Implications of ACC/AHA Versus ESC/EAS LDL-C Recommendations for Residual Risk Reduction in ASCVD: A Simulation Study From DA VINCI.

PURPOSE: Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (< 70 vs. < 55 mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated. METHODS: DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy (LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C ≥ 70 mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of < 70 or < 55 mg/dl (LDL-C of 69 or 54 mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs and ARRs) were simulated. RESULTS: Of the 2039 patients, 61% did not achieve LDL-C < 70 mg/dl. For patients with LDL-C ≥ 70 mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54 mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively. CONCLUSION: In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10 years versus the ACC/AHA approach.

Lipid lowering therapy in primary and secondary prevention in Austria: are LDL-C goals achieved? : Results from the DA VINCI study.

BACKGROUND: Cardiovascular disease (CVD) is the most frequent cause of death in Austria. The European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend intensive lipid lowering therapy (LLT) in patients at high or very high CV risk. Lipid management and achievement of low-density lipoprotein cholesterol (LDL-C) goals in Austria have not recently been assessed. METHODS: Subgroup analysis for Austria of a European 18 country, cross-sectional, observational study. Patients received LLT for primary (PP) or secondary prevention (SP). Data including LLT in the preceding 12 months and most recent LDL­C were collected during a single visit between June 2017 and November 2018. Achievement of the risk-based 2016 and 2019 ESC/EAS LDL­C goal while receiving stabilized LLT was assessed. RESULTS: A total of 293 patients were enrolled from 8 Austrian sites, of which 200 (PP = 104, SP = 96) received stabilized LLT at the LDL­C measurement date. Overall, 58% (71% PP, 43% SP) and 38% (52% PP, 23% SP) achieved the risk-based 2016 and 2019 goals, respectively. Most patients received moderate-intensity statin monotherapy (46%), while 34% used high-intensity statin monotherapy. Combination therapy of moderate/high-intensity statin with ezetimibe (12%), or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors with statin ± ezetimibe (1%), was used infrequently. CONCLUSION: The current Austrian routine lipid management using mainly moderate-intensity or high-intensity statin monotherapy is insufficient to attain ESC/EAS guideline goals, in particular the more stringent 2019 recommendations, a situation comparable to other participating European countries. In addition to switching to and optimizing doses of high-intensity statins, a combination with ezetimibe or PCSK9 inhibitors will be needed in many cases.

Improved in-hospital outcome for radial access in a large contemporary cohort of primary percutaneous coronary intervention.

BACKGROUND: Randomised controlled trials have shown diverse results for radial access in patients undergoing primary percutaneous coronary intervention (PPCI). Moreover, it is questionable whether radial access improves outcome in patients with cardiogenic shock undergoing PPCI. We aimed to investigate the outcome according to access site in patients with or without cardiogenic shock, in daily clinical practice. METHODS: For the present analysis we included 9,980 patients undergoing PPCI between 2012 and 2018, registered in the multi-centre, nationwide registry on PCI for myocardial infarction (MI). In-hospital mortality, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE) until discharge were compared between 4,498 patients with radial (45%) and 5,482 patients with femoral (55%) access. RESULTS: Radial compared to femoral access was associated with lower in-hospital mortality (3.5% vs. 7.7%; P<0.01). Multivariable logistic regression analysis confirmed reduced in-hospital mortality [odds ratio (OR) 0.57, 95% confidence interval (CI): 0.43 to 0.75]. Furthermore, MACE (OR 0.60, 95% CI: 0.47 to 0.78) as well as NACE (OR 0.59, 95% CI: 0.46 to 0.75) occurred less frequently in patients with radial access. Interaction analysis with cardiogenic shock showed an effect modification, resulting in lower mortality in PCI via radial access in patients without, but no difference in those with cardiogenic shock (OR 1.78, 95% CI: 1.07 to 2.96). CONCLUSIONS: Radial access for patients with acute MI undergoing PPCI is associated with improved survival in a large contemporary cohort of daily practice. However, this beneficial effect is restricted to hemodynamically stable patients.

EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study.

AIMS: To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement. METHODS AND RESULTS: An 18 country, cross-sectional, observational study of patients prescribed LLT for primary or secondary prevention in primary or secondary care across Europe. Between June 2017 and November 2018, data were collected at a single visit, including LLT in the preceding 12 months and most recent LDL-C. Primary outcome was the achievement of risk-based 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) LDL-C goal while receiving stabilized LLT; 2019 goal achievement was also assessed. Overall, 5888 patients (3000 primary and 2888 secondary prevention patients) were enrolled; 54% [95% confidence interval (CI) 52-56] achieved their risk-based 2016 goal and 33% (95% CI 32-35) achieved their risk-based 2019 goal. High-intensity statin monotherapy was used in 20% and 38% of very high-risk primary and secondary prevention patients, respectively. Corresponding 2016 goal attainment was 22% and 45% (17% and 22% for 2019 goals) for very high-risk primary and secondary prevention patients, respectively. Use of moderate-high-intensity statins in combination with ezetimibe (9%), or any LLT with PCSK9 inhibitors (1%), was low; corresponding 2016 and 2019 goal attainment was 53% and 20% (ezetimibe combination), and 67% and 58% (PCSK9i combination). CONCLUSION: Gaps between clinical guidelines and clinical practice for lipid management across Europe persist, which will be exacerbated by the 2019 guidelines. Even with optimized statins, greater utilization of non-statin LLT is likely needed to reduce these gaps for patients at highest risk.

Evaluation of the Manchester triage system for patients with acute coronary syndrome.

BACKGROUND: An early diagnosis of acute coronary syndrome (ACS) is crucial for treatment and prognosis. The aim of this study was to evaluate the Manchester triage system (MTS) for patients with ACS, e.g. ST-segment elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (N-STEMI) and unstable angina pectoris (UAP). METHODS: Retrospective analysis of patients diagnosed with ACS (STEMI, N­STEMI and UAP) who were triaged in the emergency department (ED) with the MTS. RESULTS: In this study 282 patients with ACS (STEMI: 34.0%, N­STEMI: 61.7%, UAP: 4.3%) were triaged as MTS level 1 (immediate assessment): 0.4%, MTS level 2 (very urgent): 51.4%, MTS level 3 (urgent): 41.5%, MTS level 4 (standard): 6.7%, MTS level 5 (non-urgent): 0%. We observed significantly lower mean MTS levels in males (male: 2.48 ± 0.59, female: 2.68 ± 0.68, p = 0.02) and in patients younger than 80 years (age <80 years: 2.50 ± 0.61, age ≥80 years: 2.70 ± 0.67, p = 0.03). We did not find a significant difference of mean MTS levels in different types of ACS (STEMI: 2.46 ± 0.6, N­STEMI: 2.59 ± 0.64, STEMI vs N­STEMI: p = 0.11, UAP: 2.67 ± 0.65, STEMI vs UAP: p = 0.26) and with respect to diabetes (diabetic: 2.47 ± 0.57, non-diabetic: 2.58 ± 0.65, p = 0.13). The in-hospital mortality was 2.5% (MTS level 2: n = 3, MTS level 3: n = 3, MTS level 4: n = 1). CONCLUSION: The majority of patients with ACS were classified as MTS levels 2 and 3. There was no significant difference of mean MTS levels in patients with STEMI, NSTEMI and UAP. In order to assure an early diagnosis of STEMI, an electrocardiogram (ECG) should be carried out immediately or at least within 10 min after first medical contact in the ED in all patients suspected for ACS, irrespective of the assigned MTS level.

[Austrian Consensus on High Blood Pressure 2019]. / Österreichischer Blutdruckkonsens 2019.

Elevated blood pressure remains a major cause of cardiovascular disease, disability, and premature death in Austria, with suboptimal rates of detection, treatment and control also in recent years. Management of hypertension is a common challenge for physicians with different spezializations. In an attempt to standardize diagnostic and therapeutic strategies and, ultimately, to increase the rate of patients with controlled blood pressure and to decrease the burden of cardiovascular disease, 13 Austrian medical societies reviewed the evidence regarding prevention, detection, workup, treatment and consequences of high blood pressure in general and in various clinical scenarios. The result is presented as the first national consensus on blood pressure. The authors and societies involved are convinced that a joint national effort is needed to decrease hypertension-related morbidity and mortality in our country.

Radial versus femoral access site for percutaneous coronary intervention in patients suffering acute myocardial infarction : A randomized prospective multicenter trial.

BACKGROUND: Transradial access (TRA) in percutaneous coronary intervention (PCI) is a widely used standard technique with lower complication rates compared to transfemoral access (TFA). The aim of this study was to evaluate the impact of TRA versus TFA for PCI on clinically significant vascular access complications in the setting of acute myocardial infarction (AMI). METHODS: This multicenter study randomly assigned 250 patients in a 1:1 fashion (TRA vs. TFA) admitted with or without ST-segment elevation AMI undergoing immediate PCI. The primary endpoint was defined as the occurrence of hematoma, pseudo-aneurysm or local bleeding at the access site requiring any further intervention and/or prolonged hospital stay. Radiation exposure to the patient and operator was also investigated. RESULTS: In the study cohort (N = 250 patients, mean age 62 ± 12.7 years, 76% males) 5 patients (2%) achieved the primary endpoint without a significant difference between groups, 4 out of 125 (3.2%) in the TFA group and 1 out of 125 (0.8%) in the TRA group (p = 0.17). Access site hematoma was significantly more frequent in the TFA group compared to the TRA group (24.8% vs. 8.8%, respectively; p < 0.0007). Local bleeding was only seen in the TFA group (3.2% vs. 0%, p = 0.04). Time intervals from admission to catheter laboratory to first balloon inflation were longer in the TRA compared to the TFA group (34 ± 17 min vs 29.5 ± 13 min, respectively; p = 0.018). Radiation exposure to the patient and operator was identical. CONCLUSION: The use of TRA was accompanied by lower rates of access site complications; however, the need for subsequent treatment or prolonged hospital stays was not observed using either of the two access approaches.

[LDL-cholesterol and cardiovascular events: the lower the better?] / LDL-Cholesterin und kardiovaskuläre Ereignisse: je niedriger desto besser?

For over 30 years, intensive research efforts investigated the role of LDL cholesterol in the pathogenesis of cardiovascular disease. In various settings, large statin trials showed an association between LDL cholesterol levels and cardiovascular event rates. This association is often referred to as the 'LDL cholesterol hypothesis'. More recent trials on agents with totally different modes of action confirmed this association and indicated a causal relationship between lower LDL cholesterol levels and improved cardiovascular outcomes. It has been proposed to term this causal relationship the 'LDL cholesterol principle'. It is to be expected that currently ongoing outcomes trials will further support the assumption of a causal relationship and will finally offer an armamentarium to therapists that will enable individualized treatment of dyslipidemias and their sequelae.

In-Hospital Outcome Comparing Bivalirudin to Heparin in Real-World Primary Percutaneous Coronary Intervention.

Randomized controlled trials have shown conflicting results regarding the outcome of bivalirudin in primary percutaneous coronary intervention (PPCI). The aim of this study was to evaluate the in-hospital outcomes of patients receiving heparin or bivalirudin in a real-world setting of PPCI: 7,023 consecutive patients enrolled in the Austrian Acute PCI Registry were included between January 2010 and December 2014. Patients were classified according to the peri-interventional anticoagulation regimen receiving heparin (n = 6430) or bivalirudin (n = 593) with or without GpIIb/IIIa inhibitors (GPIs). In-hospital mortality (odds ratio [OR] 1.13, 95% confidence interval [CI] 0.57 to 2.25, p = 0.72), major adverse cardiovascular events (OR 1.18, 95% CI 0.65 to 2.14, p = 0.59), net adverse clinical events (OR 1.01, 95% CI 0.57 to 1.77, p = 0.99), and TIMI non-coronary artery bypass graft-related major bleeding (OR 0.41, 95% CI 0.09 to 1.86, p = 0.25) were not significantly different between the groups. However, we detected potential effect modifications of anticoagulants on mortality by GPIs (OR 0.12, 95% CI 0.01 to 1.07, p = 0.06) and access site (OR 0.25, 95% CI 0.06 to 1.03, p = 0.06) favoring bivalirudin in femoral access. In conclusion, this large real-world cohort of PPCI, heparin-based anticoagulation showed similar results of short-term mortality compared with bivalirudin. We observed a potential effect modification by additional GPI use and access favoring bivalirudin over heparin in femoral, but not radial, access.

Electrocardiogram changes and wall motion abnormalities in the acute phase of Tako-Tsubo syndrome.

BACKGROUND: The Tako-Tsubo syndrome is still rarely diagnosed in patients presenting with symptoms of acute myocardial ischaemia. It is accompanied by wall motion abnormalities of the left ventricle but significant narrowings or occlusions of epicardial coronary arteries are absent. We investigated a potential relationship between electrocardiogram (ECG) changes, wall motion abnormalities and gender influence of Tako-Tsubo syndrome in an Austrian cohort of Tako-Tsubo syndrome patients. METHODS AND RESULTS: We were recently able to describe four different anatomical types of Tako-Tsubo syndrome in 153 patients of the Austrian Tako-Tsubo syndrome registry. In the present retrospective analysis we investigated ischaemia-related changes in the first diagnostic ECG for the different types of Tako-Tsubo syndrome: the apical and the combined apical-midventricular type showed most frequently a ST elevation (41.1% and 35.3%), whereas the midventricular type of Tako-Tsubo syndrome was more often accompanied by T wave inversion (60%). ECG changes in relation to the Tako-Tsubo syndrome type were similar in women and men. There was no difference in the prevalence of clinical complications among patients presenting with ST elevation or left bundle branch block (14.5%) compared with patients without ST elevation (10.4%) (p=0.476). CONCLUSION: Patients with Tako-Tsubo syndrome show characteristic ECG changes in the first diagnostic ECG which are associated to some extent with the anatomical type of Tako-Tsubo syndrome, but these ECG changes were not related to clinical outcome.

Familial Himalayan p wave and left ventricular hypertrabeculation/noncompaction.

BACKGROUND: "Himalayan P waves," are reported in congenital heart disease and cardiomyopathies. METHODS: We report a family with hypertrophic cardiomyopathy, Himalayan P waves, extensive focal right atrial wall thickening and left ventricular hypertrabeculation/noncompaction (LVHT). RESULTS: The father received a pacemaker and underwent heart transplantation because of hypertrophic cardiomyopathy. His daughters showed Himalayan P waves and right atrial wall thickening. LVHT was diagnosed in sister A at age 23 years and developed in sister B between 42 and 46 years. In sister A the heart rate continuously declined. She refused implantation of a pacemaker and died with 49 years. Sister B, suffers from bradycardia. CONCLUSIONS: Himalayan P waves are due to focal right atrial wall thickening, may be familially and associated with LVHT.

Stress-induced cardiomyopathy (Tako-Tsubo syndrome) in Austria.

BACKGROUND: Tako-Tsubo syndrome (TS) is a still rarely diagnosed clinical syndrome, which is characterized by acute onset of chest pain, transient cardiac dysfunction with (frequently) reversible wall motion abnormalities (WMAs), but with no relevant obstructive coronary artery disease. METHODS AND RESULTS: Among 179 consecutive patients with proven diagnosis of TS that were retrospectively analysed in this multicentre registry, women represented the majority of patients (94%) while only 11 men (6%) developed TS. Mean age was 69.1±11.5 years (range 35-88 years). Cardinal symptoms of TS, which led to admission, were acute chest pain (82%) and dyspnoea (32%), respectively. All patients demonstrated typical WMAs, whereby four different types of WMAs could be defined: (1) a more common apical type of TS (n=89; 50%); (2) a combined apical and midventricular form of TS (n=23; 13%); (3) the midventricular TS (n=6; 3%); and (4) an unusual type of basal WMAs of the left ventricle (n=3). Only in 101 patients (57%), a clear causative trigger for onset of symptoms could be identified. In-hospital cardiovascular complications occurred in 25 patients (14%) and consisted of cardiac arrhythmias in 10 patients (40%), cardiogenic shock in six patients (24%), cardiac decompensation in eight patients (32%) and cardiovascular death in one patient, respectively. Echocardiographic control of left ventricular function after the initial measurement was available in almost 70% of the patients: complete recovery of WMAs was found in 73 patients (58.87%); 49 patients (39.52%) showed persistent WMAs. Recurrences of TS were only seen in four patients. During the follow-up period, 13 patients died: three of cardiovascular causes and 10 of non-cardiac causes. In-hospital mortality was 0.6%, 30-day mortality was 1.3% and 2-year mortality was 6.7%. CONCLUSIONS: This study represents to date the largest series of patients suffering from TS in Austria and worldwide. Similar to others, in our series the prevalence of TS was significantly higher in women than in men, while in contrast to other studies, the apical type of TS was detected most frequently. The similar clinical presentation of TS patients to the clinical picture of acute myocardial infarction demonstrates the importance of immediate coronary angiography for adequate differential diagnosis of TS. TS is not necessarily a benign disease due to cardiovascular complications as well as persistent WMAs with delayed recovery.

Activation induced morphological changes and integrin αIIbß3 activity of living platelets.

Platelets are essential in hemostasis. Upon activation they undergo a shape-change accompanied with receptor presentation. Atomic force microscopy (AFM) imaging and single molecule force spectroscopy (SMFS) were used as powerful tools for exploring morphological changes as well as receptor activities of platelets. Imaging time series was accomplished with and without fixation steps at the single platelet level. Hereby the response of mechanical stimulation of the platelet by the AFM cantilever tip was directly observed. We demonstrate that living and fixed platelets develop filopodia after a short activation time followed by their disappearance including cellular bleb formation. Thereafter a second filopodia formation (filopodia extrusion) was observed; those filopodia subsequently disappeared again, and finally platelets detached from the support due to cell death. We determined the influence of mechanical stress on the chronology of morphological changes of platelets and demonstrated shear force induced filopodia formation. Through recordings over several hours, topographical AFM images over the full platelet lifetime - from early activation up to apoptosis - are presented. SMFS measurements on living platelets allowed determining the activation state of the most prominent membrane receptor integrin αIIbß3 at all different phases of activation. αIIbß3 was fully activated, independent of the morphological state.

Platelet count predicts cardiovascular mortality in very elderly patients with myocardial infarction.

BACKGROUND: The prognosis of elderly patients with acute myocardial infarction (AMI) is poor, and information on specific risk factors remains scarce. The aim of our study was to assess the influence of platelet count on cardiovascular mortality in very elderly patients with acute myocardial infarction (≥ 85 years of age). METHODS: We identified 208 elderly AMI patients and compared the platelet count with 208 matched young AMI patients (≤ 65 years) and 208 matched intermediate age AMI patients (66-84 years) who derived from the same cohort. RESULTS: During a median follow-up of 4·7 years, 25% of patients (n = 156) died of cardiovascular causes (97 very elderly, 46 intermediate age and 13 young age patients). We detected a mean platelet count of 227G/l (SD ± 83) in very elderly AMI patients, of 236G/l (SD ± 78) in the intermediate AMI group and of 254G/l (SD ± 79) in 208 young AMI patients (ANOVA P = 0·002). We revealed a significant interaction between age and platelet count with regard to cardiovascular mortality (p for interaction = 0·014). Platelet count displayed a significant risk transformation from an independent risk factor for cardiovascular mortality in very elderly AMI patients (adj. hazard ratio (HR) per 1-SD increase 1·25;95%CI 1·02-1·54;P = 0·028), via displaying no association with mortality in the intermediate age group (P = 0·10), to a strong inverse association in young patients (adj. HR 0·36;95%CI 0·18-0·68;P = 0·002). CONCLUSION: Our study demonstrates an independent association between elevated platelet count and long-term cardiovascular mortality in the growing and vulnerable group of very elderly AMI patients. Nevertheless, the pathophysiologic mechanisms underlying this age-dependent effect have to be further clarified.

Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coronary intervention for acute ST-elevation myocardial infarction.

AIMS Pre-treatment with clopidogrel results in a reduction of ischaemic events in non-ST-elevation acute coronary syndromes. Data on upstream clopidogrel in the setting of primary percutaneous coronary intervention (PCI) are limited. The aim of this study was to investigate whether clopidogrel loading before arrival at the PCI centre may result in an improved outcome of primary PCI for ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS In a multicentre registry of acute PCI, 5955 patients undergoing primary PCI in Austria between January 2005 and December 2009 were prospectively enrolled. The patients consisted of two groups, a clopidogrel pre-treatment group (n = 1635 patients) receiving clopidogrel before arrival at the PCI centre and a peri-interventional clopidogrel group (n = 4320 patients) receiving clopidogrel at a later stage. Multiple logistic regression analysis including major confounding factors stratified by the participating centres was applied to investigate the effect of pre-treatment with clopidogrel on the in-hospital mortality. Additionally, two subgroups, with or without the use of GP IIb/IIIa antagonist therapy in the catheterization laboratory, were analysed. On univariate analysis, clopidogrel pre-treatment was associated with a reduced in-hospital mortality (3.4 vs. 6.1%, P< 0.01) after primary PCI. On multivariate analysis, clopidogrel pre-treatment remained an independent predictor of in-hospital mortality [odds ratio (OR) = 0.60, 95% confidence interval (CI) 0.35-0.99; P =0.048], especially in patients receiving additional GP IIb/IIIa antagonist therapy in the catheterization laboratory (OR = 0.40, 95% CI 0.19-0.83; P =0.01). CONCLUSION Clopidogrel pre-treatment before arrival at the PCI centre is associated with reduced mortality in a real world setting of primary PCI. These results strongly support the recommendation of clopidogrel treatment 'as soon as possible' in patients with STEMI undergoing pimary PCI.