Randomized Trial of Primary PCI with or without RoutineManual Thrombectomy

During primary percutaneous coronary intervention (PCI), manual thrombectomymay reduce distal embolization and thus improve microvascular perfusion. Smalltrials have suggested that thrombectomy improves surrogate and clinical outcomes,but a larger trial has reported conflicting results.MethodsWe randomly assigned 10,732 patients with ST-segment elevation myocardial infarction(STEMI) undergoing primary PCI to a strategy of routine upfront manualthrombectomy versus PCI alone. The primary outcome was a composite of deathfrom cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, orNew York Heart Association (NYHA) class IV heart failure within 180 days. The keysafety outcome was stroke within 30 days.ResultsThe primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomygroup versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in thethrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.86). Therates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone;hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P = 0.34) and the primary outcome plusstent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio,1.00; 95% CI, 0.89 to 1.14; P = 0.95) were also similar. Stroke within 30 days occurredin 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%)in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P = 0.02).ConclusionsIn patients with STEMI who were undergoing primary PCI, routine manual thrombectomy,as compared with PCI alone, did not reduce the risk of cardiovasculardeath, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heartfailure within 180 days but was associated with an increased rate of stroke within30 days. (Funded by Medtronic and the Canadian Institutes of Health Research;TOTAL ClinicalTrials.gov number, NCT01149044.

[Antibiotic prophylaxis in urology]. / Antibiotikaprophylaxe in der Urologie.

The aim of perioperative antibiotic prophylaxis is the prevention of surgical site infections and urinary tract infections during urological procedures. The indication for antibiotic prophylaxis comprises several risk factors such as the degree of contamination of the operative site, duration of surgery, implantation of devices and comorbidities of the individual patient. In general this involves a single antibiotic administration before the operative procedure. The antibiotic prophylaxis is part of the total antibiotic consumption and thus a factor contributing to emergence of antibiotic resistance. It is not a substitute for hygiene measures or operative precision.

Echocardiography versus intracardiac electrocardiography-based optimization for cardiac resynchronization therapy : a comparative clinical long-term trial.

BACKGROUND: Optimization of AV and VV delay programming has been shown to be essential for the success of cardiac resynchronization therapy (CRT). Acute hemodynamic improvement can be obtained by intracardiac electrocardiogram (IEGM)-based optimization. The aim of the present study was to evaluate whether this IEGM-based algorithm is comparable to the current gold standard of echocardiography. METHODS: After device implantation patients with standard criteria for CRT, AV and VV delay programming was either optimized by an IEGM-based algorithm (IEGM group, n = 24) or by echocardiography (echo group, n = 24). Cardiopulmonary exercise capacity was assessed after 3 and 12 months on the basis of NYHA class and the 6-min-walk test. Left ventricular ejection fraction was evaluated by echocardiography. RESULTS: In both groups there was a significant decrease in NYHA class and a significant increase in 6-min-walk distance and ejection fraction after 3 and 12 months. After 12 months there was no significant difference in the proportion of responders, NYHA class and 6-min-walk distance between the IEGM the echo group. CONCLUSION: The present data show that a sustained improvement of cardiopulmonary exercise capacity can be obtained by optimizing CRT patients on the basis of an IEGM algorithm. The comparable results for cardiopulmonary exercise parameters suggest that this new method might become an important tool for adjusting CRT programming in daily practice.

[Therapy and prophylaxis of infective endocarditis]. / Therapie und Prophylaxe der infektiösen Endokarditis.

Infective endocarditis is an infection of cardiovascular structures which is typically caused by bacteria. Despite recent medical advances mortality ranges from 20 to 25%. Without treatment, IE is a lethal disease. The mortality rate depends on several clinical factors including the causative microorganism, the time of diagnosis, and the initiation of an adequate therapeutic regimen. The diagnosis is based on positive blood culture results with identical microorganisms and the demonstration of endocardial involvement. Negative blood cultures represent a diagnostic challenge which may increase the importance of diagnostic tools such as serology and PCR. An early and targeted initiation of an antibiotic therapy after microbiologic testing is crucial for therapeutic success. The immediate cooperation of Cardiologists, Microbiologists, Infectious Disease Specialists and Cardiac Surgeons is highly recommended to allow an adequate medical and surgical treatment in complex cases.Prophylaxis appears reasonable due to the inherent high mortality. The efficacy of an antibiotic prophylaxis is, nevertheless, not rigorously proven. Even if a high efficacy is assumed, the number needed to treat is extremely high due to the low individual risk. Thus, current guidelines recommend an antibiotic prophylaxis only in patients with a high risk for an adverse outcome.

Future strategies for treating Staphylococcus aureus bloodstream infections.

Bloodstream infections are potentially life-threatening diseases. They can cause serious secondary infections, such as infective endocarditis and osteomyelitis, and may result in severe sepsis. One of the most critical determinants of survival is the induction of timely and effective antibiotic therapy. One of the leading causes of bloodstream infections is Staphylococcus aureus, with an increasing proportion of isolates being resistant to methicillin. Methicillin-resistant S. aureus (MRSA) is associated with greater morbidity and mortality rates than methicillin-sensitive S. aureus (MSSA). Standard-of-care antibiotic treatments for S. aureus bloodstream infections are limited by toxicity and/or differential efficacy against MRSA and MSSA, which makes the choice of empirical therapy difficult. New management strategies are required to address the challenges raised by S. aureus bloodstream infections and MRSA in particular. These may include the use of techniques that allow the early identification of complications arising from S. aureus bacteraemia, rapid pathogen identification to enable the administration of appropriate antibiotic therapy, and the identification of new drugs with novel modes of action that may circumvent antibiotic resistance and enable effective empirical treatment of both MSSA and MRSA infections.

Resistant hypertension in patients with chronic aortic dissection.

Strict blood pressure control is pivotal in the management of patients with aortic dissection (AD), but is frequently difficult to achieve. We determined antihypertensive medical therapy and levels of blood pressure (BP) control in 40 patients with chronic AD. Patient charts were reviewed for clinical variables, serial BP measurements, and antihypertensive drug therapy. Patients were divided into two groups: patients in group 1 had effective BP control (<135/80 mmHg), patients in group 2 had resistant hypertension (BP>/=135/80 mmHg despite prescription of at least three antihypertensive drugs). Overall, systolic BP (SBP) was 130+/-20 mmHg, and diastolic BP (DBP) was 72+/-13 mmHg. Patients received a median of 4 (1-6) antihypertensive drugs. beta-blockers were used in 38/40 (95%) patients. Effective BP control was achieved in 24/40 (60%) patients (group 1), while 16/40 (40%) patients had resistant hypertension (group 2) despite receiving significantly more antihypertensive drugs (5 [4-6] vs 4 [1-5], P=0.001). Mean SBP was 116+/-9 (101-132) mmHg in group 1 and 151+/-13 (137-181) mmHg in group 2 (P<0.001); there was no difference in DBP. Group 2 patients had a significantly higher body mass index and were younger than patients in group 1. In conclusion, in the majority of patients with chronic AD, effective BP control can be achieved, but usually requires the combination of multiple antihypertensive drugs. However, in a significant proportion of patients (40%), who appear to be younger and more obese, medical therapy fails to achieve effective BP control despite use of a multiple drug regimen.

Genetics of human arterial hypertension.

Arterial hypertension is one of the major cardiovascular risk factors in Western countries. Besides some well established, but rather rare forms of secondary hypertension, essential hypertension is the most common diagnosis. The hereditary nature of this disease has been well established in many familial studies. The quantitative contribution of genetic factors to blood pressure variance is estimated to be about 30%, however, the genetic background of essential hypertension is complex and currently not fully understood. Besides few monogenetic forms of Mendelian transmitted hypertension, current efforts are usually directed at the identification of single contributing genetic factors. This review is thought to highlight current strategies towards a better understanding of the genetic background of essential hypertension with particular respect to genetic variants of the renin-angiotensin system, of signaling pathways such as heterotrimeric G-proteins and alpha-adducin. Moreover, genetic association studies often fail to replicate findings from previous studies. This may be in part due to the polygenetic nature of the disease. Another potential reason may be the diversity of the investigated populations. The current results of genetic analyses of essential hypertension highlight, thus, the need for a more differentiated approach to the understanding of complex, polygenetic traits implementing gene-gene-, and gene-environment interactions or distinguished functional testing of thoroughly phenotyped cohorts under standardised environmental conditions.

Genetics of human coronary vasomotion.

While the number of genetic polymorphisms associated with cardiovascular diseases rapidly increases, the functional implications of such gene alterations are often poorly understood. Moreover, findings from genetic association studies are often contradictory, which limits the common acceptance of a role of these genetic variants in human disease. One effective approach towards a better understanding of the pathophysiologic relevance of a gene variant is the description of its impact on dynamic or functional phenotypes such as coronary vasomotor responses to exogenous or endogenous stimuli. This brief review focuses on the impact of variants in genes of the renin-angiotensin system, the alpha2-adrenoceptor gene, and the G protein beta3 subunit gene on coronary vasomotor responses.

[S2 guideline for infectious endocarditis]. / S2 Leitlinie zur Diagnostik und Therapie der infektiösen Endokarditis. Finale Version 5.0 08/2004.

Microbe-induced (infectious) endocarditis is an endovascular infection, caused mainly by bacteria, of cardiovascular structures. The major predilection site are the native heart valves, but involvement of implanted intracardiac foreign material is increasingly being seen. The mortality rate of infectious endocarditis depends on clinical factors and the causal agent, but also on the time of the establishment of the diagnosis and the initiation of appropriate treatment. In Germany, the current mortality rate ranges up to 18%. Between January 2003 and July 2004, with the aim of improving patient care and thus the outcome of this condition, a guideline commission worked out recommendations for the diagnosis, treatment and management of the disease for the use of general practitioners and hospital physicians, in particular microbiologists, infectiologists, cardiologists and cardiac surgeons. The basis for this guideline was the systematic search through the literature of the European guideline. On the 16th and 28th of June 2004, the entire guideline was formerly approved in a nominal group process.

[Brachytherapy after coronary interventions: current state and future perspectives]. / Brachytherapie nach koronaren Interventionen: aktueller Stand und Zukunftsperspektiven.

Intracoronary brachytherapy is a novel, meanwhile established therapy. It is currently the only interventional procedure which has proven to effectively reduce the restenosis rates after intervention of long and diffuse in-stent restenosis. For this indication, brachytherapy can be regarded as the current treatment of choice. Randomized studies yield promising results for bypass interventions or interventions in small vessels or diabetic patients. These findings may encourage the decision to perform a percutaneous, transluminal intervention in such high-risk patients. In clinical practice, implantation of new stents in combination with brachytherapy procedures should be avoided as far as possible. In any case, the combined antiaggregatory therapy should be conducted sufficiently long to minimize the danger of late stent thrombosis. Under this treatment, the expected thrombosis rates ar within the range of placebo-treated patients. The length of the radiation source should be sufficient to cover the entire interventional injury length to avoid recurrent edge stenosis. De novo lesions are currently not a routine indication for intracoronary brachytherapy. Although intracoronary brachytherapy may effectively reduce restenosis rates in sufficiently irradiated de novo lesion segments, de novo lesions should be treated only within the set-up of controlled studies. The current available data with a follow-up period of up to 5 years show that intracoronary brachytherapy is also in the mid-term a safe and effective therapy for the reduction of restenosis after coronary interventions.

Urinary excretion and bactericidal activities of gemifloxacin and ofloxacin after a single oral dose in healthy volunteers.

In a randomized crossover study, 16 volunteers (8 men, 8 women) received single oral doses of 320 mg of gemifloxacin and 400 mg of ofloxacin on two separate occasions in the fasting state to assess the urinary excretion and urinary bactericidal titers (UBTs) at intervals for up to 144 h. Ofloxacin showed higher concentrations in urine compared with those of gemifloxacin. The median (range) cumulative excretion of gemifloxacin was 29.7% (8.4 to 48.7%) of the parent drug administered, and median (range) cumulative excretion of ofloxacin was 84.3% (46.5 to 95.2%) of the parent drug administered. The UBTs, i.e., the highest twofold dilutions (with antibiotic-free urine as the diluent) of urine that were still bactericidal, were determined for a reference strain and nine uropathogens for which the MICs of gemifloxacin and ofloxacin were as follows: Escherichia coli ATCC 25922, 0.016 and 0.06 microg/ml, respectively; Klebsiella pneumoniae, 0.03 and 0.06 microg/ml, respectively; Proteus mirabilis, 0.125 and 0.125 microg/ml, respectively; Escherichia coli, 0.06 and 0.5 microg/ml, respectively; Pseudomonas aeruginosa, 1 and 4 microg/ml, respectively; Staphylococcus aureus, 0.008 and 0.25 microg/ml, respectively; Enterococcus faecalis, 0.06 and 2 microg/ml, respectively; Staphylococcus aureus, 0.25 and 4 microg/ml, respectively; Enterococcus faecalis, 0.5 and 32 microg/ml, respectively; and Staphylococcus aureus, 2 and 32 microg/ml, respectively. Generally, the UBTs for gram-positive uropathogens were higher for gemifloxacin than for ofloxacin and the UBTs for gram-negative uropathogens were higher for ofloxacin than for gemifloxacin. According to the UBTs, ofloxacin-resistant uropathogens (MICs, >or=4 mg/liter) should also be considered gemifloxacin resistant. Although clinical trials have shown that gemifloxacin is effective for the treatment of uncomplicated urinary tract infections, whether an oral dosage of 320 mg of gemifloxacin once daily is also adequate for the treatment of complicated urinary tract infections has yet to be confirmed.

[Diagnosis of endocarditis today: Duke criteria or clinical judgment?]. / Endokarditisdiagnostik heute: Duke-Kriterien oder klinische Einschätzung?

DIAGNOSIS OF INFECTIVE ENDOCARDITIS: Due to the complexity of the clinical diagnosis of infective endocarditis, standardized diagnostic schemes have been developed to improve the sensitivity and specificity of the diagnosis. The Von Reyn criteria, introduced in 1981 relied mainly on clinical, microbiological, and histopathological criteria and were for more than 10 years regarded as the diagnostic goldstandard. However, the Von Reyn criteria have a sensitivity of merely about 30-60% and their reliability is especially low in case of negative blood cultures. ROLE OF ECHOCARDIOGRAPHY: An important step towards an improved sensitivity and specificity in the diagnosis of infective endocarditis was the introduction of transesophageal echocardiography, which is far more sensitive and specific in this indication than the transthoracic approach. Besides the early detection of vegetations and complications such as abscess formation, valvular destructions or perforations, echocardiography may be helpful to identify patients at risk for a prolonged healing, embolization, or may be also used to monitor the therapeutic progress. THE DUKE CRITERIA: Implementation of echocardiography into the Duke criteria, introduced in 1994, yielded as expected, a significant higher sensitivity of up to 100% than the von Reyn criteria with an almost identical specificity. Thus, the latter were completely replaced by the Duke criteria in clinical practice. MODIFICATIONS OF THE DUKE CRITERIA: Nevertheless, some uncertainty remains, especially in culture-negative endocarditis which has led to certain modifications of the Duke criteria. Besides the implementation of unspecific inflammatory parameters such as the C-reactive protein, a positive Q-fever serology has been added and any S. aureus bacteremia is now judged as major criterion. Although a prospective evaluation has to be awaited, these modifications appear promising and should be implemented into clinical practice. CONCLUSIONS: The Duke criteria are currently the most sensitive tool in the diagnosis of infective endocarditis. It can be expected that they will help to significantly shorten the time to diagnosis, and may, thus, improve the clinical outcome.

eNOS 894T allele and coronary blood flow at rest and during adenosine-induced hyperemia.

The 894T allele of a G894T polymorphism in the endothelial nitric oxide synthase (eNOS) gene is associated with decreased eNOS activity, cleavage of the protein, and endothelial dysfunction. The present study evaluated the association with coronary blood flow (CBF) at rest and during adenosine (ADO)-induced hyperemia. CBF was determined by Doppler flow wire and angiography in 97 left anterior descending arteries of individuals without coronary artery disease. At rest, average peak velocity (APV) was lower and coronary vascular resistance (CVR) was higher in homozygous carriers of the 894T allele than in heterozygotes and individuals without the 894T allele. CBF tended to be lower in eNOS 894T allele carriers. During ADO-induced hyperemia (18 microg ic), APV, CVR, and CBF were not statistically different between the genotypes. The reduced APV at rest in conjunction with an increased CVR indicates a vasomotor dysfunction related to an increased microvascular resting tone in eNOS 894T allele carriers.

Early clinical experience with the 6 French Angio-Seal device: immediate closure of femoral puncture sites after diagnostic and interventional coronary procedures.

The objective of this study was to assess the early safety and efficacy of the novel 6 Fr Angio-Seal device for routine clinical use after diagnostic cardiac catheterization and coronary angioplasty. In a prospective study, we used the 6 Fr Angio-Seal device in 180 consecutive patients (131 male, 49 female, mean age 60.7 years) for closure of femoral arterial puncture sites immediately after diagnostic (n = 108) or interventional (n = 72) coronary procedures independent of the coagulation status. All patients were monitored for 24 hr after the procedure and followed for 30 days. The closure device was successfully deployed in 95.4% after diagnostic catheterization versus 98.6% after coronary angioplasty (P = 0.963). Immediate hemostasis was achieved in 91.5% versus 90.1% of the patients (P = 0.993). Major complications were observed 1.9% versus 2.8% of the patients (P = 0.885). During 30-day follow-up, no late events or complications were reported. The 6 Fr Angio-Seal device is a safe and effective device that allows for immediate closure of femoral puncture sites after both diagnostic and interventional procedures with a low rate of major complications.