[Cardiogenic shock complicating myocardial infarction]. / Infarktbedingter kardiogener Schock.

Cardiogenic shock as a complication of myocardial infarction (5-10%) increases the mortality of uncomplicated myocardial infarction from less than 10% to 40%. This is due to the development of multiple organ dysfunction syndrome triggered by the extensive shock-induced impairment of organ perfusion. Therefore, guideline-based treatment should not only be restricted to reopening of the occluded coronary artery and management of complications of the infarction: important for survival are also guideline-driven optimization of organ perfusion by inotropic and vasoactive substances and, with well-defined indications, by temporary mechanical circulatory support but not by intra-aortic counterpulsation. Equally important, however, are shock-specific intensive care measures to prevent or attenuate organ dysfunction, such as lung protective ventilation in cases where ventilation is obligatory.

Transcoronary pacing in an animal model : Second coated guidewire versus cutaneous patch as indifferent electrodes.

BACKGROUND: Transcoronary pacing is a seldom used treatment option for unheralded bradycardias in the setting of percutaneous coronary interventions (PCI). In the present study we compared a coated guidewire inserted proximally into a coronary artery with a cutaneous patch electrode as indifferent electrodes for transcoronary pacing in a porcine model. METHODS: Transcoronary pacing was investigated in 7 adult pigs in an animal catheterization laboratory. A standard guidewire insulated by a monorail-balloon was advanced into the periphery of a coronary artery serving as the cathode. As the indifferent anode, a special guidewire with electrical insulated by a polytetrafluoroethylene (PTFE) coating was positioned into the proximal part of the same coronary vessel. Transcoronary pacing parameters (threshold and impedance data and the magnitude of the epicardial electrogram) were compared with unipolar transcoronary pacing using a cutaneous patch electrode. RESULTS: Transcoronary pacing was successful against both indifferent electrodes. Pacing thresholds obtained with the coated guidewire technique (1.8 ± 1.3 V) were similar to those obtained by standard unipolar transcoronary pacing with a cutaneous patch electrode (1.8 ± 1.5 V). The impedance with the additional coated guidewire was 419 ± 144 Ω and thereby slightly higher compared to 320 ± 103 Ω obtained by pacing against the patch electrode (p < 0.05). Both settings yielded comparable R­wave amplitudes (8.0 ± 5.1 mV vs. 7.1 ± 3.6 mV). CONCLUSIONS: A second coated guidewire is as effective as a cutaneous patch electrode when added as an indifferent electrode in transcoronary pacing. This transcoronary pacing technique could replace temporary transvenous pacing in emergency situations during PCI, especially when using the radial approach.

Mortality and morbidity 1 year after stopping a remote patient management intervention: extended follow-up results from the telemedical interventional management in patients with heart failure II (TIM-HF2) randomised trial.

BACKGROUND: The Telemedical Interventional Management in Heart Failure II (TIM-HF2) trial showed that, compared with usual care, a structured remote patient management (RPM) intervention done over 12-months reduced the percentage of days lost due to unplanned cardiovascular hospitalisations and all-cause death. The aim of the study was to evaluate whether this clinical benefit seen for the RPM group during the initial 12 month follow-up of the TIM-HF2 trial would be sustained 1 year after stopping the RPM intervention. METHODS: TIM-HF2 was a prospective, randomised, multicentre trial done in 43 hospitals, 60 cardiology practices, and 87 general practitioners in Germany. Patients with heart failure, New York Heart Association functional class II or III, and who had been hospitalised for heart failure within 12 months before randomisation were randomly assigned to either the RPM intervention or usual care. At the final study visit (main trial), the RPM intervention was stopped and the 1 year extended follow-up period started, which lasted 1 year. The primary outcome was percentage of days lost due to unplanned cardiovascular hospitalisations and all-cause mortality. Analyses were done using the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01878630. FINDINGS: Between Aug 13, 2013, and May 12, 2017, 1538 patients were enrolled (765 to the remote patient management group and 773 to the usual care group) in the main trial. 671 of 765 patients in the remote patient management group and 673 of 773 in the usual care group completed the main trial and started the extended follow-up period up to 1 year later. In the extended follow-up period, the percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause mortality did not differ significantly between groups weighted mean 5·95% [95% CI 4·59-7·31] in the RPM group vs 6·64% [95% CI 5·19-8·08] in the usual care group [rate ratio 0·79; 95% CI 0·78-1·21]). However, when data from the main trial and the extended follow-up period were combined, the percentage of days lost due to unplanned cardiovascular hospitalisation or all-cause death was significantly less in patients allocated to the RPM group (382 [50%] of 765; weighted mean 9·28%; 95% CI 7·76-10·81) than in the UC group (398 [51%] of 773; 11·78%; 95% CI 10·08-13·49; ratio of weighted average 0·79; 95% CI 0·62-1·00; p=0·0486). INTERPRETATION: The positive effect of our RPM intervention on morbidity and mortality over the course of the main trial was no longer observed 1 year after stopping the RPM intervention. However, because the TIM-HF2 trial was not powered to show significance during the extended follow-up period, our results are exploratory and require further research. FUNDING: German Federal Ministry of Education and Research.

Use, Persistence, Efficacy, and Safety of Apixaban in Patients with Non-Valvular Atrial Fibrillation in Unselected Patients in Germany. Results of the Prospective Apixaban in Atrial Fibrillation (APAF) Registry.

INTRODUCTION: Apixaban has been shown to be superior to warfarin in patients with non-valvular atrial fibrillation in the randomized ARISTOTLE trial and its use is recommended in current guidelines. There are only scarce data about its use, efficacy, and safety in unselected patients in Germany. METHODS AND RESULTS: The APAF registry is a prospective non-interventional study enrolling 5015 patients with non-valvular atrial fibrillation. Of these, 1349 (26.9%) patients were initially treated with apixaban and followed up at 3 and 12 months. The dose of apixaban used was 1 × 2.5 mg in 1.6%, 2 × 2.5 mg in 30.4%, and 2 × 5 mg daily in 68.0% of patients, respectively. Inappropriate underdosing of apixaban was observed in 22.3%, mostly in elderly patients with higher HAS-BLED Score and a history of bleeding. Persistence to apixaban after 1 year was 88.6%, while the dose was changed in 3.7% of patients. Switching to other NOACs or VKAs occurred in 5.1%. After 12 months, all-cause mortality was 5.0%, non-fatal stroke occurred in 0.4%, non-fatal myocardial infarction in 0.6%, ISTH major bleeding in 0.8%, moderate or minor bleeding in 4.3% of patients, respectively. CONCLUSIONS: In this prospective experience in unselected patients with atrial fibrillation, persistence to apixaban was high, and efficacy and safety were comparable to the results in clinical trials, supporting its use in clinical practice.

Efficacy of telemedical interventional management in patients with heart failure (TIM-HF2): a randomised, controlled, parallel-group, unmasked trial.

BACKGROUND: Remote patient management in patients with heart failure might help to detect early signs and symptoms of cardiac decompensation, thus enabling a prompt initiation of the appropriate treatment and care before a full manifestation of a heart failure decompensation. We aimed to investigate the efficacy of our remote patient management intervention on mortality and morbidity in a well defined heart failure population. METHODS: The Telemedical Interventional Management in Heart Failure II (TIM-HF2) trial was a prospective, randomised, controlled, parallel-group, unmasked (with randomisation concealment), multicentre trial with pragmatic elements introduced for data collection. The trial was done in Germany, and patients were recruited from hospitals and cardiology practices. Eligible patients had heart failure, were in New York Heart Association class II or III, had been admitted to hospital for heart failure within 12 months before randomisation, and had a left ventricular ejection fraction (LVEF) of 45% or lower (or if higher than 45%, oral diuretics were being prescribed). Patients with major depression were excluded. Patients were randomly assigned (1:1) using a secure web-based system to either remote patient management plus usual care or to usual care only and were followed up for a maximum of 393 days. The primary outcome was percentage of days lost due to unplanned cardiovascular hospital admissions or all-cause death, analysed in the full analysis set. Key secondary outcomes were all-cause and cardiovascular mortality. This study is registered with ClinicalTrials.gov, number NCT01878630, and has now been completed. FINDINGS: Between Aug 13, 2013, and May 12, 2017, 1571 patients were randomly assigned to remote patient management (n=796) or usual care (n=775). Of these 1571 patients, 765 in the remote patient management group and 773 in the usual care group started their assigned care, and were included in the full analysis set. The percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause death was 4·88% (95% CI 4·55-5·23) in the remote patient management group and 6·64% (6·19-7·13) in the usual care group (ratio 0·80, 95% CI 0·65-1·00; p=0·0460). Patients assigned to remote patient management lost a mean of 17·8 days (95% CI 16·6-19·1) per year compared with 24·2 days (22·6-26·0) per year for patients assigned to usual care. The all-cause death rate was 7·86 (95% CI 6·14-10·10) per 100 person-years of follow-up in the remote patient management group compared with 11·34 (9·21-13·95) per 100 person-years of follow-up in the usual care group (hazard ratio [HR] 0·70, 95% CI 0·50-0·96; p=0·0280). Cardiovascular mortality was not significantly different between the two groups (HR 0·671, 95% CI 0·45-1·01; p=0·0560). INTERPRETATION: The TIM-HF2 trial suggests that a structured remote patient management intervention, when used in a well defined heart failure population, could reduce the percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause mortality. FUNDING: German Federal Ministry of Education and Research.

Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndrome.

BACKGROUND: Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) as complications of acute myocardial infarction (AMI), heart failure (HF) or cardiac surgery are life-threatening conditions. While there is a broad body of evidence for the treatment of people with acute coronary syndrome under stable haemodynamic conditions, the treatment strategies for people who become haemodynamically unstable or develop CS remain less clear. We have therefore summarised here the evidence on the treatment of people with CS or LCOS with different inotropic agents and vasodilative drugs. This is the first update of a Cochrane review originally published in 2014. OBJECTIVES: To assess efficacy and safety of cardiac care with positive inotropic agents and vasodilator strategies in people with CS or LCOS due to AMI, HF or cardiac surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CPCI-S Web of Science in June 2017. We also searched four registers of ongoing trials and scanned reference lists and contacted experts in the field to obtain further information. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials in people with myocardial infarction, heart failure or cardiac surgery complicated by cardiogenic shock or LCOS. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified 13 eligible studies with 2001 participants (mean or median age range 58 to 73 years) and two ongoing studies. We categorised studies into eight comparisons, all against cardiac care and additional other active drugs or placebo. These comparisons investigated the efficacy of levosimendan versus dobutamine, enoximone or placebo, epinephrine versus norepinephrine-dobutamine, amrinone versus dobutamine, dopexamine versus dopamine, enoximone versus dopamine and nitric oxide versus placebo.All trials were published in peer-reviewed journals, and analysis was done by the intention-to-treat (ITT) principle. Twelve of 13 trials were small with few included participants. Acknowledgement of funding by the pharmaceutical industry or missing conflict of interest statements emerged in five of 13 trials. In general, confidence in the results of analysed studies was reduced due to serious study limitations, very serious imprecision or indirectness. Domains of concern, which show a high risk of more than 50%, include performance bias (blinding of participants and personnel) and bias affecting the quality of evidence on adverse events.Levosimendan may reduce short-term mortality compared to a therapy with dobutamine (RR 0.60, 95% CI 0.37 to 0.95; 6 studies; 1776 participants; low-quality evidence; NNT: 16 (patients with moderate risk), NNT: 5 (patients with CS)). This initial short-term survival benefit with levosimendan vs. dobutamine is not confirmed on long-term follow up. There is uncertainty (due to lack of statistical power) as to the effect of levosimendan compared to therapy with placebo (RR 0.48, 95% CI 0.12 to 1.94; 2 studies; 55 participants, very low-quality evidence) or enoximone (RR 0.50, 95% CI 0.22 to 1.14; 1 study; 32 participants, very low-quality evidence).All comparisons comparing other positive inotropic, inodilative or vasodilative drugs presented uncertainty on their effect on short-term mortality with very low-quality evidence and based on only one RCT. These single studies compared epinephrine with norepinephrine-dobutamine (RR 1.25, 95% CI 0.41 to 3.77; 30 participants), amrinone with dobutamine (RR 0.33, 95% CI 0.04 to 2.85; 30 participants), dopexamine with dopamine (no in-hospital deaths from 70 participants), enoximone with dobutamine (two deaths from 40 participants) and nitric oxide with placebo (one death from three participants). AUTHORS' CONCLUSIONS: Apart from low quality of evidence data suggesting a short-term mortality benefit of levosimendan compared with dobutamine, at present there are no robust and convincing data to support a distinct inotropic or vasodilator drug-based therapy as a superior solution to reduce mortality in haemodynamically unstable people with cardiogenic shock or LCOS.Considering the limited evidence derived from the present data due to a generally high risk of bias and imprecision, it should be emphasised that there remains a great need for large, well-designed randomised trials on this topic to close the gap between daily practice in critical care medicine and the available evidence. It seems to be useful to apply the concept of 'early goal-directed therapy' in cardiogenic shock and LCOS with early haemodynamic stabilisation within predefined timelines. Future clinical trials should therefore investigate whether such a therapeutic concept would influence survival rates much more than looking for the 'best' drug for haemodynamic support.

Optimal course of treatment in acute cardiogenic shock complicating myocardial infarction.

INTRODUCTION: About 5% of patients with myocardial infarction suffer from cardiogenic shock as a complication, with a mortality of ≥30%. Primary percutaneous coronary intervention as soon as possible is the most successful therapeutic approach. Prognosis depends not only on the extent of infarction, but also - and even more - on organ hypoperfusion with consequent development of multiple organ dysfunction syndrome. Areas covered: This review covers diagnostic, monitoring and treatment concepts relevant for caring patients with cardiogenic shock complicating myocardial infarction. All major clinical trials have been selected for review of the recent data. Expert commentary: For optimal care, not only primary percutaneous intervention of the occluded coronary artery is necessary, but also best intensive care medicine avoiding the development of multiple organ dysfunction syndrome and finally death. On contrary, intra-aortic balloon pump - though used for decades - is unable to reduce mortality of patients with cardiogenic shock complicating myocardial infarction.

Effect of inflammatory mediators on cardiovascular function.

PURPOSE OF REVIEW: Inflammatory mediators can interfere with cardiovascular system. This article describes some recent findings in this field. RECENT FINDINGS: In septic cardiomyopathy, direct and indirect interactions of endotoxin with the pacemaker current contribute to cardiac autonomic dysfunction and inadequately high heart rate, worsening prognosis. In myocardial infarction, inflammatory blood cells correlate with impaired coronary microvascular reperfusion. In cardiogenic shock, systemic inflammation and development of multiorgan dysfunction syndrome have a major impact on mortality. Shock patients have low levels of activated protein C and high levels of the endogenous danger signal molecule peroxiredoxin 1; both conditions might represent further therapeutic targets. As major cause of cytopathic hypoxia, mitochondrial dysfunction has also been identified in mitochondria from peripheral blood mononuclear cells in paediatric septic shock. Transcatheter aortic valve endocarditis, a new endocarditis entity after transcatheter aortic valve implantation in old and very old patients, needs our special attention, because immunosenescence may modify the clinical course in a negative sense. Systemic spreading of endocarditis to septic shock adds to the local valve infection the problem of septic shock. SUMMARY: Not only in septic shock, but also in classic heart diseases like cardiogenic shock and endocarditis, the detrimental role of inflammatory mediators becomes more and more evident, whereas effective anti-inflammatory treatment concepts are still missing.

Improving Treatment Adherence in Heart Failure.

BACKGROUND: Despite improved treatment options, heart failure remains the third most common cause of death in Germany and the most common reason for hospitalization. The treatment recommendations contained in the relevant guidelines have been incompletely applied in practice. The goal of this systematic review is to study the efficacy of adherence-promoting interventions for patients with heart failure with respect to the taking of medications, the implementation of recommended lifestyle changes, and the improvement in clinical endpoints. METHODS: We performed a meta-analysis of pertinent publications retrieved by a systematic literature search. RESULTS: 55 randomized controlled trials were identified, in which a wide variety of interventions were carried out on heterogeneous patient groups with varying definitions of adherence. These trials included a total of 15 016 patients with heart failure who were cared for as either inpatients or outpatients. The efficacy of interventions to promote adherence to drug treatment was studied in 24 trials; these trials documented improved adherence in 10% of the patients overall (95% confidence interval [CI]: [5; 15]). The efficacy of interventions to promote adherence to lifestyle recommendations was studied in 42 trials; improved adherence was found in 31 trials. Improved adherence to at least one recommendation yielded a long-term absolute reduction in mortality of 2% (95% CI: [0; 4]) and a 10% reduction in the likelihood of hospitalization within 12 months of the start of the intervention (95% CI: [3; 17]). CONCLUSION: Many effective interventions are available that can lead to sustained improvement in patient adherence and in clinical endpoints. Longterm success depends on patients' assuming responsibility for their own health and can be achieved with the aid of coordinated measures such as patient education and regular follow-up contacts.

[Update cardiogenic shock]. / Update kardiogener Schock.

Although IABP support induces left ventricular unloading, these beneficial effect does not lead to improved microcirculation and survival. The use of percutaneous extracorporeal support systems (ECLS, ECMO) as well as left ventricular assist devices (pVAD) for adjunctive treatment of STEMI has increased during the recent years, but without sufficient evidence for a survival benefit. The PCI-access via the radial artery may lead to improved outcomes, especially in regard to survival. A liberal transfusion regimen for red cell packages in the perioperative phase of cardiac surgery seems to improve outcomes in regard to lower incidence of cardiogenic shock postoperatively.

Takotsubo Cardiomyopathy: What we have Learned in the Last 25 Years? (A Comparative Literature Review).

We performed a comparative literature review, to elucidate the major features of the Takotsubo (stress) cardiomyopathy (TCM) collected in last 25 years. TCM is characterized by left- or biventricular apical ballooning with a clinical presentation, electrocardiographic abnormalities, and biomarker profils similar to those seen in acute myocardial infarction. Epidemiological studies have shown that TCM is more common in postmenopausal women; however exact figures are not available. The underlying aetiology is still largely undetermined. Elevated catecholamine levels, lack of estrogen, disturbed myocardial fatty acid metabolism and plaque rupture with spontaneous thrombolysis are potentially discussed mechanisms responsible for inducing a prolonged stunned myocardium. Strong emotional or physical stress is the most frequently described trigger in the literature. Therapy recommendations include appropriate antiplatelet treatment, ß-blockers and ACE inhibitors. The abnormal kinetics usually resolve or improve within a month and carry a favorable prognosis in most cases. However, all the suspected complications of an acute myocardial infarction, including cardiogenic shock or lethal arrhythmias, may still occur.

Intra-aortic balloon pump counterpulsation (IABP) for myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Intra-aortic balloon pump counterpulsation (IABP) is currently the most commonly used mechanical assist device for patients with cardiogenic shock due to acute myocardial infarction. Although there has been only limited evidence from randomised controlled trials, the previous guidelines of the American Heart Association/American College of Cardiology (AHA/ACC) and the European Society of Cardiology (ESC) strongly recommended the use of the IABP in patients with infarction-related cardiogenic shock on the basis of pathophysiological considerations, non-randomised trials and registry data. The recent guidelines downgraded the recommendation based on a meta-analysis which could only include non-randomised trials showing conflicting results. Up to now, there have been no guideline recommendations and no actual meta-analysis including the results of the large randomised multicentre IABP-SHOCK II Trial which showed no survival benefit with IABP support. This systematic review is an update of the review published in 2011. OBJECTIVES: To evaluate, in terms of efficacy and safety, the effect of IABP versus non-IABP or other assist devices guideline compliant standard therapy on mortality and morbidity in patients with acute myocardial infarction complicated by cardiogenic shock. SEARCH METHODS: Searches of CENTRAL, MEDLINE (Ovid) and EMBASE (Ovid), LILACS, IndMed and KoreaMed, registers of ongoing trials and proceedings of conferences were updated in October 2013. Reference lists were scanned and experts in the field contacted to obtain further information. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials on patients with acute myocardial infarction complicated by cardiogenic shock. DATA COLLECTION AND ANALYSIS: Data collection and analysis were performed according to the published protocol. Individual patient data were provided for six trials and merged with aggregate data. Summary statistics for the primary endpoints were hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS: Seven eligible studies were identified from a total of 2314 references. One new study with 600 patients was added to the original review. Four trials compared IABP to standard treatment and three to other percutaneous left assist devices (LVAD). Data from a total of 790 patients with acute myocardial infarction and cardiogenic shock were included in the updated meta-analysis: 406 patients were treated with IABP and 384 patients served as controls; 339 patients were treated without assisting devices and 45 patients with other LVAD. The HR for all-cause 30-day mortality of 0.95 (95% CI 0.76 to 1.19) provided no evidence for a survival benefit. Different non-fatal cardiovascular events were reported in five trials. During hospitalisation, 11 and 4 out of 364 patients from the intervention groups suffered from reinfarction or stroke, respectively. Altogether 5 out of 363 patients from the control group suffered from reinfarction or stroke. Reocclusion was treated with subsequent re-revascularization in 6 out of 352 patients from the intervention group and 13 out of 353 patients of the control group. The high incidence of complications such as moderate and severe bleeding or infection in the control groups has to be attributed to interventions with other LVAD. Possible reasons for bias were more frequent in small studies with high cross-over rates, early stopping and the inclusion of patients with IABP at randomisation. AUTHORS' CONCLUSIONS: Available evidence suggests that IABP may have a beneficial effect on some haemodynamic parameters. However, this did not result in survival benefits so there is no convincing randomised data to support the use of IABP in infarct-related cardiogenic shock.

Transcoronary mapping of ventricular asynchrony due to left bundle branch block in a porcine model.

BACKGROUND: Optimal positioning of the left ventricular (LV) lead at the latest activated part of the left ventricle is one of the major challenges in implantation of cardiac resynchronization therapy (CRT) devices with respect to ascertaining an optimal resynchronization effect resulting in a high responder rate. In the present study, we evaluated the feasibility of transcoronary measurement of LV electrical activation by a coated guidewire in a porcine model. METHODS AND RESULTS: Transcoronary measurement of ventricular activation was performed in 16 pigs under general anesthesia. Left bundle branch block (LBBB) was induced by transvenous pacing in the right ventricular apex (RVA). A specially coated guidewire (Vision Wire; Biotronik) serving as the different electrode was positioned subsequently in the proximal and distal part of each coronary main vessel. A cutaneous skin patch electrode was placed at the back of the thorax of the animal to act as the indifferent electrode. Both electrodes were connected to a portable electrophysiology lab system (EP Tracer 38; CardioTek). Mean QRS width during transvenous right ventricular pacing was 83 ± 5 ms with a typical LBBB pattern. The measured time interval between the beginning of the QRS complex in the surface electrocardiogram (ECG) and the local signal derived from the tip of the guidewire (QRS-EGM) was 32 ± 9 ms in the distal ramus circumflex (RCX) coronary artery and 51 ± 6 ms in the proximal RCX, yielding a mean delay of 18 ± 8 ms within this vessel. In the left anterior descending (LAD) coronary artery, the local signal was 23 ± 10 ms in the distal part and 41 ± 10 ms in the proximal part of the vessel, with an identical mean delay of 18 ± 8 ms. The QRS-EGM interval within the right coronary artery (RCA) was 14 ± 8 ms in the distal part and 40 ± 9 ms in the proximal part of the vessel, resulting in a mean delay of 25 ± 7 ms. The delay between the activation of the distal RCA and the activation of the distal LAD and RCX was statistically significant (P<.001). Within the proximal guidewire positions, the latest electrical activation of the left ventricle during pacing-induced LBBB could be observed in the RCX with 51.4 ± 6.3 ms (P<.01). CONCLUSION: Transcoronary measurement of LV excitation by a specially coated guidewire is feasible and could confirm the electrical asynchrony induced by LBBB. Since coronary angiography is a mandatory part of the evaluation of patients for CRT implantation, a "transcoronary mapping procedure" can be easily performed, thereby evaluating the latest activated part of the left ventricle in advance of the implantation procedure, aiming to improve the responder rate in CRT therapy.

Inotropic agents and vasodilator strategies for acute myocardial infarction complicated by cardiogenic shock or low cardiac output syndrome.

BACKGROUND: The recently published German-Austrian S3 Guideline for the treatment of infarct related cardiogenic shock (CS) revealed a lack of evidence for all recommended therapeutic measures. OBJECTIVES: To determine the effects in terms of efficacy, efficiency and safety of cardiac care with inotropic agents and vasodilator strategies versus placebo or against each other for haemodynamic stabilisation following surgical treatment, interventional therapy (angioplasty, stent implantation) and conservative treatment (that is no revascularization) on mortality and morbidity in patients with acute myocardial infarction (AMI) complicated by CS or low cardiac output syndrome (LCOS). SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), EMBASE (Ovid) and ISI Web of Science, registers of ongoing trials and proceedings of conferences in January 2013. Reference lists were scanned and experts in the field were contacted to obtain further information. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials in patients with AMI complicated by CS or LCOS. DATA COLLECTION AND ANALYSIS: Data collection and analysis were performed according to the published protocol. All trials were analysed individually. Hazard ratios (HRs) and odds ratios with 95% confidence intervals (CI) were extracted but not pooled because of high heterogeneity between the control group interventions. MAIN RESULTS: Four eligible, very small studies were identified from a total of 4065 references. Three trials with high overall risk of bias compared levosimendan to standard treatment (enoximone or dobutamine) or placebo. Data from a total of 63 participants were included in our comparisons, 31 were treated with levosimendan and 32 served as controls. Levosimendan showed an imprecise survival benefit in comparison with enoximone based on a very small trial with 32 participants (HR 0.33; 95% CI 0.11 to 0.97). Results from the other similarly small trials were too imprecise to provide any meaningful information about the effect of levosimendan in comparison with dobutamine or placebo. Only small differences in haemodynamics, length of hospital stay and the frequency of major adverse cardiac events or adverse events overall were found between study groups.Only one small randomised controlled trial with three participants was found for vasodilator strategies (nitric oxide gas versus placebo) in AMI complicated by CS or LCOS. This study was too small to draw any conclusions on the effects on our key outcomes. AUTHORS' CONCLUSIONS: At present there are no robust and convincing data to support a distinct inotropic or vasodilator drug based therapy as a superior solution to reduce mortality in haemodynamically unstable patients with CS or low cardiac output complicating AMI.

Single-center trials tend to provide larger treatment effects than multicenter trials: a systematic review.

OBJECTIVES: To assess whether the reported trial characteristics are associated with treatment effects on all-cause mortality within critical care medicine. STUDY DESIGN AND SETTING: We identified all eligible randomized controlled trials (RCTs) from Cochrane Reviews on patients with sepsis, septic shock, and cardiogenic shock. Risk of bias was judged on 12 trial characteristics, including the differentiation between single-center and multicenter trials. Hierarchical random-effects models quantified the impact of the risk of bias items on the reported effect estimates of mortality. RESULTS: Twelve meta-analyses that involved 82 RCTs were selected and judged. Single-center trials estimated a significant larger treatment effect compared with multicenter trials (ratio of odds ratios, 0.64; 95% confidence interval: 0.47, 0.87). Treatment effect tended to be overestimated with selective reporting of preplanned end points. Biases in different trial characteristics are unlikely to operate independently and may have modified these associations. CONCLUSION: The results of this study highlight a substantial difference in treatment effect estimates between single-center and multicenter trials. Therefore, we recommend that results from single-center trials should be cautiously used for decision making.

Influence of oral antiplatelet therapy on hemorrhagic complications of pacemaker implantation.

OBJECTIVE: We retrospectively assessed the incidence of hemorrhagic complications associated with pacemaker implantation in patients receiving one or more antiplatelet agents. DESIGN AND SETTING: Retrospective multicenter case-control study. Data were collected from three cardiac units in Germany from 2006 to 2010. METHODS: A total of 495 pacemaker patients were enrolled. 99 patients received dual antiplatelet therapy (aspirin and clopidogrel), 198 were given only aspirin and 198 had no antiplatelet therapy (control). Patients were matched for age and sex. Implant-related bleeding complications were defined as major bleeding, if surgical pocket exploration or blood transfusion were needed. Minor bleeding complications were defined as one or more of the following conditions: fall of hemoglobin content >1.5 g/dl not requiring blood transfusion; pocket hematoma; pocket effusion not requiring surgical revision. MEASUREMENTS AND RESULTS: Hemorrhagic complications were seen in 4/198 control patients and 6/198 aspirin-only patients [2 vs. 3 %, p = 0.5, OR = 1.52 (0.42-5.46)]. Patients undergoing dual antiplatelet therapy had significantly more bleeding complications than patients in the aspirin-only group [11/99: 11.1 vs. 3 %, p = 0.005, OR = 3.95 (1.43-11.16)]. Major complications occurred in 1/198 control patients and 2/198 aspirin-only patients [0.5 vs. 1 %, p = 0.6, OR = 2.01 (0.18-22.35)]. In contrast, 7/99 patients undergoing dual antiplatelet therapy exhibited major complications [7.1 vs. 1 %, p = 0.004, OR = 7.46 (1.52-36.50)]. CONCLUSIONS: Although in patients undergoing pacemaker implantation dual antiplatelet therapy with aspirin and clopidogrel caused a significant increase of bleeding complications, the use of aspirin alone was not associated with a significant increase in bleeding complications.

Evidence-based Management of Cardiogenic Shock After Acute Myocardial Infarction.

Guidelines for evidence-based management of patients with cardiogenic shock after acute myocardial infarction focuses on early revascularisation of the occluded coronary artery as well as on support of cardiac failure and improvement of impaired organ perfusion. Also of great importance is effective treatment of shock complications, especially acute respiratory failure and other forms of multiple organ dysfunction syndrome (MODS). Cardiovascular therapy has to be accompanied by best general intensive care of these critically ill patients with high mortality. Most lives can be saved by early revascularisation, and this class I recommendation has a high level of evidence. So far, most of the other guideline recommendations are of low evidence level, in most cases based on expert opinions. Recently, the Intra-aortic Balloon Pump in Cardiogenic Shock II (IABP SHOCK II) trial with 600 patients has shown that adjunctive IABP therapy - for long a class I recommendation - does not reduce 30-day and six-month motality.

A novel approach for transcoronary pacing in a porcine model.

BACKGROUND: Transcoronary pacing for the treatment of bradycardias during percutaneous coronary intervention (PCI) is a useful technique in interventional cardiology. The standard technique is unipolar pacing with the guidewire in the coronary artery against a cutaneous patch electrode. We developed a novel approach for transcoronary pacing by using intravascular electrodes in different positions in the aorta in a porcine model. METHODS AND RESULTS: Unipolar transcoronary pacing was applied in 8 pigs under general anesthesia using a standard floppy guidewire in a coronary artery as the cathode with additional insulation of the guidewire by a monorail angioplasty balloon. Intravascular electrodes positioned in the aorta thoracalis and the aorta abdominalis served as indifferent anodes. The efficacy of transcoronary pacing with intravascular anodal electrodes was assessed by measurement of threshold and impedance data and the magnitude of the epicardial electrogram in comparison to unipolar transvenous pacing using the same indifferent anodal electrodes. Transcoronary pacing with the guidewire-balloon combination using indifferent intravascular electrodes was effective in all cases. Transcoronary pacing thresholds obtained against the indifferent coil electrodes in the aorta thoracalis (0.8 ± 0.5 V) and in the aorta abdominalis (0.8 ± 0.5 V) were similar to those obtained with unipolar transvenous pacing (0.7 ± 0.3 V and 0.6 ± 0.2 V, respectively), whereas the tip-electrode in the aorta thoracalis serving as indifferent anode produced significantly higher pacing thresholds (guidewire, 2.8 ± 2.6 V; transvenous lead, 1.5 ± 0.8 V). The lower pacing threshold of the coil-electrodes was associated with significantly lower impedance values (aorta thoracalis, 285 ± 63 ohm; aorta abdominalis, 294 ± 61 ohm) as compared to the tip-electrode in the aorta thoracalis (718 ± 254 ohm). The amplitude of the epicardial electrogram acquired by the intracoronary guidewire was without significant differences between the indifferent electrodes. CONCLUSIONS: Transcoronary pacing in the animal model using a standard guidewire with balloon insulation and intravascular indifferent electrodes is depending on the optimal configuration of the anodal electrode. The use of intravascular coil electrodes with a sufficient surface area can produce 100% capture at thresholds comparable to transvenous pacing. Therefore, technical integration of these coil electrodes into the access sheath or the guiding catheter with respect to handling these tools in daily clinical practice in the catheterization laboratory could further facilitate the transcoronary pacing approach.