[Acute myocardial infarction in patients with ST-segment elevation myocardial infarction : ESC guidelines 2017]. / Akuter Myokardinfarkt bei Patienten mit ST-Strecken-Hebungs-Infarkt : ESC-Leitlinien 2017.

This article gives an update on the management of acute ST-segment elevation myocardial infarction (STEMI) according to the recently released European Society of Cardiology guidelines 2017 and the modifications are compared to the previous STEMI guidelines from 2012. Primary percutaneous coronary intervention (PCI) remains the preferred reperfusion strategy. New guideline recommendations relate to the access site with a clear preference for the radial artery, use of drug-eluting stents over bare metal stents, complete revascularization during the index hospitalization, and avoidance of routine thrombus aspiration. For periprocedural anticoagulation during PCI, bivalirudin has been downgraded. Oxygen treatment should be administered only if oxygen saturation is <90%. In cardiogenic shock, intra-aortic balloon pumps should no longer be used. New recommendations are in place with respect to the duration of dual antiplatelet therapy for patients without bleeding events during the first 12 months. Newly introduced sections cover myocardial infarction with no relevant stenosis of the coronary arteries (MINOCA), the introduction of new indicators for quality of care for myocardial infarction networks and new definitions for the time to reperfusion.

Interventional therapies in acute myocardial infarction complicated by cardiogenic shock.

Cardiogenic shock remains the most common cause of death in patients with acute myocardial infarction. Early revascularization of the infarct-related artery has been shown to reduce mortality and is the therapeutic cornerstone. The optimal revascularization strategy of additional non-culprit lesions remains yet to be determined. Further, uncertainties exist with respect to access site choice, antiplatelet regimen as well as mechanical support devices. This review outlines current evidence on the interventional management of cardiogenic shock complicating acute myocardial infarction.

[Thrombus aspiration in patients with acute myocardial infarction : Scientific evidence and guideline recommendations]. / Thrombusaspiration bei Patienten mit akutem Myokardinfarkt : Wissenschaftliche Evidenz und Empfehlungen in den Leitlinien.

Recent advances in percutaneous coronary intervention and antiplatelet therapy as well as faster door-to-balloon times have markedly improved the therapy of patients with acute myocardial infarction. However, impaired myocardial perfusion despite revascularization of the infarcted vessel remains an ongoing problem with high prognostic relevance. In initial clinical trials thrombus aspiration in addition to conventional percutaneous coronary intervention demonstrated benefits regarding coronary flow and myocardial perfusion and was therefore recommended in practice guidelines. These improvements in surrogate endpoints did not translate into a favorable clinical outcome in recent large-scale multicenter randomized trials investigating the routine use of thrombus aspiration in patients with acute myocardial infarction. Furthermore, an increased risk of stroke after thrombus aspiration raises safety concerns. Therefore, thrombus aspiration has been downgraded in the recent guideline updates. The current article reviews the evidence from clinical trials and the recommendations in practice guidelines regarding thrombus aspiration in acute myocardial infarction.

Left ventricular global function index assessed by cardiovascular magnetic resonance for the prediction of cardiovascular events in ST-elevation myocardial infarction.

BACKGROUND: The left ventricular performance index (LVGFI) as a comprehensive marker of cardiac performance integrates LV structure with global function within one index. In a prospective cohort study of healthy individuals the LVGFI demonstrated a superior prognostic value as compared to LV ejection fraction (LVEF). In patients after ST-segment elevation myocardial infarction (STEMI), however, the role of the LVGFI is unknown. Aim of this study was to investigate the relationship between the LVGFI and infarct characteristics as well as prognosis in a large multicenter STEMI population. METHODS: In total 795 STEMI patients reperfused by primary angioplasty (<12 h after symptom onset) underwent cardiovascular magnetic resonance (CMR) at 8 centers. CMR was completed within one week after infarction using a standardized protocol including LV dimensions, mass and function for calculation of the LVGFI. The primary clinical endpoint of the study was the occurrence of major adverse cardiac events (MACE). RESULTS: The median LVGFI was 31.2 % (interquartile range 25.7 to 36.6). Patients with LVGFI < median had significantly larger infarcts, less myocardial salvage, a larger extent of microvascular obstruction, higher incidence of intramyocardial hemorrhage and more pronounced LV dysfunction (p < 0.001 for all). MACE and mortality rates were significantly higher in the LVGFI < median group (p < 0.001 and p = 0.003, respectively). The LVGFI had an incremental prognostic value in addition to LVEF for prediction of all-cause mortality. CONCLUSIONS: The LVGFI strongly correlates with markers of severe myocardial and microvascular damage in patients with STEMI, offering prognostic information beyond traditional cardiac risk factors including the LVEF. TRIALS REGISTRATION: ClinicalTrials.gov: NCT00712101.

[Timing of invasive treatment in NSTEMI: as fast as in STEMI?]. / Zeitpunkt der invasiven Therapie beim NSTEMI: So schnell wie beim STEMI?

The optimal timing of invasive diagnosis and therapy in patients with non-ST-elevation myocardial infarction (NSTEMI) is still a matter of debate. The European Society of Cardiology recommends invasive diagnosis evaluation and revascularization for practically all patients with NSTEMI within 72 h. High risk and very high risk patients should be evaluated invasively with coronary angiography within 24 h or 2 h, respectively. The risk of the individual patient should be stratified by means of the Global Registry of Acute Coronary Events (GRACE) risk score. The recommendations and guidelines are based on the results of several randomized, controlled trials and are in accordance with other retrospective studies. However, observational studies indicate that in real life many high risk patients are not evaluated invasively by coronary angiography as timely as recommended.

Prognostic significance and relationship of worst lead residual ST segment elevation with myocardial damage assessed by cardiovascular MRI in myocardial infarction.

OBJECTIVE: To investigate the relation of residual worst lead ST segment elevation (WL-STE) after ST segment myocardial infarction (STEMI) with infarct size and microvascular injury assessed by cardiovascular magnetic resonance (CMR) imaging. BACKGROUND: WL-STE in patients with acute reperfused STEMI has been shown to identify high risk patients for major adverse cardiovascular events (MACE). However, the relation of WL-STE with myocardial damage is unknown. METHODS: In this multicentre study we analysed ECG data 90 min after primary percutaneous coronary intervention (PCI) in 763 STEMI patients. WL-STE was defined as the absolute magnitude of STE in the most affected lead on the post-PCI ECG. Patients were categorised into three groups (<1 mm, 1-2 mm, and ≥2 mm). CMR was performed within 1 week after infarction for comprehensive assessment of myocardial damage using a standardised protocol. The primary clinical endpoint was MACE defined as death, reinfarction, and new congestive heart failure within 12 months after infarction. RESULTS: WL-STE <1 mm, 1-2 mm, and ≥2 mm was present in 155 (20%), 328 (43%), and 280 (37%) patients, respectively. Myocardial damage determined by CMR demonstrated a graded relationship of infarct size (median (IQR) 13.3 (6.2-20.3)%LV vs 13.7 (7.6-21.3)%LV vs 22.5 (15.6-31.2)%LV, p<0.001), the myocardial salvage index (60.8 (37.0-84.5) vs 55.0 (36.6-73.9) vs 42.7 (26.2-58.2), p<0.001), and microvascular obstruction (0.0 (0.0-0.9)%LV vs 0.0 (0-1.0)%LV vs 1.2 (0.0-3.6)%LV, p<0.001) across the three groups. WL-STE ≥2 mm was strongly associated with MACE 12 month after infarction (HR 1.93, 95% CI 1.11 to 3.37; p=0.02). CONCLUSIONS: This largest CMR study to date correlating post-PCI WL-STE with markers of myocardial damage demonstrates that WL-STE is significantly associated with infarct size, myocardial salvage, microvascular obstruction, and MACE in a high risk STEMI population. TRIAL REGISTRATION NUMBER: NCT00712101.

Growth differentiation factor-15 in Takotsubo cardiomyopathy: diagnostic and prognostic value.

BACKGROUND: Growth differentiation factor-15 (GDF-15), a stress responsive cytokine, has emerged as a marker of adverse outcome in various cardiovascular diseases. Since GDF-15 has not been evaluated in patients with Takotsubo cardiomyopathy (TTC), the present study sought to investigate the diagnostic and prognostic value in this patient cohort. METHODS: A total of 22 patients presenting with TTC were matched for age and gender with 22 ST-segment elevation myocardial infarction (STEMI) patients. GDF-15 concentrations were measured at admission and 1 day thereafter. The primary clinical endpoint of the TTC cohort was the composite of death, cardiogenic shock, or new congestive heart failure within 6 months. RESULTS: TTC patients showed significantly higher GDF-15 values on admission compared to patients presenting with STEMI (median 3047 ng/l [interquartile range 2256-7572] versus median 1527 ng/l [interquartile range 1152-2677]; p=0.002). TTC patients with a biventricular ballooning pattern and patients experiencing major adverse cardiac events during the first 6 months after acute presentation showed significantly higher GDF-15 concentrations on admission (p=0.008 and p=0.005, respectively). Biventricular ballooning was identified as a predictor for elevated GDF-15 values on admission (p=0.03). High GDF-15 levels on admission were the only significant predictor for the combined clinical endpoint in multivariable regression analysis (p=0.02). CONCLUSION: TTC patients showed markedly high, but transient elevation of GDF-15 levels. Biventricular ballooning was associated with particularly high GDF-15 concentrations. Elevated GDF-15 values on admission were a strong predictor of adverse clinical outcome.

Reperfusion strategies in ST-segment elevation myocardial infarction.

ST-elevation myocardial infarction (STEMI) is a major cause of morbidity and mortality worldwide. Emergent reperfusion of the infarct related artery is the cornerstone of STEMI treatment in order to salvage myocardium and improve cardiovascular outcome. Basically, reperfusion strategies include fibrinolysis, primary percutaneous coronary intervention (PCI) or the combination of both methods. Clinical studies indicate that primary PCI is superior to fibrinolytic therapy when performed rapidly at experienced centers. However, physicians are often faced with the decision to either accept PCI-related delays due to transfer or to administer fibrinolysis immediately. A well structured regional system of STEMI care helps to select the appropriate reperfusion strategy and guarantee timely restoration of coronary blood flow. This article reviews the evidence behind the respective reperfusion therapies and summarizes current guidelines for STEMI management.

[Diagnosis and therapy of chronic myocardial ischemia. Role of cardiac magnetic resonance imaging]. / Diagnostik und Therapie der chronischen Myokardischämie. Rolle der kardialen Magnetresonanztomographie.

In patients with chronic coronary artery disease different therapeutic strategies, such as optimal medical therapy, revascularization by percutaneous coronary intervention or coronary artery bypass grafting have been shown to improve the prognosis and symptoms and yield proven superiority over other treatment strategies in different patient populations. Thus, individual assessment of cardiac function and structure is of paramount importance to choose the optimal therapeutic strategy and subsequently improve patient prognosis. In this setting cardiac magnetic resonance imaging (CMR) has been shown to provide important diagnostic information. Myocardial ischemia can be detected by either perfusion stress CMR demonstrating perfusion deficits indicative of hemodynamically relevant coronary artery stenosis or dobutamin stress CMR for objectifying wall motion abnormalities during stress. Both techniques are superior to single photon emission computerized tomography and stress echocardiography in specific patient populations. Myocardial viability can be assessed by means of end-diastolic wall thickness or delayed enhancement imaging which allows quantification of the transmural extent of scarring. Furthermore, low-dose dobutamin stress CMR can detect a contractile reserve. Delayed enhancement imaging leads to accurate results due to its high resolution, can be performed at rest requiring no stress within a short time period and is easy to analyze. Thus this technique can be recommended as the favored technique to assess myocardial viability. In the following article the CMR techniques for ischemia and viability testing will be presented and their role in diagnosis and therapy of chronic myocardial ischemia will be discussed.

Is percutaneous coronary intervention as effective as bypass surgery in left main stem coronary artery stenosis?

Recent advances in percutaneous coronary intervention (PCI) have rekindled interest in this treatment modality also in the setting of unprotected left main stenosis. Randomized trials reported a similar risk of death or myocardial infarction between PCI and coronary artery bypass grafting (CABG). However, rates of stroke were higher after CABG, whereas patients undergoing PCI had a higher risk of repeat revascularization. Although CABG remains the standard of care for left main stenosis in current guideline recommendations, PCI is considered a reasonable alternative in patients with low to intermediate anatomical complexity and at increased surgical risk. An interdisciplinary assessment is indispensable in order to choose the best treatment option for each individual patient.

Bypass surgery versus percutaneous coronary intervention for the treatment of unprotected left main disease. A meta-analysis of randomized controlled trials.

OBJECTIVE: We performed a meta-analysis of randomized controlled trials to compare coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for the treatment of de novo unprotected left main disease. BACKGROUND: Although CABG is accepted to be standard of care for revascularization of unprotected left main stenosis, PCI is increasingly being used as an alternative primary approach. METHODS: We searched for randomized, controlled trials comparing CABG and PCI for the treatment of unprotected left main disease. Major adverse cardiac and cerebrovascular events (all-cause death, myocardial infarction, stroke, and repeat revascularization) were analyzed. RESULTS: The search strategy identified 4 randomized controlled trials enrolling a total of 1,611 patients. Follow-up ranged between 1 and 2 years. There were no significant differences in the risk of death or myocardial infarction between the two treatment modalities. While the risk of stroke was significantly lower in patients undergoing PCI (risk ratio (RR) 0.26, 95% confidence interval (CI) 0.10-0.69, p = 0.007), the risk of repeat revascularization was higher among patients undergoing PCI (RR 1.94, 95% CI 1.43-2.61, p < 0.001). No relevant statistical heterogeneity across studies could be found. CONCLUSION: In this largest series of randomized patients with unprotected left main stenosis to date, the risk of death and myocardial infarction was comparable between CABG and PCI. However, patients undergoing CABG had a higher risk of stroke, whereas patients undergoing PCI were at a higher risk for repeat revascularization.

Effects of physical exercise versus rosiglitazone on endothelial function in coronary artery disease patients with prediabetes.

We conducted a three-arm, parallel-group, randomized, controlled trial to compare the effects of rosiglitazone and physical exercise on endothelial function in patients with coronary artery disease and impaired fasting glucose or impaired glucose tolerance over a 6-month period. Group A received rosiglitazone tablets 8 mg daily (n = 16), group B underwent a structured physical exercise programme (n = 15) and group C served as a control group (n = 12). At baseline and after 6 months, brachial artery ultrasound imaging was performed to assess reactive flow-mediated dilation (FMD). Rosiglitazone treatment and exercise both led to significant improvements in insulin resistance at 6 months, whereas no change was observed in control patients. FMD improved significantly in physical exercise patients, whereas no change could be observed in patients receiving rosiglitazone or in the control group. Between-group comparisons also showed a significant relative improvement in FMD in exercise patients compared with rosiglitazone.

Efavirenz plasma levels for the prediction of treatment failure in heavily pretreated HIV-1 infected patients.

OBJECTIVE: Efavirenz (EFV) plasma levels have been discussed as a predictor of treatment failure in HIV infected patients. The aim of this prospective, open-labeled, case-control study was to evaluate pretreated patients in regards to efavirenz plasma levels and efficacy of therapy. METHODS: Blood samples were obtained monthly from 33 patients receiving efavirenz in combination with other antiretroviral agents for at least 3 months. EFV plasma concentrations and potease inhibitor (PI) plasma levels were measured by high-performance liquid chromatography (HPLC). EFV plasma levels were correlated with efficacy. In patients with virologic failure genotypic resistance testing was performed. RESULTS: Mean efavirenz plasma levels (n = 240) of 33 patients were 3.119 +/- 2.497 ng/ml. There were no significant differences between median efavirenz plasma levels of 24 patients (72%) with a HIV-RNA < 20 copies/ml (2.168 ng/ml), 3 patients with HIV-RNA of 20 500 copies/ml (3.362 ng/ml), and 6 patients with a virologic failure (>500 copies/ml) (2.190 ng/ml) respectively. Efavirenz plasma levels below 1.000 ng/ml were found in 4/27 effective treated patients, and in 4/6 patients with virologic failure. In all patients with virologic failure multiple NRTI, NNRTI and PI mutations were found in genotypic resistance testing. CONCLUSION: An individual EFV plasma level below 1.000 ng/ml in one single measurement seems to be predictive of viral failure and the developement of genotypic resistance. Therapeutic drug monitoring of EFV might be helpful, especially in heavily pretreated patients, to reach long term sufficently effectiveness of therapy.

Triple antiviral re-therapy for chronic hepatitis C with interferon-alpha, ribavirin and amantadine in nonresponders to interferon-alpha and ribavirin.

BACKGROUND: Therapy options for patients with chronic hepatitis C who failed prior treatment are needed. In recent studies triple antiviral therapy with Interferon-alpha, ribavirin, and amantadine seemed to increase sustained virological response rates in this group. METHOD: To evaluate efficacy, side effects and safety of a triple re-therapy in an open labeled prospective study, we compared 23 nonresponders to interferon monotherapy (9 nonresponders, 3 relapsers, 11 with breakthrough) with 23 nonresponders to standard combination therapy (interferon plus ribavirin) (16 nonresponders, 7 breakthroughs). All outpatients enrolled for re-therapy received interferon-alpha 2a (6 mega units [MU] three times in week), ribavirin (1000-1200 mg daily in divided doses) and amantadine (200 mg daily) for six months. In case of virological re-therapy response (negative qualitative HCV RNA) study medication was continued with interferon monotherapy for another six months. RESULTS: Sustained virological response was achieved in 16 (35%) out of 46 prior therapy nonresponders. Response rates were dependent on pretreatment outcome. In the standard combination therapy group only 1 (6%) primary nonresponder achieved sustained response, but none of the 9 monotherapy nonresponders did. After primary breakthrough sustained response was seen in 8 of 11 (73%) patients in the interferon monotherapy and in 5 of 7 (71%) in the combination therapy group. Of 3 monotherapy relapsers 2 (66%) did also clear the virus sustained. Safety profile under triple therapy was similar to the previous therapy. Compliance was higher and side effects lower in those patients already experienced in combination therapy. CONCLUSION: In patients with a breakthrough or relapse after interferon monotherapy or standard combination therapy with interferon and ribavirin a re-therapy with a triple combination of interferon, ribavirin, and amantadine results in a high rate of sustained virological response.

Therapeutic drug monitoring of indinavir in HIV-infected patients undergoing HAART.

BACKGROUND: Therapeutic drug monitoring (TDM) of protease inhibitors (PI) is gaining increasing importance for the management of HIV-infected patients undergoing highly active antiretroviral therapy (HAART). The PI indinavir (IDV) is widely used in HAART regimens. Combinations of IDV with ritonavir (RTV) have been used to increase the plasma concentration of IDV. However, the desirable IDV concentration range in clinical practice remains to be elucidated. PATIENTS AND METHODS: To study the value of TDM for IDV in clinical practice, a retrospective analysis of 501 plasma samples of patients treated with IDV in various dosages was performed. IDV levels were determined during routine outpatient visits. Analysis was performed by high pressure liquid chromatography (HPlC) with UV detection. RESULTS: A widespread range of IDV plasma concentrations was seen both within and between patients. The mean IDV level during therapy with IDV 2.4 g/d was 3,260 ng/ml (95% CI: 2,903 ng/ml; 3,618 ng/ml). IDV levels at a dose of IDV 1.6 g/d in combination with RTV resulted in a mean IDV plasma concentration of 4,191 ng/ml (95% CI: 3,356 ng/ml; 5,026 ng/ml). There was no significant difference between plasma levels at the doses of 2.4 g/d and 1.6 g/d. 35 of all 130 patients treated with IDV reached only suboptimal IDV plasma concentrations below the limit of 150 ng/ml. There was no statistically significant difference between the number of patients below an IDV plasma concentration of 150 ng/ml in the various dosage regimens. CONCLUSION: During therapy with IDV in a b.i.d. scheme, similar IDV plasma concentrations and a comparable number of patients with subinhibitory plasma concentrations were observed when compared to a therapeutic regimen with t.i.d. dosing. In this study, even at various times of plasma sampling after oral ingestion, TCM facilitated the surveillance of patients compliance.

Efficacy and safety of an initial daily dosing regimen of interferon-alpha-2a in treatment-naive patients with chronic hepatitis C and HCV genotype 1.

Between January 1996 and February 1999 we treated two groups of patients with chronic hepatitis C and HCV genotype 1 according to different treatment regimens. 29 patients in group were treated in a prospective, open trial and received an initial dose of 6 MU Interferon-alpha-2a daily. In case of virologic response within the first 12 weeks of treatment a dosage reduction to 6 MU three times weekly was performed until the end of week 12 and 3 MU three times weekly thereafter until the completion of month 12. 35 patients in group 2 received 5 MU (Interferon-alpha-2b) or 6 MU (Interferon-alpha-2a) three times a week. If serum HCV RNA was negative after three months of treatment patients received 3 MU thrice weekly until completion of month 12. This regimen was considered standard therapy at the time of treatment. In both groups therapy was stopped in patients in whom HCV RNA remained detectable after 12 weeks of treatment or in patients who underwent virological breakthrough. The end point was a sustained virologic response defined as the absence of serum HCV RNA 6 months after treatment was completed. Primary response rates as defined by negative serum HCV RNA within the first 12 weeks of treatment were 59% in group 1 and 17% in group 2. Sustained response rates were 10% in group 1 and 3% in group 2. Initial daily dosing as in group 1 was therefore not associated with a higher sustained response rate compared to standard therapy. The safety profile was in accordance with the known side effects of interferon-alpha and was comparable in both treatment groups.