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Aims: To evaluate whether CMR-derived RV assessment can facilitate risk stratification among patients undergoing transcatheter mitral valve repair (TMVR). Background: In patients undergoing TMVR, only limited data exist regarding the role of RV function. Previous studies assessed the impact of pre-procedural RV dysfunction stating that RV failure may be associated with increased cardiovascular mortality after the procedure. Methods: Sixty-one patients underwent CMR, echocardiography and right heart catheterization prior TMVR. All-cause mortality and heart failure hospitalizations were assessed during 2-year follow-up. Results: According to RV ejection fraction (RVEF) <46%, 23 patients (38%) had pre-existing RV dysfunction. By measures of RV end-diastolic volume index (RVEDVi), 16 patients (26%) revealed RV dilatation. Nine patients (15%) revealed both. RV dysfunction was associated with increased right and left ventricular volumes as well as reduced left ventricular (LV) ejection fraction (all p<0.05). During follow-up, 15 patients (25%) died and additional 14 patients (23%) were admitted to hospital due to heart failure symptoms. RV dysfunction predicted all-cause mortality even after adjustment for LV function. Similarly, RVEDVi was a predictor of all-cause mortality even after adjustment for LVEDVi. Kaplan-Meier survival analysis unraveled that, among patients presenting with CMR indicative of both, RV dysfunction and dilatation, the majority (78%) experienced an adverse event during follow-up (p<0.001). Conclusion: In patients undergoing TMVR, pre-existing RV dysfunction and RV dilatation are associated with reduced survival, in progressive additive fashion. The assessment of RV volumes and function by CMR may aid in risk stratification prior TMVR in these high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. Objectives: To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). Patients: Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors. Results: At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively. Conclusions: Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Objectives: This study was designed to identify the multivariate effect of clinical risk factors on high on-treatment platelet reactivity (HPR) and 12 months major adverse events (MACE) under treatment with aspirin and clopidogrel in patients undergoing non-urgent percutaneous coronary intervention (PCI). Methods: 739 consecutive patients with stable coronary artery disease (CAD) undergoing PCI were recruited. On-treatment platelet aggregation was tested by light transmittance aggregometry. Clinical risk factors and MACE during one-year follow-up were recorded. An independent population of 591 patients served as validation cohort. Results: Degree of on-treatment platelet aggregation was influenced by different clinical risk factors. In multivariate regression analysis older age, diabetes mellitus, elevated BMI, renal function and left ventricular ejection fraction were independent predictors of HPR. After weighing these variables according to their estimates in multivariate regression model, we developed a score to predict HPR in stable CAD patients undergoing elective PCI (PREDICT-STABLE Score, ranging 0-9). Patients with a high score were significantly more likely to develop MACE within one year of follow-up, 3.4% (score 0-3), 6.3% (score 4-6) and 10.3% (score 7-9); odds ratio 3.23, P=0.02 for score 7-9 vs. 0-3. This association was confirmed in the validation cohort. Conclusions: Variability of on-treatment platelet function and associated outcome is mainly influenced by clinical risk variables. Identification of high risk patients (e.g. with high PREDICT-STABLE score) might help to identify risk groups that benefit from more intensified antiplatelet regimen. Additional clinical risk factor assessment rather than isolated platelet function-guided approaches should be investigated in future to evaluate personalized antiplatelet therapy in stable CAD-patients. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation promotes atherosclerosis in cardiovascular disease and is a major prognostic factor for patients undergoing percutaneous coronary intervention (PCI). Macrophage migration inhibitory factor (MIF) is involved in the progress of atherosclerosis and plaque destabilization and plays a pivotal role in the development of acute coronary syndromes (ACS). Little is known to date about the clinical impact of MIF in patients with symptomatic coronary artery disease (CAD). Methods and Results: In a pilot study, 286 patients with symptomatic CAD (n = 119 ACS, n = 167 stable CAD) undergoing PCI were consecutively evaluated. 25 healthy volunteers served as control. Expression of MIF was consecutively measured in patients at the time of PCI. Baseline levels of interleukin 6 (IL-6), "regulated upon activation, normal T-cell expressed, and secreted" (RANTES) and monocyte chemoattractant protein-1 (MCP-1) were measured by Bio-Plex Cytokine assay. C-reactive protein (CRP) was determined by Immunoassay. Patients with ACS showed higher plasma levels of MIF compared to patients with stable CAD and control subjects (median 2.85 ng/mL, interquartile range (IQR) 3.52 versus median 1.22 ng/mL, IQR 2.99, versus median 0.1, IQR 0.09, p<0.001). Increased MIF levels were associated with CRP and IL-6 levels and correlated with troponin I (TnI) release (spearman rank coefficient: 0.31, p<0.001). Patients with ACS due to plaque rupture showed significantly higher plasma levels of MIF than patients with flow limiting stenotic lesions (p = 0.002). Conclusion: To our knowledge this is the first study, demonstrating enhanced expression of MIF in ACS. It is associated with established inflammatory markers, correlates with the extent of cardiac necrosis marker release after PCI and is significantly increased in ACS patients with "culprit" lesions. Further attempts should be undertaken to characterize the role of MIF for risk assessment in the setting of ACS. [ABSTRACT FROM AUTHOR]

Objective : Monocyte infiltration is a critical step in the pathophysiology of plaque instability in coronary artery disease (CAD). Macrophage migration inhibitory factor (MIF) is involved in atherosclerotic plaque progression and instability leading to intracoronary thrombosis. Gremlin-1 (Grem1) has been recently identified as endogenous inhibitor of MIF. To date there are no data on the clinical impact of this interaction in cardiovascular patients. Methods and results : Plasma levels of MIF and Grem1 were determined by enzyme-linked immunoassay in patients with acute coronary syndromes (ACS, n = 120; stable CAD, n = 166 and healthy control subjects, n = 25). MIF levels were significantly increased in ACS compared to stable CAD and healthy control (ACS: median 2.85; IQR 3.52 ng/ml; versus SAP: median 1.22; IQR 2.99 ng/ml; versus healthy control: median 0.10; IQR 0.09 ng/ml, p < 0.001). Grem1 levels were significantly higher in ACS and stable CAD patients compared to healthy control (ACS: median 211.00; IQR 130.47 ng/ml; SAP: median 220.20; IQR 120.93 ng/ml, versus healthy control: median 90.57; IQR 97.68 ng/ml, p < 0.001). Grem1/MIF ratio was independently associated with ACS, whereas the single parameters were not associated with the presence of ACS. Furthermore, Grem1/MIF ratio was associated with angiographic signs of intracoronary thrombi and severity of thrombus burden. Conclusion : These novel findings suggest a potential role of Grem1/MIF ratio to indicate acuity of CAD and the grade of plaque stability. Prospective angiographic cohort studies involving plaque imaging techniques are warranted to further characterize the prognostic role of this novel risk marker in CAD patients. [ABSTRACT FROM AUTHOR]

Risk prediction with the Global Registry of Acute Coronary Events (GRACE) risk model is guideline-recommended in acute coronary syndrome (ACS) patients. However, the performance of more contemporary scores derived from ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and National Cardiovascular Data (NCDR) registries remains incompletely understood. We aimed to compare these models in German ACS patients. A total of 1567 patients with (Non-)ST-segment elevation myocardial infarction (NSTEMI: 1002 patients, STEMI: 565 patients) undergoing invasive management at University Hospital Düsseldorf (Germany) from 2014 to 2018 were included. Overall in-hospital mortality was 7.5% (NSTEMI 3.7%, STEMI 14.5%). Parameters for calculation of GRACE 1.0, GRACE 2.0, ACTION and NCDR risk models and in-hospital mortality were assessed and risk model performance was compared. The GRACE 1.0 risk model for prediction of in-hospital mortality discriminated risk superior (c-index 0.84) to its successor GRACE 2.0 (c-index 0.79, p GRACE1.0vsGRACE2.0 = 0.0008). The NCDR model performed best in discrimination of risk in ACS overall (c-index 0.89; p ACTIONvsNCDR < 0.0001; p GRACEvsNCDR < 0.0001) and showed superior performance compared to GRACE in NSTEMI and STEMI subgroups (p GRACEvsNCDR both < 0.02). ACTION and GRACE risk models performed comparable to each other (both c-index 0.84, p GRACEvsACTION = 0.68), with advantages for ACTION in NSTEMI patients (c-index 0.87 vs. 0.84 (GRACE); p GRACEvsACTION = 0.02). ACTION and GRACE 2.0 showed the most accurate calibration of all models. In a contemporary German patient population with ACS, modern NCDR and ACTION risk models showed superior performance in prediction of in-hospital mortality compared to the gold-standard GRACE model. • External validation study of updated NCDR, GRACE and ACTION risk models for mortality risk prediction in German ACS patients. • NCDR and -to a lesser extent- ACTION risk models discriminated risk for in-hospital mortality better than GRACE models. • ACTION and GRACE 2.0 showed the most accurate calibration of all risk models. [ABSTRACT FROM AUTHOR]

Background . Functional recovery and prognosis after acute coronary syndromes (ACS) are mainly driven by the extent of reperfusion injury and myocardial repair mechanisms. Transforming growth factor-beta 1 (TGF-β1) is critically involved in cardiac injury, repair and remodeling. In this study, we investigated the prognostic role of platelet TGF-β1 surface expression and circulating TGF-β1 levels in patients with coronary artery disease (CAD). Methods and results . Expression of TGF-β1 in platelets and circulating TGF-β1 levels were investigated by flow cytometry and ELISA, respectively, among patients with ACS and stable CAD undergoing percutaneous coronary intervention (PCI). In a cohort study, platelet and circulating TGF-β1 was measured in 299 patients with symptomatic CAD (stable CAD = 145, ACS = 154) at the time of PCI. The primary combined endpoint was defined as death and/or STEMI during 12-month follow-up. Platelets expressed TGF-β1 and circulating TGF-β1 showed a weak, but significant negative correlation. TGF-β1 surface expression was significantly elevated on platelets in ACS patients compared to patients with stable CAD (median MFI 13.4 vs. median MFI 11.7, p = 0.003). During follow-up, lower platelet expression of TGF-β1 was associated with all-cause mortality (median MFI 11.0 vs. median MFI 13.9, p = 0.011) as well as for the combined endpoint of death and/or STEMI, (median MFI 10.8 vs. median MFI 13.9, p = 0.006). In multivariate analysis platelet TGF-β1 expression was independently associated with the combined primary endpoint in the overall cohort (Hazard Ratio 0.31, 95% Confidence Interval 0.11–0.89, p = 0.029) and was strongly associated with prognosis in ACS patients. There was no significant association of circulating TGF-β1 levels neither with the presence of ACS nor the occurrence of the primary endpoint. Conclusion . These findings highlight a potential role of platelet expressed TGF-β1 in ACS and indicate a prognostic value of TGF-β1 on clinical outcomes in patients with acute coronary syndromes. Large scale studies are warranted to further evaluate the regulatory mechanisms of platelet TGF-β1 expression- and its prognostic impact in CAD. [ABSTRACT FROM AUTHOR]

Objectives: Bempedoic acid (BA) is a novel oral low-density lipoprotein cholesterol lowering drug. This systematic review and meta-analysis aims to assess efficacy and safety for clinical outcomes in high cardiovascular (CV) risk patients., Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Embase, ClinicalTrials.gov, Clinical Trial Results and the American College of Cardiology web site were searched., Study Selection: Randomised controlled trials (RCTs) of BA versus placebo in high CV risk patients reporting clinical outcomes were included., Main Outcomes and Measures: Primary efficacy outcomes were major adverse cardiovascular events (MACE), all-cause mortality, CV mortality and non-fatal myocardial infarction (MI). Safety outcomes included new onset or worsening of diabetes mellitus (DM), muscular disorders, gout and worsening of renal function., Results: Six RCTs with a total of 3956 patients and follow-ups of four to 52 weeks were identified. Heterogeneity mainly derived from differing follow-up duration and baseline CV risk. No difference in MACE (OR 0.84; 95% CI 0.61 to 1.15), all-cause mortality (OR 2.37; CI 0.80 to 6.99) and CV mortality (OR 1.66; CI 0.45 to 6.04) for BA versus placebo was observed. BA showed beneficial trends for non-fatal MI (OR 0.57; CI 0.32 to 1.00) and was associated with a lower risk of new-onset or worsening of DM (OR 0.68; CI 0.49 to 0.94), but higher risk of gout (OR 3.29; CI 1.28 to 8.46) and a trend for muscular disorders (OR 2.60; CI 1.15 to 5.91) and worsening of renal function (OR 4.24; CI 0.98 to 18.39)., Conclusion: BA in high CV risk patients showed no significant effects on major CV outcomes in short-term follow-up. Unfavourable effects on muscular disorders, renal function and gout sound a note of caution. Hence, further studies with longer term follow-up in carefully selected populations are needed to clarify the risk/benefit ratio of this novel therapy., Competing Interests: Competing interests: MB reported personal fees for speaking at an expert meeting in lipidology sponsored by Daiichi-Sankyo after primary submission of the current work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The treatment of pregnant patients with a cardiovascular disease is a special challenge to deal with. Before getting pregnant all cardiac patients should get medical advice accordingly to their risk profile in the modified World Health Organization classification of maternal cardiovascular risk. This article has the aim to give an overview of the new or changed recommendations of the new ESC-Guideline for the management of cardiovascular diseases during pregnancy., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Aims: Percutaneous coronary intervention (PCI)-related risks are increased among patients with left main disease (LMD). The aim was to evaluate the impact of antithrombotic therapy on outcomes after LMD PCI in a predominantly ACS population., Methods and Results: One hundred and seventy-seven patients undergoing LMD PCI were identified in a pooled dataset of 14,326 patients from three large randomised trials comparing treatment with heparin plus glycoprotein IIb/IIIa inhibitors (GPI) or bivalirudin alone, including the REPLACE-2, ACUITY and HORIZONS-AMI trials. Overall, net adverse clinical events (NACE) and non-CABG major bleedings at 30 days occurred more frequently in patients undergoing LMD PCI compared to the overall non-LMD PCI population (NACE: 19.8% vs. 10.6%, p≤0.001, major bleeding: 9.6% vs. 4.6%, p≤0.001). In the LMD group, bivalirudin was associated with significantly less non-CABG related major bleeding compared to heparin+GPI (4.5% versus 14.6%, relative risk [RR] 0.27, 95% CI: 0.09-0.83; p=0.013), while the composite ischaemic endpoint (death/MI/TVR) at 30 days was similar in the two groups (11.4% vs. 12.4%, p=0.513) resulting in a benefit on NACE for bivalirudin over heparin+GPI (14.8% vs. 24.7%; RR 0.53; p=0.039)., Conclusions: Among patients undergoing LMD PCI, the use of bivalirudin instead of heparin+GPI resulted in significantly less major bleeding and improved short-term net clinical outcome. Bivalirudin may be the preferred anticoagulation strategy in LMD PCI patients.