High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany.

BACKGROUND AND AIMS: Low-density lipoprotein cholesterol (LDL-C) is the main therapeutic target in the treatment of hypercholesterolemia. Small interfering RNA (siRNA) inclisiran is a new drug, which targets PCSK9 mRNA in the liver, reducing concentrations of circulating LDL-C. In randomized trials, inclisiran demonstrated a substantial reduction in LDL-C. The German Inclisiran Network (GIN) aims to evaluate LDL-C reductions in a real-world cohort of patients treated with inclisiran in Germany. METHODS: Patients who received inclisiran in 14 lipid clinics in Germany for elevated LDL-C levels between February 2021 and July 2022 were included in this analysis. We described baseline characteristics, individual LDL-C changes (%) and side effects in 153 patients 3 months (n = 153) and 9 months (n = 79) after inclisiran administration. RESULTS: Since all patients were referred to specialized lipid clinics, only one-third were on statin therapy due to statin intolerance. The median LDL-C reduction was 35.5% at 3 months and 26.5% at 9 months. In patients previously treated with PCSK9 antibody (PCSK9-mAb), LDL-C reductions were less effective than in PCSK9-mAb-naïve patients (23.6% vs. 41.1% at 3 months). Concomitant statin treatment was associated with more effective LDL-C lowering. There was a high interindividual variability in LDL-C changes from baseline. Altogether, inclisiran was well-tolerated, and side effects were rare (5.9%). CONCLUSION: In this real-world patient population referred to German lipid clinics for elevated LDL-C levels, inclisiran demonstrated a high interindividual variability in LDL-C reductions. Further research is warranted to elucidate reasons for the interindividual variability in drug efficacy.

[Antiplatelet or anticoagulative strategies after surgical/interventional valve treatment]. / Antithrombozytäre oder antikoagulative Strategie nach chirurgischer/interventioneller Klappenbehandlung.

At the end of August 2017 the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) published new joint guidelines for the treatment of valvular heart disease. These guidelines incorporate the scientific progress since the last version of the guidelines published in 2012. This article reviews current guideline recommendations for antiplatelet and anticoagulative therapy after surgical/interventional treatment of the aortic and mitral valves and discusses the underlying scientific evidence.

Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction.

Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15-25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO). We found 398 genes associated with lateMO and two genes with IS. Neither AAR, nor MSI showed significant correlations with gene expression. Genes correlating with lateMO were strongly related to several canonical pathways, including positive regulation of T-cell activation (p = 3.44 × 10-5), and regulation of inflammatory response (p = 1.86 × 10-3). Network analysis of multiple gene expression alterations associated with larger lateMO identified the following functional consequences: facilitated utilisation and decreased concentration of free fatty acid, repressed cell differentiation, enhanced phagocyte movement, increased cell death, vascular disease and compensatory vasculogenesis. In conclusion, the extent of lateMO after acute, reperfused STEMI correlated with altered activation of multiple genes related to fatty acid utilisation, lymphocyte differentiation, phagocyte mobilisation, cell survival, and vascular dysfunction.

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.

[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.

[MRI for myocarditis]. / MRT bei Myokarditis.

Cardiovascular magnetic resonance imaging (CMRI) has become the primary tool for the non-invasive assessment in patients with suspected myocarditis, especially after exclusion of acute coronary syndrome (ACS) for the differential diagnosis. Various MRI parameters are available which have different accuracies. Volumetric and functional ventricular assessment and the occurrence of pericardial effusion alone demonstrate only a poor sensitivity and specificity. The calculation of the T2-ratio (edema assessment), the early or global relative myocardial enhancement (gRE) and the late gadolinium enhancement (LGE), which represents irreversibly injured myocardium, are more specific parameters. All MRI parameters demonstrate the best accuracy in infarct-like acute myocarditis, whereas in chronic myocarditis sensitivity and specificity are less accurate. Therefore, a multisequential (at least two out of three parameters are positive) approach is recommended. The assessment of the value of newer, more quantitative MRI sequences, such as T1 and T2-mapping is still under investigation.

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.