Madlen Uhlemann

The Leipzig Prospective Vascular Ultrasound Registry in Radial Artery Catheterization: Impact of Sheath Size on Vascular Complications

OBJECTIVES This study investigated the impact of sheath size on the rate of radial artery occlusions (RAO) (primary objective) and other access site complications (hemorrhage, pseudoaneurysm, arteriovenous fistula) as secondary objectives after transradial coronary catheterization. BACKGROUND The number of vascular access complications in the published data ranges from 5% to 38% after transradial catheterization. METHODS Between November 2009 and August 2010, 455 patients 65.3 ± 10.9 years of age (62.2% male) with transradial access with 5-F (n = 153) or 6-F (n = 302) arterial sheaths were prospectively recruited. Duplex sonography was obtained in each patient before discharge. Patients with symptomatic RAO were treated with low-molecular-weight heparin (LMWH), and a follow-up was performed. RESULTS The incidence of access site complications was 14.4% with 5-F sheaths compared with 33.1% with 6-F sheaths (p < 0.001). Radial artery occlusion occurred in 13.7% with 5-F sheaths compared with 30.5% with 6-F sheaths (p < 0.001). There was no difference between groups with regard to hemorrhage, pseudoaneurysms, or arteriovenous fistulas. Female sex, larger sheath size, peripheral arterial occlusive disease, and younger age independently predicted RAO in multivariate analysis. In total, 42.5% of patients with RAO were immediately symptomatic; another 7% became symptomatic within a mean of 4 days. Of patients with RAO, 59% were treated with LMWH. The recanalization rates were significantly higher in patients receiving LMWH compared with conventional therapy (55.6% vs. 13.5%, p < 0.001) after a mean of 14 days. CONCLUSIONS The incidence of RAO by vascular ultrasound was higher than expected from previous data, especially in patients who underwent the procedure with larger sheaths.

Circulating microRNA-126 increases after different forms of endurance exercise in healthy adults

Background MicroRNAs (miRNAs) are small non-coding molecules regulating gene expression. Recently circulating miRNAs could be detected in the plasma, serving as novel biomarkers. Different forms of exercise mobilize progenitor cells from the bone marrow, helping in tissue repair. Data of different forms of exercise on endothelial cell damage are lacking. The aim of the study was to evaluate the impact of different exercise modalities on the plasma concentration of miRNA-126, as a marker for endothelial damage. Methods The plasma concentration of miRNA-126 and miRNA-133 (marker for muscle damage) was assessed by qRT-PCR analysis in plasma samples from healthy individuals performing one of the following exercise tests: (1) maximal symptom-limited exercise test, (2) bicycling for 4 h, (3) running a marathon, and (4) resistance exercise. Results A maximal symptom-limited exercise test resulted in a significant increase of circulating miRNA-126 at maximum power (2.1-fold versus begin), whereas the concentration of miRNA-133 remained unchanged. In line, four hours of cycling increased plasma concentration of miRNA-126 with a maximum 30 minutes after begin (4.6-fold versus begin) without an impact on miRNA-133 concentration. Finishing a marathon race resulted in an increase of miRNA-126 and miRNA-133. In contrast, eccentric resistance training led to an isolated increase of miRNA-133 level (2.1-fold versus begin) with unchanged miRNA-126. Conclusion Different endurance exercise protocols lead to damage of the endothelial cell layer as evident by an increase in miRNA-126. On the other hand, resistance exercise has no impact on the endothelial cells, but leads to a destruction of muscular cells.

Role of endothelial progenitor cells in the beneficial effects of physical exercise on atherosclerosis and coronary artery disease

In clinical trials as well as in several animal experiments it is evident that physical exercise is a powerful tool to positively influence the development and/or progression of atherosclerosis and coronary artery disease (CAD). The main target of physical exercise seems to be the maintenance of an intact endothelial cell layer. Since the discovery that endothelial progenitor cells (EPCs) are present in the circulation and the knowledge that exercise, either as a single exercise bout or an exercise training program, have the potency to mobilize EPCs from the bone marrow, the contribution of the EPCs for the preservation or repair of the endothelial cell layer is still under debate. Either the EPCs differentiate into mature endothelial cells, or they stimulate via a paracrine mechanism mature endothelial cells to proliferate. It is still unclear, if the exercise-induced mobilization of EPCs is casually related to the improvement of endothelial function. This review will discuss the role of endothelial progenitor cells in the beneficial effects of physical exercise on atherosclerosis and coronary artery disease.

Coronary Collateral Growth Induced by Physical Exercise Results of the Impact of Intensive Exercise Training on Coronary Collateral Circulation in Patients With Stable Coronary Artery Disease (EXCITE) Trial

Background— A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease. However, the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear. Methods and Results— This prospective, open-label study randomly assigned 60 patients with significant coronary artery disease (fractional flow reserve ⩽0.75) to high-intensity exercise (group A, 20 patients) or moderate-intensity exercise (group B, 20 patients) for 4 weeks or to a control group (group C, 20 patients). The primary end point was the change of the coronary collateral flow index (CFI) after 4 weeks. Analysis was based on the intention to treat. After 4 weeks, baseline CFI increased significantly by 39.4% in group A (from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks) in comparison with 41.3% in group B (from 0.143±0.06 to 0.202±0.09), whereas CFI in the control group remained unchanged (0.7%, from 0.149±0.09 to 0.150±0.08). High-intensity exercise did not lead to a greater CFI than moderate-intensity training. After 4 weeks, exercise capacity, VO2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B. Conclusions— A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01209637.

Coronary Collateral Growth Induced by Physical Exercise: Results of the Leipzig EXerCIse Training versus MEdical Management in Patients With Stable Coronary Artery Disease (EXCITE) Trial

Background— A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease. However, the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear. Methods and Results— This prospective, open-label study randomly assigned 60 patients with significant coronary artery disease (fractional flow reserve ⩽0.75) to high-intensity exercise (group A, 20 patients) or moderate-intensity exercise (group B, 20 patients) for 4 weeks or to a control group (group C, 20 patients). The primary end point was the change of the coronary collateral flow index (CFI) after 4 weeks. Analysis was based on the intention to treat. After 4 weeks, baseline CFI increased significantly by 39.4% in group A (from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks) in comparison with 41.3% in group B (from 0.143±0.06 to 0.202±0.09), whereas CFI in the control group remained unchanged (0.7%, from 0.149±0.09 to 0.150±0.08). High-intensity exercise did not lead to a greater CFI than moderate-intensity training. After 4 weeks, exercise capacity, VO2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B. Conclusions— A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01209637.

Molecular effects of exercise training in patients with cardiovascular disease: focus on skeletal muscle, endothelium, and myocardium

For decades, we have known that exercise training exerts beneficial effects on the human body, and clear evidence is available that a higher fitness level is associated with a lower incidence of suffering premature cardiovascular death. Despite this knowledge, it took some time to also incorporate physical exercise training into the treatment plan for patients with cardiovascular disease (CVD). In recent years, in addition to continuous exercise training, further training modalities such as high-intensity interval training and pyramid training have been introduced for coronary artery disease patients. The beneficial effect for patients with CVD is clearly documented, and during the last years, we have also started to understand the molecular mechanisms occurring in the skeletal muscle (limb muscle and diaphragm) and endothelium, two systems contributing to exercise intolerance in these patients. In the present review, we describe the effects of the different training modalities in CVD and summarize the molecular effects mainly in the skeletal muscle and cardiovascular system.

Extracorporeal membrane oxygenation: experience in acute graft failure after heart transplantation

Acute graft failure is the leading cause of early mortality after heart transplantation (HTx). Extracorporeal membrane oxygenation (ECMO) is an efficient therapeutic option to treat various pathologies, unburden the left and right ventricle, and allow for functional recovery of the transplanted heart. We reviewed our ECMO experience and outcomes in HTx patients.

Fate of patients with extracorporeal lung assist as a bridge to lung transplantation versus patients without – a single-center experience

Objectives: Mechanical lung assist (MLA; extracorporeal membrane oxygenation (ECMO) or extracorporeal lung assist (ECLA)) is increasingly used as a temporary bridge to lung transplantation (LTx). This study was designed to evaluate the impact of preoperative MLA on the operative outcome, including longer-term survival, in comparison to patients undergoing LTx without preoperative MLA. Methods: A total of 143 patients underwent LTx at our institution from 2002 to 2011. Forty-three percent (n=62) of patients presented with idiopathic pulmonary fibrosis and 71% (n=102) presented with severely elevated pulmonary artery pressure. Results: Thirteen patients (9.1%) required pre-LTx MLA support (age 44 ±13 years, double LTx 73.3%, female gender 53%) whereas 130 patients did not (age 52 ±11 years, double LTx 41.5%, female gender 36.9%). In one patient, MLA was successfully weaned and the patient underwent subsequent LTx. All patients in the MLA group were intraoperatively supported with continuous ECMO. One patient had to be supported with MLA after LTx for a period of 8 days. The short-term and mid-term postoperative survival of the MLA patient group was not significantly different from the non-MLA group (LogRank p=0.28). The 30-day, 90-day and 1-year survivals were 95%, 90% and 71%, respectively, in the patients without MLA compared to 85%, 77% and 68% in the MLA group. Conclusions: MLA has no impact on long-term survival rate in LTx patients, but has an influence in postoperative survival. MLA support is a valuable tool to bridge unstable patients to LTx.

Minimally invasive aortic valve replacement: the Leipzig experience

Background: Minimally invasive techniques are progressively challenging traditional approaches in cardiothoracic surgery. Minimally invasive aortic valve replacement (AVR) has become a routine procedure at our institution. Methods: We retrospectively analyzed all patients undergoing minimally invasive isolated AVR between January 2003 and March 2014, at our institution. Mean follow-up was 4.7±4.3 years (range: 0-18 years) and was 99.8% complete. Results: There were 1,714 patients who received an isolated minimally invasive AVR. The mean (± SD) patient age was 65±12.8 years, ejection fraction 60%±12% and log EuroSCORE 5.3%±5.1%. Mean cross-clamp time was 58±18 minutes and mean cardiopulmonary bypass (CPB) time was 82.9±26.7 minutes. Thirty-day survival was 97.8%±0.4%, and 69.4%±1.7% at 10-years. The multivariate analysis revealed age at surgery [P=0.016; odds ratio (OR), 1.1], length of surgery time (P=0.002; OR, 1.01), female gender (P=0.023; OR, 3.54), preoperative myocardial infarction (MI) (P=0.006; OR, 7.87), preoperative stroke (P=0.001; OR, 13.76) and preoperative liver failure (P=0.015; OR, 10.28) as independent risk factors for mortality. Cox-regression analysis revealed the following predictors for long term mortality: age over 75 years (P<0.001; OR, 3.5), preoperative dialysis (P<0.01; OR, 2.14), ejection fraction less than 30% (P=0.003; OR, 3.28) and urgent or emergency operation (P<0.001; OR, 2.3). Conclusions: Minimally invasive AVR can be performed safely and effectively with very few perioperative complications. The early and long-term outcomes in these patients are acceptable.

Impact of different exercise training modalities on the coronary collateral circulation and plaque composition in patients with significant coronary artery disease (EXCITE trial): study protocol for a randomized controlled trial

BackgroundExercise training (ET) in addition to optimal medical therapy (OMT) in patients with stable coronary artery disease (CAD) has been demonstrated to be superior to percutaneous coronary interventions (PCI) with respect to the composite endpoint of death, myocardial infarction, stroke, revascularization and hospitalization due to worsening of angina. One mechanism leading to this superiority discussed in the literature is the increase in coronary collateral blood flow due to ET. Until now, data demonstrating the positive effect of ET on the collateral blood flow and the functional capacity of the coronary collateral circulation are still lacking.Methods/designThe EXCITE trial is a three-armed randomized, prospective, single-center, open-label, controlled study enrolling 60 patients with stable CAD and at least one significant coronary stenosis (fractional flow reserve ≤0.75). The study is designed to compare the influence and efficacy of two different 4-week ET programs [high-intensity interval trainings (IT) versus moderate-intensity exercise training (MT) in addition to OMT] versus OMT only on collateral blood flow (CBF). The primary efficacy endpoint is the change of the CBF of the target vessel after 4 weeks as assessed by coronary catheterization with a pressure wire during interruption of the antegrade flow of the target vessel by balloon occlusion. Secondary endpoints include the change in plaque composition as assessed by intravascular ultrasound (IVUS) after 4 weeks, myocardial perfusion as analyzed in MRI after 4 weeks and 12 months, peak oxygen uptake (V02 peak), change in endothelial function and biomarkers after 4 weeks, 3, 6 and 12 months. The safety endpoint addresses major adverse cardiovascular events (death from cardiovascular cause, myocardial infarction, stroke, TIA, target vessel revascularization or hospitalization) after 12 months.DiscussionThe trial investigates whether ET for 4 weeks increases the CBF in patients with significant CAD compared to a sedentary control group. It also examines the impact of two intensities of ET on the CBF as well as the histological plaque composition. The trial started recruitment in June 2009 and will complete recruitment until June 2012. First results are expected in December 2012 (4-week follow-up), final results (12-month long-term secondary endpoint) in December 2013.Trial registrationClinical trial registration information-URL: http://www.clinicaltrials.gov.Unique identifier: NCT01209637