[ESC guidelines 2023 on the management of endocarditis : What is new?] / ESC-Leitlinien 2023 zum Management der Endokarditis : Was ist neu?

In August 2023 the new European guidelines on the management of infective endocarditis were published by the European Society of Cardiology (ESC). Numerous recommendations were revised and supplemented by new ones. This review article outlines the essential modifications of the current ESC guidelines focusing on the prevention including antibiotic prophylaxis, the role of the endocarditis team, the revision of the diagnostic criteria, the paradigm shift towards oral antibiotic treatment, the timing and the indications for surgical treatment as well as the relevance of infections of cardiovascular implantable electronic devices.

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.

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.

The Leipzig Prospective Drug-Eluting Balloon-Registry - Outcome of 484 Consecutive Patients Treated for Coronary In-Stent Restenosis and De Novo Lesions Using Paclitaxel-Coated Balloons.

BACKGROUND: Drug-eluting balloons (DEB) are an alternative treatment of in-stent restenosis (ISR), but data regarding outcomes of DEB in de novo lesions are lacking. METHODS AND RESULTS: We investigated the effect of DEB on target lesion revascularization (TLR), procedural complications (coronary dissection/rupture, pericardial effusion, stent thrombosis, peri-interventional NSTEMI, stroke), major adverse cardiac and cerebrovascular events (all-cause mortality, myocardial infarction, TLR, stroke) in patients with ISR and de novo lesions in an all-comers setting. Between April 2009 and October 2013, 484 consecutive patients (mean age 68.4 years; 77.9% male) were enrolled in a prospective registry. TLR rate was 4.9% at 12 months and 8.7% at long-term follow-up of 2.3 years. Subgroup analysis confirmed a TLR rate of 8.9% after DEB treatment of ISR in bare-metal stents (21/235 lesions), 13.0% in drug-eluting stents (21/161 lesions) and 0% for de novo lesions (0/76 lesions). At long-term follow-up, all-cause mortality/cardiac mortality was 8.7% (42/484)/3.3% (16/484) and MACCE rate was 18.4% (89/484 patients), with no differences between DEB for ISR compared with de novo lesions. CONCLUSIONS: DEB for ISR resulted in a low rate of TLR. Our data support DEB in ISR as an effective treatment option. DEB in small coronary vessels in our limited cohort appeared to be safe. Larger, randomized trials in small coronary vessels should be undertaken to verify the long-term results of the current trial.

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

INTRODUCTION: 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. METHODS: Retrospectively, we analyzed all patients who received an orthotopic HTx (n = 298) in our department over a 15-yr period (1997 through 2011) to assess the incidence of post-HTx ECMO implantation, perioperative complications, early and one-yr mortality as well as causes of death. RESULTS: ECMO therapy was utilized to treat graft failure in 28 patients (10.6%) with a mean duration of ECMO support of 4.2 d (six h to 9.4 d). Multivariate analysis revealed as independent predictors for mortality low cardiac output (p = 0.028; odds ratio (OR) = 11.3) and stroke (p = 0.008; OR = 19.7). Cumulative survival rates were 46.4 ± 9.4% within 30 d and 25.0 ± 8.2% at one yr. Causes of death were multiorgan failure (n = 9), sepsis (n = 9), lung failure (n = 2), and intracerebral bleeding (n = 2). ECMO was implanted due to primary graft failure (PGF, n = 16), sepsis (n = 4), and right heart failure (n = 6). CONCLUSION: Temporary ECMO support for postoperative output failure is an acceptable option as a last resort for otherwise doomed patients with fatal graft failure after HTx. The small fraction of patients surviving appear to have a decent long-term prognosis.

Extracellular vesicle species differentially affect endothelial cell functions and differentially respond to exercise training in patients with chronic coronary syndromes.

BACKGROUND: Extracellular vesicles are released upon cellular activation and mediate inter-cellular communication. Individual species of extracellular vesicles might have divergent roles in vascular homeostasis and may show different responses to therapies such as exercise training. AIMS: We examine endothelial effects of medium-size and small extracellular vesicles from the same individual with or without chronic coronary syndrome, and in chronic coronary syndrome patients participating in a four-week high-intensity interval training intervention. METHODS: Human aortic endothelial cells were exposed to medium-size extracellular vesicles and small extracellular vesicles isolated from plasma samples of study participants. Endothelial cell survival, activation and re-endothelialisation capacity were assessed by respective staining protocols. Extracellular vesicles were quantified by nanoparticle tracking analysis and flow cytometry. Extracellular vesicle microRNA expression was quantified by realtime-quantitative polymerase chain reaction. RESULTS: In patients with chronic coronary syndrome (n = 25), plasma counts of leukocyte-derived medium-size extracellular vesicles were higher than in age-matched healthy controls (n = 25; p = 0.04) and were reduced by high-intensity interval training (n = 15; p = 0.01 vs baseline). Re-endothelialisation capacity was promoted by medium-size extracellular vesicles from controls, but not by medium-size extracellular vesicles from chronic coronary syndrome patients. High-intensity interval training for 4 weeks enhanced medium-size extracellular vesicle-mediated support of in vitro re-endothelialisation. Small extracellular vesicles from controls or chronic coronary syndrome patients increased endothelial cell death and reduced repair functions and were not affected by high-intensity interval training. CONCLUSION: The present study demonstrates that medium-size extracellular vesicles and small extracellular vesicles differentially affect endothelial cell survival and repair responses. This equilibrium is unbalanced in patients with chronic coronary syndrome where leukocyte-derived medium-size extracellular vesicles are increased leading to a loss of medium-size extracellular vesicle-mediated endothelial repair. High-intensity interval training partially restored medium-size extracellular vesicle-mediated endothelial repair, underlining its use in cardiovascular prevention and therapy to improve endothelial function.

Novel cardiovascular biomarkers in patients with cardiovascular diseases undergoing intensive physical exercise.

BACKGROUND: In this trial, we analyzed the plasma levels of novel biomarkers that reflect different pathophysiological pathways (sST2: mechanical strain, IGF-BP2: metabolic pathways, suPAR and GDF-15: inflammatory processes) in patients undergoing physical exercise to investigate the effects of training on their plasma concentrations. METHODS: Plasma concentrations of novel biomarkers (sST2, IGF-BP2, suPAR and GDF-15) were analyzed by means of ELISA in patients with stable coronary artery disease (CAD) undergoing four weeks of high- and moderate-intensity training (EXCITE Trial) and in patients with one or more cardiovascular risk factors undergoing eight months of intensive physical exercise (IGF-BP2). Plasma levels of sST2 in patients undergoing eight months of intensive exercise have been published previously by our study group (1.13-fold change, P=0.045). RESULTS: Four weeks of high-intensity exercise training resulted in a statistically significant change in the plasma level of sST2 (1.106-fold change, P=0.0054) and IGF-BP2 (1.24-fold-change, P=0.0165). Eight months of intensive exercise resulted in a significant increase of IGF-BP2 (median 61.2 ng/mL to 80.7 ng/mL, 1.319-fold change, P=0.006). CONCLUSIONS: The significant increase of sST2 after four weeks might be a short-term effect due to the mechanical strain caused by the high-intensity training program, whereas the increase in IGF-BP2 after four weeks and eight months is likely a result of metabolic changes due to physical exercise.

Midterm Durability and Hemodynamic Performance of a Third-Generation Bovine Pericardial Prosthetic Aortic Valve: The Leipzig Experience.

BACKGROUND: The Trifecta valve (St. Jude Medical, St. Paul, MN) is a stented bovine pericardial bioprosthesis for aortic valve replacement (AVR). Implantation experience and midterm follow-up of this valve have not yet been reported from a large single-center cohort. METHODS: We retrospectively analyzed data from 918 patients (73.2 ± 6.5 years; logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE], 13.2 ± 14.3) who underwent AVR. Analyses addressed implantation safety, short- and long-term survival, and hemodynamic valve performance. RESULTS: Concomitant procedures were performed in 54.9% of the patients. Low cardiac output syndrome, postoperative bleeding requiring transfusion or reoperation, and acute renal failure requiring temporary hemodialysis occurred at rates of 4.3%, 7.0%, and 11.7%, respectively. At discharge, 44 patients (4.8%) were identified with moderate prosthesis-patient mismatch (PPM) and none was identified with severe PPM. Mean follow-up was 2.7 ± 1.6 years (maximum, 7.4 years). Survival at 30 days was 88.7% and 92.0% for all patients and patients with isolated AVR, respectively; 5-year overall survival for these groups was 73.4% and 82.2%, respectively. Myocardial infarction (odds ratio [OR], 78; 95% confidence interval [CI], 20.8-294) and inotropic medication (OR, 6.8; 95% CI, 3.2-14.5) were the strongest independent predictors for long-term mortality. Five-year freedom from structural valve deterioration (SVD) was 97.9% ± 1.5%. Left ventricular ejection fraction (LVEF) after implantation was similar to baseline and was stable over time (range, 58.9%-62.3%). The mean gradient improved substantially (39.3 mm Hg at baseline versus 9.4 mm Hg at 6 months). CONCLUSIONS: This large single-center cohort shows the easy and safe implantation, adequate hemodynamic performance, and satisfactory durability of the Trifecta valve at midterm follow-up.

Porcine xenograft for aortic, mitral and double valve replacement: long-term results of 2544 consecutive patients.

OBJECTIVES: The aim of this study was to evaluate the results after stented porcine xenograft implantation with Linx™ anticalcification treatment in the aortic and/or mitral position in elderly patients. METHODS: Over a decade, a total of 2544 patients receiving aortic (AVR = 1920), mitral (MVR = 347) or double valve (DVR = 277) replacement (between November 2001 and March 2012) were evaluated. The study was designed on an 'all comers' basis including all patients with elective, urgent or emergent need for valve replacement. Outcome was assessed by reviewing the prospectively acquired hospital database as well as regular follow-up information obtained by annual written interviews. RESULTS: Mean patient age was 76.5 ± 6 (AVR), 73.8 ± 7 (MVR) and 74.2 ± 7 (DVR) years, respectively; 54.2%/41.9%/42.0% were male, and active endocarditis was diagnosed in 4.5%/19.9%/22.1%; indication for valve surgery and the logistic EUROSCORE I predicted risk for mortality was 15.4 ± 15%/19.9 ± 19%/22.3 ± 21%, respectively. Concomitant mitral valve repair was required in 196 (10.2%) (AVR) patients; coronary artery bypass graft surgery (CABG) in 840 (43.8%) (AVR), 82 (23.7%) (MVR) and 94 (34.1%) (DVR) patients; cryoablation in 232 (12.1%)/81 (23.4%)/67 (24.3%) patients and surgery on the thoracic aorta in 166 (8.7%)/12 (3.5%)/41 (14.9%) patients, respectively. The mean follow-up was 4.5 ± 3.5 years. The rate of freedom from endocarditis after 10 years was 98.3 ± 0.4%/97.5 ± 1.0%/97.4 ± 1.6% (P = n.s.). The rate of freedom from structural valve disease was 96.3 ± 0.6%/93.8 ± 2.4%/92.8 ± 2.2% (AVR versus DVR, P = 0.009), and from thromboembolic events was 94.8 ± 1.0%/91.5 ± 2.9%/97.9 ± 1.3%. The 30-day survival rate was 97.3 ± 0.4%/95.1 ± .1.2%/92.8 ± 1.6% and the 10-year survival rate was 42.1 ± 1.5%/33.9 ± 4.7%/22.1 ± 7.1%, respectively. CONCLUSIONS: The Epic™ stented porcine xenograft is associated with acceptable survival, with large proportions of patients free from valve-related complications and freedom from valve reintervention for all older, in-coming patients.

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.

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.

Bilateral versus single lung transplant for idiopathic pulmonary fibrosis.

OBJECTIVES: It is unknown if uni- or bilateral lung transplant is best for treatment of usual idiopathic pulmonary fibrosis. We reviewed our single-center experience comparing both treatments. MATERIALS AND METHODS: Between 2002 and 2011, one hundred thirty-eight patients at our institution underwent a lung transplant. Of these, 58 patients presented with idiopathic pulmonary fibrosis (56.9%) and were the focus of this study. RESULTS: Thirty-nine patients received a single lung transplant and 19 patients a bilateral sequential lung transplant. The mean patient age was 54 ± 10 years, and 69% were male. The intraoperative course was uneventful, save for 7 patients who needed extracorporeal membrane oxygenation support. Three patients had respiratory failure before the lung transplant that required mechanical ventilation and was supported by extracorporeal membrane oxygenation. Elevated pulmonary artery pressure > 40 mm Hg was identified as an independent predictor of early mortality by uni- and multivariate analysis (P = .01; OR 9.7). Using a Cox regression analysis, postoperative extracorporeal membrane oxyge-nation therapy (P = .01; OR 10.2) and the need for > 10 red blood cell concentrate during the first 72 hours after lung transplant (P = .01; OR 5.6) were independent predictors of long-term survival. Actuarial survival at 1 and 5 years was 65.6% and 55.3%, with no significant between-group differences (70.6% and 54.3%). CONCLUSIONS: Lung transplant is a safe and curative treatment for idiopathic pulmonary fibrosis. According to our results, unilateral lung transplant for idiopathic pulmonary fibrosis is an alternative to bilateral lung transplant and may affect the allocation process.

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.

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.

BACKGROUND: Exercise 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/DESIGN: The 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. DISCUSSION: The 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 REGISTRATION: Clinical trial registration information-URL: http://www.clinicaltrials.gov.Unique identifier: NCT01209637.

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.