Management of anticoagulation in patients with infective endocarditis.

Infective endocarditis (IE) carries a high risk of vascular complications (e.g., cerebral embolism, intracerebral hemorrhage, and renal infarction), which are correlated with increased early and late mortality. Although anticoagulation is the cornerstone for management of thromboembolic complications, it remains controversial and challenging in patients with IE. An appropriate anticoagulation strategy is crucial to improving outcomes and requires a good understanding of the indication, timing, and regimen of anticoagulation in the setting of IE. Observational studies have shown that anticoagulant treatment failed to reduce the risk of ischemic stroke in patents with IE, supporting that IE alone is not an indication for anticoagulation. In the absence of randomized controlled trials and high-quality meta-analyses, however, current guidelines on IE were based largely on observational data and expert opinion, providing few specific recommendations on anticoagulation. A multidisciplinary approach and patient engagement are required to determine the timing and regimen of anticoagulation in patients with IE, especially in specific situations (e.g., receiving warfarin anticoagulation at the time of IE diagnosis, cerebral embolism or ischemic stroke, intracerebral hemorrhage, or urgent surgery). Collectively, individualized strategies on anticoagulation management of IE should be based on clinical evaluation, available evidence, and patient engagement, and ultimately be developed by the multidisciplinary team.

[Recommendations of the S3 Guideline "Use of Extracorporeal Circulation (ECLS/ ECMO) for Cardiac and Circulatory Failure" of the Association of Scientific Medical Societies in Germany]. / Empfehlungen der S3-Leitlinie (AWMF) "Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen".

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

Prenatal nicotine exposure induces gender-associated left ventricular-arterial uncoupling in adult offspring.

Alterations in vascular or myocardial structure and function have been demonstrated in offspring subjected to prenatal nicotine exposure (PNE), however, limited data are available on how these changes interact. The present study assessed the hypothesis that prenatal nicotine exposure induced gender-specific alterations of left ventricular-arterial coupling indices in adult offspring. Female Sprague-Dawley rats were exposed to either nicotine (8 mg/kg/day) or saline via subcutaneous osmotic mini-pumps throughout gestation. Male and female offspring, aged 12 months, underwent non-invasive echocardiography and invasive left ventricular cannulation. Left ventricular-arterial coupling was analysed as the ratio of effective arterial elastance (Ea) to ventricular end-systolic elastance (Ees). The left ventricular myocardium and aorta were stained with hematoxylin and eosin and the myocardial cell cross-sectional area was calculated. Simultaneously, the ratio of medium thickness to internal diameter in the aorta and mesenteric artery was determined. The fibrosis component of left ventricle myocardium was analyzed by Sirius-red staining and further confirmed by hydroxyproline determination. The elastic properties of the aortic wall were analyzed by van Gieson staining. PNE caused significant increases in pulse pressure (56.36 ± 7.41 vs. 50.16 ± 4.94 mmHg; P<0.05) and left ventricular meridional wall stress (78.25 ± 9.12 vs. 69.64 ± 7.58 kdyne/cm(2); P<0.05) in male offspring compared with the control. Conversely, no similar effect was observed in female offspring. An elevated augmentation index was noted in male and female pups. Additionally, Ea/Ees was reduced in PNE males compared with control males, due to a disproportionate increase in Ees vs. Ea whereas in females, Ea/Ees did not differ significantly due to tandem increase in Ea and Ees. In addition, collagen cross-linking was markedly higher in male offspring, whereas it was unaltered in females compared with their respective controls. Fragmentation of the elastic network in the aorta and the increased ratio of medial thickness to internal diameter in the mesenteric artery were more evident in male offspring when compared with female offspring. PNE caused combined ventricular-arterial stiffening in male and female offspring, with lower Ea/Ees in males, while Ea/Ees was preserved in females. Enhanced collagen cross-linking in the myocardium, underdeveloped elastic fibers in the aorta and remodeled resistance vessels were associated with pathological ventricular arterial mismatching. The results of the present study indicated that male offspring were more susceptible to the development of ventricular and arterial dysfunction in response to PNE compared with female offspring.

An insight into short- and long-term mechanical circulatory support systems.

Cardiogenic shock due to acute myocardial infarction, postcardiotomy syndrome following cardiac surgery, or manifestation of heart failure remains a clinical challenge with high mortality rates, despite ongoing advances in surgical techniques, widespread use of primary percutaneous interventions, and medical treatment. Clinicians have, therefore, turned to mechanical means of circulatory support. At present, a broad range of devices are available, which may be extracorporeal, implantable, or percutaneous; temporary or long term. Although counter pulsation provided by intra-aortic balloon pump (IABP) and comprehensive mechanical support for both the systemic and the pulmonary circulation through extracorporeal membrane oxygenation (ECMO) remain a major tool of acute care in patients with cardiogenic shock, both before and after surgical or percutaneous intervention, the development of devices such as the Impella or the Tandemheart allows less invasive forms of temporary support. On the other hand, concerning mid-, or long-term support, left ventricular assist devices have evolved from a last resort life-saving therapy to a well-established viable alternative for thousands of heart failure patients caused by the shortage of donor organs available for transplantation. The optimal selection of the assist device is based on the initial consideration according to hemodynamic situation, comorbidities, intended time of use and therapeutic options. The present article offers an update on currently available mechanical circulatory support systems (MCSS) for short and long-term use as well as an insight into future perspectives.

Prognostic relevance of heart rate at rest for survival and the quality of life in patients with dilated cardiomyopathy.

OBJECTIVES: Reduction of resting heart rate (HR) has been suggested as a novel therapeutic approach in patients with chronic heart failure because it has been shown to prolong survival and also to improve health-related quality of life (Hr-QoL). The purpose of this analysis was to assess the prognostic impact of resting HR in patients with dilated cardiomyopathy (DCM). METHODS: 217 patients with DCM confirmed by endomyocardial biopsy were investigated (age 49 ± 11 years, 20.7 % were female). The study population was divided into two groups according to the median of the resting HR. After a median follow-up time of 7.4 years overall survival and health-related quality of life (Hr-QoL) were compared in both groups. Survival was compared using Kaplan-Meier method and Hr-QoL was assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). RESULTS: Elevated resting HR was associated with poor 1-year survival (p = 0.03). In contrast, long-term survival was not affected by HR (p = 0.20). Patients with lower HR at rest scored significantly lower on the MLHFQ (20 vs. 36, p = 0.03), indicating that higher resting HR is associated with an impairment of Hr-QoL. CONCLUSIONS: Increased HR might be used as a diagnostic tool to identify patients at risk. Reduction of resting HR in patients with DCM might be a therapeutic option to improve Hr-QoL and therefore merits further investigation in future studies.

Valve-in-valve transcatheter aortic valve implantation for degenerated bioprosthetic heart valves.

OBJECTIVES: We sought to analyze outcomes of patients with degenerated surgically implanted bioprosthetic heart valves undergoing valve-in-valve (viv) transcatheter aortic valve implantation (TAVI). BACKGROUND: Redo cardiac surgery for degenerated bioprosthetic heart valves is associated with increased risks, particular in elderly patients with comorbidities. For these patients, TAVI may be an attractive, less invasive treatment option. METHODS: Data from 47 patients age 64 to 97 years (logistic euroSCORE: 35.0 ± 18.5%) undergoing transfemoral (n = 25) or transapical (n = 22) viv-TAVI for failed bioprosthetic aortic valves 113 ± 65 months after initial surgery at 9 clinical sites in Germany and Switzerland were analyzed. RESULTS: Valve-in-valve TAVI was technically successful in all patients, with 2 patients requiring bailout implantation of a second TAVI prosthesis for severe regurgitation during the procedure. There was 1 procedural death as the result of low-output failure. Valvular function after viv-TAVI was excellent with respect to valve competence, but increased transvalvular gradients ≥20 mm Hg were noted in 44% of patients. Vascular access complications occurred in 6 (13%) patients, and 5 (11%) patients required new pacemaker implantation after viv-TAVI. Renal failure requiring dialysis occurred in 4 (9%) patients. Mortality at 30 days was 17% (1 procedural and 7 post-procedural deaths), with 3 of 8 fatalities the result of non-valve-related septic complications. CONCLUSIONS: Valve-in-valve TAVI can be performed with high technical success rates, acceptable post-procedural valvular function, and excellent functional improvement. However, in these predominantly elderly high-risk patients with multiple comorbidities, viv-TAVI was associated with 17% mortality, often because of septic complications arising in the post-operative phase.

Better outcome after cardiopulmonary resuscitation using percutaneous emergency circulatory support in non-coronary patients compared to those with myocardial infarction.

BACKGROUND & OBJECTIVES: Mobile heart-lung-machines applied by percutaneous cannulation are mostly used in patients suffering from acute myocardial infarction (AMI). Whether patients with non-coronary reasons for circulatory arrest benefit of percutaneous emergency circulatory support (PECS) in the same way is still unclear. METHODS: We included 22 consecutive patients who were treated by PECS during a registry period of two years. Primary study endpoint was 30-day mortality rate. RESULTS: Circulatory arrest was caused by AMI in 14 patients (64%). The remaining 8 patients suffered from cardiomyopathy/myocarditis, 4; pulmonary embolism, 2; acute pulmonary failure, 1; and tumor lysis syndrome, 1. Revascularization rate was 93% in the AMI group under PECS support. Overall survival rate was 36.4% at one month: it reached 62.5% among non-coronary patients, but only 21.4% in the AMI group (P = 0.02). Weaning was possible by direct heart transplantation in two patients. Additional two patients required implantation of a left ventricular assist device. Pumpless extracorporeal lung assist was used in one case. CONCLUSION: In this small retrospective study percutaneous emergency circulatory support provided sufficient hemodynamic stabilization in emergency situations. One fifth of AMI patients were saved by immediate restoration of circulation and causal treatment when other means of resuscitation failed. Higher survival rates were noted in non-coronary patients.

Percutaneous caval stent valve implantation: investigation of an interventional approach for treatment of tricuspid regurgitation.

AIMS: Severe tricuspid regurgitation (TR) reduces cardiac output (CO) and increases central venous pressure leading to secondary organ dysfunction. To date, the open surgical approach is the only option to treat TR. Herein, we report our experience of treatment by percutaneous implantation of valved stents in the inferior vena cava (IVC) and superior vena cava (SVC) to substitute tricuspid valve function in a model of acute insufficiency. METHODS AND RESULTS: Acute TR grades III-IV was created in 13 sheep (54-75 kg) via papillary muscle and chordae avulsion using a 0.07 inch wire blade. Successful creation of TR was confirmed using angiography and by a prominent ventricular wave in central venous pressure recording. Two self-expanding nitinol stents containing a porcine pulmonary valve were then implanted in the IVC and SVC in a transcatheter approach. Implantation was performed through the right jugular vein by means of a 21 F catheter and guided by fluoroscopy. Haemodynamics were continuously monitored and valve function was verified by angiography and epicardial echocardiography. After successful implantation and proof of concept in the acute study (acute group, n = 9), chronic studies were (n = 4, 4 weeks follow-up) performed. Tricuspid regurgitation grades III-IV was successfully created in all animals and resulted in a significant reduction of CO. A ventricular wave in the IVC of 16.2 +/- 2.33 mmHg (acute group) and 14.9 +/- 1.71 mmHg (chronic group) confirmed the presence of severe TR. After deployment of the IVC and the SVC valve, the ventricular wave in the IVC significantly decreased to 13.9 +/- 2.97 mmHg (acute group) and 12.7 +/- 1.15 (chronic group), whereas CO significantly increased to 4.20 +/- 0.84 L/min (acute group) and 5.4 +/- 0.67 L/min (chronic group). At autopsy, correct device position was verified in all successfully implanted animals, no macroscopic damage resulting from the implantation procedure was observed. CONCLUSION: In high-grade tricuspid insufficiency, percutaneous implantation of valved stents in the central venous position reduces venous regurgitation and improves haemodynamics in the animal experiment. Implantation of one or two valves in central venous position is technically feasible. Functional replacement of the insufficient tricuspid valve leads to an increase in CO. This technique expands the potential therapeutic options for patients with relevant tricuspid valve regurgitation having a high risk for open heart surgery.

Endothelial progenitor cells in adolescents: impact of overweight, age, smoking, sport and cytokines in younger age.

BACKGROUND AND AIMS: Endothelial progenitor cells (EPCs) are bone marrow derived pluripotent vascular progenitor cells capable to contribute to re-endothelialization and neovascularization. The number of circulating EPCs has been established as a biomarker of cardiovascular risk and is known to decrease with age. We determined the number of EPCs in teenagers and evaluated the influence of traditional risk factors focusing on overweight. METHODS: 79 male adolescents were enrolled (age 13-17 years; 42 of normal weight: 64.1 +/- 7.6 kg; 37 above the 90th BMI-percentile: 96.9 +/- 20.5 kg). 41 healthy adults served as controls. EPCs were counted by flow cytometry (CD34+/-CD133/KDR). Besides traditional risk factors, cholesterol, and high sensitive CRP different cytokines were determined. RESULTS: Overweight adolescents have a higher systolic blood pressure, higher hsCRP, higher HbA(1c) and lower HDL. The number of CD34-negative EPCs, but not CD34-positive EPCs is higher in overweight adolescents. The overall level of EPCs is lower in adolescents compared to adults. CONCLUSIONS: Overweight in adolescents influences EPCs in early life. CD34-negative EPCs might be more sensitive to the early risk profile and may represent a biological marker of occult vascular damage. Beginning insulin resistance, endothelial damage and elevation of EPCs could indicate the higher risk for future cardiovascular disease in obese teenagers.

Providing macro- and microcirculatory support with the Lifebridge System during high-risk PCI in cardiogenic shock.

High-risk percutaneous procedures are necessary in patients with contraindications to surgery in whom the inherent risk of the underlying disease is very high. Circulatory support may be provided with an intra-aortic balloon pump. If active cardiac support is required different devices have been successfully used. We report the case of a 75-year-old patient admitted in cardiogenic shock with a severe coronary three-vessel disease with distal left main stenosis. The ejection fraction was 23%. The high-risk PCI of the distal left main coronary artery and left circumflex artery PCI as the main supplying vessel was supported by Lifebridge (Lifebridge Medizintechnik GmbH, Ampfing, Germany), a new portable mechanical circulatory support system. During the procedure we evaluated the macro- and microcirculation. The complex procedure succeeded with a flow of 2-2.5l providing both adequate macro- and microcirculation.

Acute and long-term outcome of unprotected left main coronary angioplasty compared to the anticipated surgical risk.

OBJECTIVES: Percutaneous coronary intervention of unprotected left main (ULM) stenosis is increasing despite surgical revascularisation being the recommended treatment by the current guidelines. We compared the 30-day and 9-month mortality after ULM stenting with the predicted surgical outcome as determined by the EuroSCORE. METHODS AND RESULTS: We included 81 consecutive patients who underwent ULM stenting. The patient cohort was divided into a normal risk group (EuroSCORE 5, predicted 30-day mortality 11%). Follow-up examinations were scheduled for one and nine months after the initial PCI. The average EuroSCOREs in the normal- and high-risk group were 3.0 (29 patients, 36%) and 10.0 (52 patients, 64%), respectively. Mortality rates at 30 days were 3% in the normal-risk group and 8% in the high-risk group. Subacute stent thrombosis occurred in 3.4% (three patients) undergoing elective PCI. Major adverse cardiac events during the nine months follow-up were registered in 24% of patients in the normal-risk group, and in 27% of the patients in the high-risk group. CONCLUSION: Short-term outcome of ULM stenting in our high-risk patients is comparable to surgical outcome predicted by the EuroSCORE. Long-term outcome was less favourable due to a high mortality rate. ULM stenting in patients with low surgical risk could be associated with higher mortality rates compared to CABG because of the unpredictable risk of a fatal stent thrombosis.

First use of a novel plug-and-play percutaneous circulatory assist device for high-risk coronary angioplasty.

OBJECTIVES: Novel circulatory assist devices provide hemodynamic stability in high risk coronary interventions. They ensure sufficient organ perfusion during transfer in case of procedural failure or cardiogenic arrest. We describe the first human use of a novel plug-and-play circulatory assist device for high risk coronary angioplasty. METHODS: An 84 year old lady suffered syncope with complex fracture of the left forearm. Her syncope was related to a subtotal stenosis of the left main coronary artery associated with an acute myocardial infarction. Additional risk factors were previous cardiac surgery, pulmonary disease, diabetes mellitus, and renal insufficiency. Coronary angiography revealed stenosis of both coronary ostia. The emergency assist device LIFEBRIDGE was connected with the patient's circulation by percutaneous cannulation (15F and 17F) of the femoral artery and vein. RESULTS: Stent implantation was performed in both coronary ostia by Judkin's technique. The cannulas were removed two hours after the intervention by local compression. Osteosynthesis of the left radius and ulna was performed five days later under regional anesthesia. The patient was discharged without any complains on day 10. CONCLUSION: This case illustrates the safe and easy use of a novel plug-and-play percutaneous circulatory assist device for high risk interventions. It may be recommended for use in emergency situations.

[Invasive therapeutic strategies in acute heart failure complicating coronary artery disease: effectiveness and boundaries]. / Möglichkeiten und Grenzen der interventionellen Therapie bei akuter Herzinsuffizienz bei koronarer Herzerkrankung.

Acute heart failure and especially its most severe form, cardiogenic shock, remain the final common pathway to death in a substantial number of patients with acute myocardial infarction (MI). Several studies demonstrated that mechanical reperfusion of occluded coronary arteries by percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery improves survival in patients with acute MI and cardiogenic shock. There is strong evidence that intraaortic balloon pump (IABP) support and ventricular assist devices can stabilize hemodynamics in these patients so that revascularization procedures can be safely performed. This article provides an overview of the therapeutic strategies for acute MI with cardiogenic shock, with focus on the role and particularities of different devices used as mechanical circulatory support in these patients.

The functional reserve of collaterals supplying long-term chronic total coronary occlusions in patients without prior myocardial infarction.

AIMS: Chronic total coronary occlusions (CTOs) with angiographically well-developed collaterals may be considered to provide sufficient blood supply to the occluded segment, and the indication for revascularization may be questioned. Therefore, the collateral function and functional reserve in patients with a CTO without a prior Q-wave myocardial infarction (MI) were assessed. METHODS AND RESULTS: Invasive assessment of collateral function was done during successful percutaneous coronary intervention in 107 patients with a CTO and no prior Q-wave MI. Intracoronary Doppler flow velocity and pressure recordings were obtained distal to the occlusion before the first balloon inflation and collateral function indexes calculated. In 62 patients, additional pharmacological stress testing was done by intravenous adenosine (140 microg/kg/min) to assess the collateral flow reserve. Patients with normal and impaired regional dysfunction were compared. Collateral function was similar in patients with and without regional left ventricular (LV) dysfunction. In both groups, 78% collaterals provided a collateral pressure index at baseline > 0.3, sufficient to prevent ischaemia during a balloon occlusion, with a minimum of 0.2 in those with preserved LV function. A Doppler-derived function index showed a wider variation due to the high prevalence of microvascular dysfunction in CTOs. Only 7% of patients had an increase in collateral flow reserve > 2.0 during pharmacological stress, whereas coronary steal occurred in one-third independent of regional LV function. CONCLUSION: A limited increase in collateral flow and the high prevalence of coronary steal during stress underscore the functional limitation of collaterals in CTOs without prior Q-wave MI. Even presumably 'well-collateralized' CTOs may benefit from a revascularization.