile (45.5% vs. 38.3% vs. 18.5%, respectively, p = 0.002). CONCLUSIONS: Low-grade inflammation as evidenced by elevated preprocedural serum CRP-levels is an independent predictor of adverse outcome after coronary stent implantation, suggesting that a systemically detectable inflammatory activity is associated with proliferative responses within successfully implanted stents.

Randomized comparison of coronary stent implantation under ultrasound or angiographic guidance to reduce stent restenosis (OPTICUS Study).

BACKGROUND: Observational studies in selected patients have shown remarkably low restenosis rates after ultrasound-guided stent implantation. However, it is unknown whether this implantation strategy improves long-term angiographic and clinical outcome in routine clinical practice. Methods and Results-- A total of 550 patients with a symptomatic coronary lesion or silent ischemia were randomly assigned to either ultrasound-guided or angiography-guided implantation of

Statin therapy is associated with reduced restenosis rates after coronary stent implantation in carriers of the Pl(A2)allele of the platelet glycoprotein IIIa gene.

Aims Platelets play a central role in the restenosis process by inducing neointimal proliferation after coronary interventions. Glycoprotein IIb/IIIa Pl(A2)polymorphism has been associated with the occurrence of acute coronary syndromes and increased restenosis rates. Statins have been shown to exert potent antiproliferative, antiinflammatory and antithrombotic properties, thereby potentially interfering with the major processes of in-stent restenosis. Therefore, we sought to find out whether statin therapy interferes with restenosis and clinical outcome at 6 months following successful coronary stent implantation in the presence or absence of the Pl(A2)allele. Methods and Results Six hundred and fifty consecutive patients were followed for 6 months after coronary stent insertion. Carriers of the Pl(A2)allele demonstrated a significantly increased restenosis rate, which was abrogated by statin therapy (50.9% vs 28.6%, P=0.01). Moreover, statin therapy was associated with a significant reduction (28.2% vs 49.3%, P<0.01) in the occurrence of major adverse coronary events (myocardial infarction, cardiac death, target vessel revascularization) in the 6 months after the intervention in patients with the Pl(A2)allele. Conclusion Statin therapy reduces increased stent restenosis rates and improves clinical outcome following coronary stent implantation in patients bearing the Pl(A2)allele, suggesting that statins interfere with the functional consequence of a genetically determined platelet-mediated risk factor associated with Pl(A2)polymorphism.

NADH/NADPH oxidase p22 phox gene polymorphism is associated with improved coronary endothelial vasodilator function.

AIMS: The NADH/NADPH oxidase system plays a central role in vascular superoxide anion production, which appears to cause coronary endothelial dysfunction. Recently, it has been suggested that the C242T polymorphism of the NADH/NADPH oxidase p22 phox gene can reduce susceptibility to coronary artery disease. We therefore tested whether this polymorphism is associated with an altered endothelium-dependent vasodilator capacity of human coronary arteries in vivo. METHODS AND RESULTS: The vasodilator function of epicardial arteries in 93 patients was assessed by endothelium-mediated, flow-dependent dilation and nitroglycerin, which is endothelium-independent. NADH/NADPH oxidase p22 phox polymorphism was determined by restriction fragment length polymorphism. Carriers of the CC genotype of the C242T p22 phox polymorphism (n = 44) revealed a significantly blunted endothelium-dependent dilator response (11 +/- 9.2% luminal area change vs 17 +/- 10%;P = 0.007), which was, by multivariate analysis, independent of other risk factors or atherosclerosis itself. There was only a trend towards decreased endothelium-independent dilation in patients bearing the p22 phox CC genotype (P = 0.07). CONCLUSIONS: The C242T polymorphism of the p22 phox gene is an important independent determinant of coronary endothelial vasodilator function. These results provide the first clinical evidence for the functional significance of a polymorphism of a gene related to superoxide anion production in the vascular wall.