A nationwide trend analysis on the usage of endomyocardial biopsy.

BACKGROUND: Endomyocardial biopsy (EMB) is a safe procedure performed in diagnostic work-up of cardiac disease. HYPOTHESIS: Data regarding temporal trends of total numbers, characteristics, in-hospital outcomes, and complications of patients undergoing EMB are sparse. METHODS: The nationwide German inpatient sample (2005-2019) was used for this analysis. Patient cases of EBM during the 5-year cycles from 2005 to 2009, 2010 to 2014, and 2015 to 2019 were compared, and temporal trends regarding total numbers and presumable major and minor EMB-associated complications were investigated. RESULTS: Overall, 67 745 EMB were performed in Germany 2005-2019. Total number of EMB increased from 3083 in 2005 to 5646 in 2019 (ß 0.40 [95% confidence interval [CI] 0.37-0.43], p < .001). Among these EMB, 19 083 (28.2%) were performed during the period 2005-2009, 22 867 (33.7%) 2010-2014, and 25 795 (38.1%) between 2015 and 2019. The proportion of patients aged ≥70 years was highest 2015-2019 (2005-2009: 9.3%; 2010-2014: 13.8%; 2015-2019: 16.1%, p < .001) and the most aggravated comorbidity profile (Charlson Comorbidity Index 2.25 ± 1.93; 2.67 ± 2.14; 3.01 ± 2.29, p < .001) was also detected 2015-2019. Major complications occurred less often in the period 2015-2019 compared to 2005-2009 (odds ratio [OR] 0.921 [95% CI 0.893-0.950], p < .001), whereas minor complications were more frequently observed between 2015 and 2019 (OR 1.067 [95% CI 1.042-1.093], p < .001). While a decrease in major complications was detected irrespective of age, an increase in minor complications was identified only in patients between 30-59 years. CONCLUSIONS: Annual numbers of EMB increased significantly in Germany 2005-2019. Patients who underwent EMB in recent years were older and showed an aggravated comorbidity profile accompanied by fewer major complications, underscoring safety of the procedure.

A multidisciplinary pulmonary embolism response team (PERT): first experience from a single center in Germany.

BACKGROUND: Over the last few years, the concept of multidisciplinary pulmonary embolism response teams (PERTs) has emerged to encounter the increasing variety and complexity in managing acute pulmonary embolism (PE). PURPOSE: To investigate PERT's composition and added clinical value in a university center in Germany. METHODS: Over 4 years (01/2019-11/2022), patients with confirmed PE were enrolled in a prospective single-center cohort study (PERT Mainz). We investigated the composition of PERT and compared, after propensity score matching, patients with acute PE before and after the initiation of PERT at our Medical University Centre. The primary outcome was in-hospital PE-related mortality. RESULTS: From 2019 to 2022, 88 patients with acute PE with a PERT decision were registered. Of those, 13 (14.8%) patients died during the in-hospital stay. Patients evaluated by a PERT had a median age of 68; 48.9% were females, and 21.7% suffered from malignancy. Right ventricular dysfunction was present in 76.1% of all patients. In total, 42.0% were classified as intermediate-high-risk PE and 11.4% as high-risk PE. First PERT contact mainly originated from emergency departments (33.3%) and intensive care units (30.0%), followed by chest pain units (21.3%) and regular wards (12.0%). The participation rate of medical specialties demonstrated that cardiologists (100%) or cardiac/vascular surgeons (98.6%) were included in almost all PERT consultations, followed by radiologists (95.9%) and anesthesiologists (87.8%). Compared to the PERT era, more patients in the pre-PERT era were classified as simplified pulmonary embolism severity index (sPESI) ≥ 1 (78.4% vs 71.6%) and as high-risk PE according to ESC 2019 guidelines (18.2% vs. 11.4%). In the pre-PERT era, low- and intermediate-low patients with PE received more frequently advanced reperfusion therapies such as systemic thrombolysis or surgical embolectomy compared to the PERT era (10.7% vs. 2.5%). Patients in the pre-PERT were found to have a considerably higher all-cause mortality and PE-related mortality rate (31.8% vs. 14.8%) compared to patients in the PERT era (22.7% vs. 13.6%). After propensity matching (1:1) by including parameters as age, sex, sPESI, and ESC risk classes, univariate regression analyses demonstrated that the PE management based on a PERT decision was associated with lower risk of all-cause mortality (OR, 0.37 [95%CI 0.18-0.77]; p = 0.009). For PE-related mortality, a tendency for reduction was observed (OR, 0.54 [95%CI 0.24-1.18]; p = 0.121). CONCLUSION: PERT implementation was associated with a lower risk of all-cause mortality rate in patients with acute PE. Large prospective studies are needed further to explore the impact of PERTs on clinical outcomes.

Temporal trends of case-fatality in patients undergoing dual-injection coronary chronic total occlusion recanalization.

AIMS: Recently, interventional techniques and material to treat chronic total occlusion (CTO) with percutaneous coronary intervention (PCI) have evolved significantly. Nevertheless, it is still unknown whether this progress improved treatment success and patients' outcome. In a nationwide sample, we sought to analyze trends of patients' characteristics, complications and in-hospital case-fatality of patients undergoing CTO revascularization in Germany. METHODS AND RESULTS: We analyzed data on characteristics, treatments, and in-hospital outcomes for all coronary artery disease (CAD) patients (ICD-code I25) undergoing dual-injection CTO recanalization (OPS procedural code: 8-839.9) in Germany from 2009 to 2020. Overall, 4,998,457 inpatients aged ≥ 18 years with diagnosis of CAD were treated in German hospitals in this period. Among these, 52,879 patients (1.1%) underwent CTO recanalization. Annual number of CTO PCIs increased from 1263 in 2009 to 6435 in 2020 (ß 3.48 [95% CI 3.44-3.52]; p < 0.001) in parallel with a significant decrease of case-fatality (2.2% in 2009 to 1.4% in 2020; ß - 0.60 [95% CI - 0.82 to - 0.39]; p < 0.001). Overall, 754 (1.4%) patients with CTO recanalization died during the in-hospital stay and in-hospital case-fatality grew exponentially with age (ß 0.82 [95% CI 0.73-0.90]; p < 0.001). Significant predictors of in-hospital case fatality with an OR > 3 were cancer, stroke, hemopericardium, acute renal failure, pulmonary embolism and shock. CONCLUSION: Annual number of CTO procedures performed in Germany increased from 2009 to 2020 with a concomitant anti-proportional decrease in the case-fatality. Our findings may help to draw more attention to predictors of in-hospital case fatality in patients hospitalized for CTO recanalization.

Impact of cardiac amyloidosis on outcomes of patients hospitalized with heart failure.

BACKGROUND: Amyloidosis is a multi-systemic disease potentially leading to failure of affected organs. We aimed to investigate prevalence and prognostic implications of cardiac amyloidosis of any etiology on outcomes of hospitalized patients with heart failure (HF) in Germany. METHODS: We analyzed data of the German nationwide inpatient sample (2005-2018) of patients hospitalized for HF (including myocarditis with HF and heart transplantation with HF). HF patients with amyloidosis (defined as cardiac amyloidosis [CA]) were compared with those HF patients without amyloidosis and impact of CA on outcomes was assessed. RESULTS: During this fourteen-year observational period 5,478,835 hospitalizations for HF were analyzed. Amyloidosis was coded in 5,407 HF patients (0.1%). CA prevalence was 1.87 hospitalizations per 100,000 German population. CA patients were younger (75.0[IQR 67.0-80.0]vs.79.0[72.0-85.0]years, p < 0.001), predominantly male (68.9%) and had a higher prevalence of cancer (14.8% vs. 3.6%, p < 0.001). Adverse in-hospital events including necessity of transfusions of blood constituents (7.1% vs. 5.4%, p < 0.001) and cardio-pulmonary resuscitation (CPR, 2.7% vs. 1.4%; p < 0.001) were more frequent in CA. CA was independently associated with acute kidney failure (OR 1.40 [95%CI 1.28-1.52], p < 0.001), CPR (OR 1.58 [95%CI 1.34-1.86], p < 0.001), intracerebral bleeding (OR 3.13 [95%CI 1.68-5.83], p < 0.001) and in-hospital mortality between the 5 and 8th decade of life, but in-hospital mortality was strongly influenced by cancer. CONCLUSIONS: CA was identified as an independent risk factor for complications and in-hospital mortality in HF patients, whereby it has to be mentioned that amyloidosis subtypes could not differentiated in the present study. Physicians should be aware of this issue concerning treatments and monitoring of CA-patients.

TNF-α blockade may lead to improvement of vascular function in psoriasis patients.

Psoriasis is one of the most common chronic inflammatory skin diseases and at the same time a risk factor for cardiovascular disease. Interleukin-17A (IL-17A)-mediated inflammation in psoriasis may lead to vascular dysfunction. This study aimed at investigating whether anti-inflammatory treatment by tumor necrosis factor (TNF)-α blockade alters vascular function in psoriasis patients. A total of 11 patients with psoriasis who underwent treatment with either adalimumab (n = 8) or etanercept (n = 3), 10 healthy control individuals and 14 patients with coronary artery disease (CAD) were included in this study. Treatment response was assessed using the Psoriasis Area and Severity Index (PASI) score. Endothelial reactivity and resting endothelium-dependent vascular tone were assessed by ultrasound measurement of flow-mediated dilation (FMD) and low-flow-mediated constriction (l-FMC), respectively. FMD was slightly impaired in psoriasis patients compared to healthy controls. Anti-TNF-α treatment did not significantly change FMD levels. Psoriasis patients showed a trend towards increased baseline vascular activity compared to healthy controls. Anti-TNF-α treatment significantly improved l-FMC in psoriasis patients. Noteworthy, both FMD and l-FMC in psoriasis patients were comparable to those in patients with CAD; however, an important influence of age differences between the groups or co-existent classical cardiovascular risk factors on FMD and l-FMC cannot be ruled out by our small study. The results suggest that anti-inflammatory treatment with TNF-α blockade improves vascular function in patients with psoriasis, mainly by altering baseline vascular tone. Further studies will be necessary to establish the potentially protective impact of anti-inflammatory therapy on vascular function in patients with chronic inflammatory diseases.

Effectiveness of a Real-Time X-ray Dosimetry Monitor in Reducing Radiation Exposure in Coronary Procedures: The ESPRESSO-Raysafe Randomized Trial.

Background-Several methods to reduce radiation exposure in the setting of coronary procedures are available on the market, and we previously showed that additional radiation shields reduce operator exposure during radial interventions. We set out to examine the efficacy of real-time personal dosimetry monitoring in a real-world setting of radial artery catheterization. Methods and Results-In an all-comer prospective, parallel study, consecutive coronary diagnostic and intervention procedures were performed with the use of standard radiation shield alone (control group) or with the addition of a real-time dosimetry monitoring system (Raysafe, Billdal, Sweden, monitoring group). The primary outcome was the difference in exposure of the primary operator among groups. Additional endpoints included patient, nurse, second operator exposure and fluoroscopy time. A total of 700 procedures were included in the analysis (n = 369 in the monitoring group). There were no differences among groups in patients' body mass index (p = 0.232), type of procedure (intervention vs. diagnostic, p = 0.172), and patient sex (p = 0.784). Fluoroscopy time was shorter in the monitoring group (5.6 (5.1-6.2) min vs. 7.0 (6.1-7.7) min, p = 0.023). Radiation exposure was significantly lower in the monitoring group for the patient (135 (115-151) µSv vs. 208 (176-245) µSv, p < 0.0001) but not for the first operator (9 (7-11) µSv vs. 10 (8-11), p = 0.70) and the assistant (2 (1-2) µSv vs. 2 (1-2) µSv, p = 0.121). Conclusions-In clinical daily practice, the use of a real-time dosimetry monitoring device reduces patient radiation exposure and fluoroscopy time without an effect on operator radiation exposure.

Coronary In-Stent Restenosis: Predictors and Treatment.

BACKGROUND: Despite the use of modern drug-eluting stents (DES), in-stent restenosis (ISR) may still occur in as many as 2-10% of percutaneous coronary interventions (PCI) in certain lesion/patient subsets. ISR causes increased morbidity after stent implantation; acute myocardial infarction is a frequent correlate to a clinical ISR, arising in 5-10% of cases. Compared to de novo stenosis, patients with ISR also present more frequently with symptoms of unstable angina pectoris (45% versus 61%). In this article, we discuss the risk factors for ISR and the corresponding diagnostic measures and effective treatment strategies. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed, with special attention to current international guidelines and specialist society recommendations. RESULTS: The type of implanted stent, the presence of diabetes mellitus, previous bypass surgery, and small vessel caliber are predictors for ISR. In their guidelines, the European specialist societies (ESC/EACTS) recommend repeated PCI with DES implantation or drug-coated balloon (DCB) angioplasty as the methods of choice for the treatment of ISR. This approach is supported by evidence from meta-analyses. The RIBS-IV trial showed that revascularization treatment of the target lesion is needed less often after everolimus-eluting stent (EES) implantation than after DCB dilatation (11 [7.1%] versus 24 [15.6%]; p = 0.015; hazard ratio: 0.43; 95% confidence interval: [0.21; 0.87]). CONCLUSION: Because the pathogenesis of ISR is multifactorial, differentiated risk stratification is necessary. The identification of patient-, stent-, and lesion-related predictors is particularly important, as the most effective way to combat ISR is to prevent it.

Efficacy and Safety of Revacept, a Novel Lesion-Directed Competitive Antagonist to Platelet Glycoprotein VI, in Patients Undergoing Elective Percutaneous Coronary Intervention for Stable Ischemic Heart Disease: The Randomized, Double-blind, Placebo-Controlled ISAR-PLASTER Phase 2 Trial.

Importance: The assessment of new antithrombotic agents with a favorable safety profile is clinically relevant. Objective: To test the efficacy and safety of revacept, a novel, lesion-directed antithrombotic drug, acting as a competitive antagonist to platelet glycoprotein VI. Design, Setting, and Participants: A phase 2 randomized clinical trial; patients were enrolled from 9 centers in Germany from November 20, 2017, to February 27, 2020; follow-up ended on March 27, 2020. The study included patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous coronary intervention (PCI). Interventions: Single intravenous infusion of revacept, 160 mg, revacept, 80 mg, or placebo prior to the start of PCI on top of standard antithrombotic therapy. Main Outcomes and Measures: The primary end point was the composite of death or myocardial injury, defined as an increase in high-sensitivity cardiac troponin to at least 5 times the upper limit of normal within 48 hours from randomization. The safety end point was bleeding type 2 to 5 according to the Bleeding Academic Research Consortium criteria at 30 days. Results: Of 334 participants (median age, 67.4 years; interquartile range, 60-75.1 years; 253 men [75.7%]; and 330 White participants [98.8%]), 120 were allocated to receive the 160-mg dose of revacept, 121 were allocated to receive the 80-mg dose, and 93 received placebo. The primary end point showed no significant differences between the revacept and placebo groups: 24.4%, 25.0%, and 23.3% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .98). The high dose of revacept was associated with a small but significant reduction of high-concentration collagen-induced platelet aggregation, with a median 26.5 AU × min (interquartile range, 0.5-62.2 AU × min) in the revacept, 160 mg, group; 43.5 AU × min (interquartile range, 22.8-99.5 AU × min) in the revacept, 80 mg, group; and 41.0 AU × min (interquartile range, 31.2-101.0 AU × min) in the placebo group (P = .02), while adenosine 5'-diphosphate-induced aggregation was not affected. Revacept did not increase Bleeding Academic Research Consortium type 2 or higher bleeding at 30 days compared with placebo: 5.0%, 5.9%, and 8.6% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .36). Conclusions and Relevance: Revacept did not reduce myocardial injury in patients with stable ischemic heart disease undergoing percutaneous coronary intervention. There were few bleeding events and no significant differences between treatment arms. Trial Registration: ClinicalTrials.gov Identifier: NCT03312855.

Impact of Psoriasis on Mortality Rate and Outcome in Myocardial Infarction.

Background Psoriasis is a frequent chronic inflammatory cytokine-mediated skin disease and was identified to be an independent risk factor for the occurrence of myocardial infarction (MI). However, data about the impact of psoriasis on mortality and other in-hospital adverse events in the setting of MI are sparse and inconsistent. Methods and Results The nationwide German inpatient sample of the years 2005 to 2016 was used for statistical analysis. Hospitalized patients with MI were stratified for the presence of psoriasis and the impact of psoriasis on in-hospital events was investigated. Overall, 3 307 703 patients with MI (37.6% females, 56.8% aged ≥70 years) were treated in Germany (2005-2016); among them 9028 (0.3%) were diagnosed with psoriasis. Patients with MI with psoriasis were significantly younger (68.0 [58.0-76.0] versus 73.0 [62.0-81.0] years; P<0.001) and showed significant lower in-hospital case-fatality rate (7.1% versus 12.4%; P<0.001), confirmed in the regression (odds ratio, 0.68; 95% CI, 0.63-0.74; P<0.001) adjusted for age, sex, and comorbidities. They more frequently revealed cardiovascular risk factors such as arterial hypertension (58.9% versus 55.0%; P<0.001), hyperlipidemia (44.4% versus 38.6%; P<0.001), smoking (14.3% versus 7.4%; P<0.001), diabetes mellitus (34.8% versus 30.4%; P<0.001) or obesity (17.9% versus 9.3%; P<0.001). While the rate of percutaneous coronary intervention (41.4 versus 42.0%; P=0.223) was comparable between both groups, coronary bypass surgery was more often performed in patients with MI with psoriasis (7.7% versus 4.7%; P<0.001). Conclusions Overall, only 0.3% of all MI cases were diagnosed with psoriasis, and patients with MI with psoriasis were in median 5 years younger than patients with MI without psoriasis. Psoriasis seems to enhance the prevalence of classical cardiovascular risk factors and might therefore explain the earlier time point for MI. Our data also showed in turn a lower in-hospital mortality rate in patients with MI with psoriasis, presumably driven by younger age.

Safety of transradial and transfemoral left ventricular compared with transfemoral right ventricular endomyocardial biopsy.

AIMS: With the present study, we sought to determine the safety of three different endomyocardial biopsy (EMB) access routes in 514 patients admitted for diagnostic workup of heart failure of unknown aetiology. METHODS AND RESULTS: In this retrospective monocentric cohort study, we analysed 514 consecutive patients with heart failure without evidence of significant coronary artery disease or valvular disease undergoing EMB between November 2013 and December 2018, stratified in three access route groups: transradial arterial left ventricular (LV-)EMB (323 patients), transfemoral LV-EMB (138 patients), and transfemoral right ventricular (RV-)EMB (53 patients). Patients undergoing selective transradial LV-EMB were older compared with patients undergoing selective transfemoral LV-EMB or RV-EMB [transradial LV-EMB: 56.0 (45.0/64.0) vs. transfemoral LV-EMB: 53 (42.5/64.5), P = 0.455; transradial LV-EMB: 56 (45.0/64.0) vs. RV-EMB: 53 (42.5/64), P = 0.695] and presented more often in New York Heart Association-functional class III and IV. A total of eight major complications including permanent atrioventricular block requiring pacemaker implantation, pericardial tamponade necessitating pericardiocentesis, stroke and transient cerebral ischaemic attack as well as severe valvular damage, vascular access site complications, and ventricular fibrillation were documented with no significant differences between the groups (8/514, 1.5%). Minor complications such as transient chest pain, non-sustained electrocardiogram abnormalities, and transient atrioventricular block were rare and equally distributed between groups. CONCLUSIONS: Transradial LV-EMB is a safe procedure for experienced radial operators and non-inferior compared with transfemoral LV-EMB and RV-EMB. An accurate peri-procedural and post-procedural monitoring and follow-up care should be recommended for all patients undergoing this procedure in order to identify potential complications.

Association of transcatheter direct mitral annuloplasty with acute anatomic, haemodynamic, and clinical outcomes in severe mitral valve regurgitation.

AIMS: Several approaches for transcatheter mitral valve repair for functional mitral valve regurgitation are established. Interventional direct annuloplasty is a novel trans-venous, trans-septal approach. While feasibility was proven recently, knowledge on its influence on cardiac dimensions, pressures, biomarkers, and clinical outcomes is sparse. METHODS AND RESULTS: Patients consecutively treated with direct annuloplasty-only procedures between December 2015 and April 2018 were included in this monocentric analysis. Echocardiographic measurements, biomarker levels, clinical status [New York Heart Association (NYHA) class and 6 min walk test] were assessed at baseline, at discharge, and at a 30 day follow-up. Overall, 18 patients (in mean 77.0 ± 7.4 years, 44.4% women) with initially all high-grade mitral valve regurgitation (MR) were included in this study. Procedural success rate was high (94.4%) without severe complications. Direct annuloplasty resulted in MR-reduction (post-procedural-MR mild or no/trace: 72.2%) and the proportion of patients with severe dyspnoea (NYHA III/IV) was reduced (88.9% vs. 50%, P = 0.008). Clinical results were associated with a relevant diminution of left atrial volumes (-16.5%, P < 0.001) and cardiac pressures [left atrial pressure (-32.3%, P = 0.019) and systolic pulmonary arterial pressure (PAP, -15.8%, P = 0.025)]. Patients with lower baseline levels of PAP (P = 0.022) as well as elevated highly sensitive troponin (P = 0.034) were more likely to archive clinical benefit (improvement in NYHA class ≥1 grade) after 1 month, which could not be correlated with the grade of MR-reduction. CONCLUSIONS: Transcatheter mitral valve repair by direct annuloplasty results in a relevant reduction of intracardiac pressures, left atrial volumes, dyspnoea, and MR. Lower PAP and higher troponin values at baseline could be associated to dyspnoea reduction.

Coronary Stent Thrombosis- Predictors and Prevention.

BACKGROUND: Stent thrombosis (ST) is a dreaded complication after stent implantation and is associated with a mortality between 5% and 45%. The mechanisms by which ST arises are complex. Because of the seriousness of this situation, all phy - sicians should have at least basic knowledge of it. In this article, we present the risk factors for ST and discuss some innovative approaches to its treatment. METHODS: This review is based on pertinent articles retrieved by a selective search in PubMed, and on current international guidelines and expert recommendations. RESULTS: The frequency of ST has been markedly lowered by technical advances in coronary stenting and by the implementation of modern implantation techniques, including the introduction of coverage with dual antiplatelet therapy (DAPT). Both patient-related risk factors and procedural aspects can elevate the risk of ST. The independent risk factors for ST include premature termination of DAPT (hazard ratio [HR] 26.8; 95% confidence interval [8.4; 85.4]; p <0.0001), malignant disease (odds ratio [OR]: 17.45; [4.67; 65.26]; p <0.0001), and diabetes mellitus (OR: 3.14; [1.33; 7.45]; p = 0.0093). In comparison to angiographically guided procedures, the use of intracoronary imaging techniques in patients with acute coronary syndrome lowers the frequency of ST (0.6% versus 1.2%; p = 0.005). These techniques enable the detection of many findings in the coronary arteries that are associated with the development of ST. In such cases, countermeasures such as secondary stent dilatation or prolongation of DAPT can help prevent ST. CONCLUSION: As the pathophysiology of ST is multifactorial, research in this area presents a special challenge. Prospective clinical trials will be needed to determine whether the systematic use of imaging techniques can lower the frequency of ST.

Effectiveness of additional X-ray protection devices in reducing scattered radiation in radial intervention: the ESPRESSO randomised trial.

AIMS: We aimed to examine the impact of three different radiation protection devices in a real-world setting of radial artery catheterisation. METHODS AND RESULTS: In an all-comer randomised trial, consecutive coronary radial diagnostic and intervention procedures were assigned in a 1:1:1 ratio to shield-only protection (shield group), shield and overlapping 0.5 mm Pb panel curtain (shield+curtain group) or shield, curtain and additional 75x40 cm, 0.5 mm Pb drape placed across the waist of the patient (shield+curtain+drape group). A total of 614 radial procedures were randomised (n=193 shield, n=220 shield+curtain, n=201 shield+curtain+drape). There were no differences among the groups in patient or procedural characteristics. The primary endpoint (relative exposure ratio between the operators' exposure in µSv and the patient's exposure, dose area product in cGy·cm2) was significantly lower in the shield+curtain+drape group for both the first operator (20% reduction vs shield, 16% vs shield+curtain, p=0.025) and the assistant (39% reduction vs shield, 25% vs shield+curtain, p=0.009). CONCLUSIONS: The use of an additional drape reduced the radiation exposure of both the first operator and the second operator during routine radial procedures; a shield-attached curtain alone was only partially effective. ClinicalTrials.gov identifier: NCT03634657

Impact of renal function on clinical outcomes after PCI in ACS and stable CAD patients treated with ticagrelor: a prespecified analysis of the GLOBAL LEADERS randomized clinical trial.

BACKGROUND: Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF. METHODS: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m2). RESULTS: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35-1.98, padj = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61-1.11, p = 0.192, pint = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71-1.71, p = 0.656, pint = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (pint = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (pint = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF. CONCLUSIONS: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy. CLINICAL TRIAL REGISTRATION: The trial has been registered with ClinicalTrials.gov, number NCT01813435.

Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study.

AIMS: In a randomized, parallel, blinded study, we investigate the impact of clopidogrel, prasugrel, or ticagrelor on peripheral endothelial function in patients undergoing stenting for an acute coronary syndrome. METHODS AND RESULTS: The primary endpoint of the study was the change in endothelium-dependent flow-mediated dilation (FMD) following stenting. A total of 90 patients (age 62 ± 9 years, 81 males, 22 diabetics, 49 non-ST elevation myocardial infarctions) were enrolled. There were no significant differences among groups in any clinical parameter. Acutely before stenting, all three drugs improved FMD without differences between groups (P = 0.73). Stenting blunted FMD in the clopidogrel and ticagrelor group (both P < 0.01), but not in the prasugrel group. During follow-up, prasugrel was superior to clopidogrel [mean difference 2.13, 95% confidence interval (CI) 0.68-3.58; P = 0.0047] and ticagrelor (mean difference 1.57, 95% CI 0.31-2.83; P = 0.0155), but this difference was limited to patients who received the study therapy 2 h before stenting. Ticagrelor was not significantly superior to clopidogrel (mean difference 0.55, 95% CI -0.73 to 1.82; P = 0.39). No significant differences were seen among groups for low-flow-mediated dilation. Plasma interleukin (IL)-6 (P = 0.02 and P = 0.01, respectively) and platelet aggregation reactivity in response to adenosine diphosphate (P = 0.002 and P = 0.035) were lower in the prasugrel compared to clopidogrel and ticagrelor group. CONCLUSION: As compared to ticagrelor and clopidogrel, therapy with prasugrel in patients undergoing stenting for an acute coronary syndrome is associated with improved endothelial function, stronger platelet inhibition, and reduced IL-6 levels, all of which may have prognostic implications. This effect was lost in patients who received the study medication immediately after stenting. EUDRACT-NO: 2011-005305-73.

Short-term e-cigarette vapour exposure causes vascular oxidative stress and dysfunction: evidence for a close connection to brain damage and a key role of the phagocytic NADPH oxidase (NOX-2).

AIMS: Electronic (e)-cigarettes have been marketed as a 'healthy' alternative to traditional combustible cigarettes and as an effective method of smoking cessation. There are, however, a paucity of data to support these claims. In fact, e-cigarettes are implicated in endothelial dysfunction and oxidative stress in the vasculature and the lungs. The mechanisms underlying these side effects remain unclear. Here, we investigated the effects of e-cigarette vapour on vascular function in smokers and experimental animals to determine the underlying mechanisms. METHODS AND RESULTS: Acute e-cigarette smoking produced a marked impairment of endothelial function in chronic smokers determined by flow-mediated dilation. In mice, e-cigarette vapour without nicotine had more detrimental effects on endothelial function, markers of oxidative stress, inflammation, and lipid peroxidation than vapour containing nicotine. These effects of e-cigarette vapour were largely absent in mice lacking phagocytic NADPH oxidase (NOX-2) or upon treatment with the endothelin receptor blocker macitentan or the FOXO3 activator bepridil. We also established that the e-cigarette product acrolein, a reactive aldehyde, recapitulated many of the NOX-2-dependent effects of e-cigarette vapour using in vitro blood vessel incubation. CONCLUSIONS: E-cigarette vapour exposure increases vascular, cerebral, and pulmonary oxidative stress via a NOX-2-dependent mechanism. Our study identifies the toxic aldehyde acrolein as a key mediator of the observed adverse vascular consequences. Thus, e-cigarettes have the potential to induce marked adverse cardiovascular, pulmonary, and cerebrovascular consequences. Since e-cigarette use is increasing, particularly amongst youth, our data suggest that aggressive steps are warranted to limit their health risks.

Endothelial Function Assessed by Digital Volume Plethysmography Predicts the Development and Progression of Type 2 Diabetes Mellitus.

Background Endothelial dysfunction is a consequence of type 2 diabetes mellitus, but it is unclear whether endothelial dysfunction of conductance versus resistance vessels may also precede type 2 diabetes mellitus development. Methods and Results In a population-based cohort of 15 010 individuals from the GHS (Gutenberg Health Study) (aged 35-74 years at enrollment in 2007-2012), we identified 1610 cases of incident pre-diabetes mellitus and 386 cases of incident type 2 diabetes mellitus by hemoglobin A1c (HbA1c) and/or medical history between 2012 and 2017. Endothelial function of conductance and resistance vessels was measured by flow-mediated dilation and digital volume plethysmography-derived reactive hyperemia index, respectively. Multivariable regression modeling was used to estimate ß coefficients of HbA1c levels at follow-up and relative risks of incident (pre-)diabetes mellitus. Reactive hyperemia index was independently associated with HbA1c after multivariable adjustment for baseline HbA1c, sex, age, socioeconomic status, arterial hypertension, waist/height ratio, pack-years of smoking, non-high-density lipoprotein/high-density lipoprotein ratio, physical activity, family history of myocardial infarction/stroke, prevalent cardiovascular disease, medication use, and C-reactive protein (ß=-0.020; P=0.0029). The adjusted relative risk per SD decline in reactive hyperemia index was 1.08 (95% CI, 1.02-1.15; P=0.012) for incident pre-diabetes mellitus and 1.16 (95% CI, 1.01-1.34; P=0.041) for incident type 2 diabetes mellitus. Flow-mediated dilation independently increased the relative risk for developing pre-diabetes mellitus by 8% (95% CI, 1.02-1.14; P=0.012), but it was not independently associated with incident type 2 diabetes mellitus (relative risk, 1.01; 95% CI, 0.86-1.19; P=0.92) and with HbA1c (ß=-0.003; P=0.59). Conclusions Endothelial dysfunction of resistance rather than conductance vessels may precede the development of (pre-)diabetes mellitus. Assessment of endothelial function by digital volume plethysmography may help to identify subjects at risk for development of type 2 diabetes mellitus.

Advanced Protocol for Three-Dimensional Transesophageal Echocardiography Guidance Implementing Real-Time Multiplanar Reconstruction for Transcatheter Mitral Valve Repair by Direct Annuloplasty.

Transcatheter direct annuloplasty has been introduced as a novel interventional treatment option for severe mitral valve regurgitation. Until now, only one direct annuloplasty device (Edwards Cardioband) has been commercially available, being implanted in more than 250 patients worldwide. Yet this procedure poses greater challenges regarding optimal fluoroscopic and echocardiographic guidance compared with edge-to-edge repair: correct localization and orientation of the anchors upon penetration into the fibrous mitral annulus tissue and the basal left ventricular myocardium are preconditions for an optimal result and essential to avoid damage of the neighboring structures (atrioventricular node, circumflex artery, coronary sinus). Real-time single-beat multiplanar reconstruction has become available as an additional imaging tool for three-dimensional transesophageal echocardiography in most recent echo machines. In this review, we introduce a three-dimensional transesophageal echocardiography-based imaging protocol implementing real-time multiplanar reconstruction for transcatheter direct annuloplasty procedures, which optimizes and also simplifies echocardiographic guidance during the implantation. The advanced echocardiographic protocol might also help to expedite implantation times and potentially increase the safety of the procedure. In this "how-to" article, we describe in detail this novel approach for optimized guidance and compare its advantages and challenges to "conventional" echocardiographic imaging for transcatheter mitral valve repair.

Effectiveness of additional X-ray protection devices in reducing Scattered radiation in radial interventions: protocol of the ESPRESSO randomised trial.

BACKGROUND: A number of devices have been developed to minimise operator radiation exposure in the setting of cardiac catheterisation. The effectiveness of these devices has traditionally been explored in transfemoral coronary procedures; however, less is known for the transradial approach. We set out to examine the impact of three different radiation protection devices in a real-world setting. METHODS AND DESIGN: Consecutive coronary diagnostic and intervention procedures are randomised in a 1:1:1 ratio to a shield-only protection (shield group), shield and overlapping 0.5 mm Pb panel curtain (curtain group) or shield, curtain and additional 75×40 cm, 0.5 mm Pb drape placed across the waist of the patient (drape group).The primary outcome is the difference in relative exposure of the primary operator among groups. Relative exposure is defined as the ratio between operator's exposure (E in µSv) and patient exposure (dose area product in cGy·cm2). ETHICS AND DISSEMINATION: The protocol complies with good clinical practice and the ethical principles described in the Declaration of Helsinki and is approved by the local ethics committee. The results of the trial will be published as original article(s) in medical journals and/or as presentation at congresses. TRIAL REGISTRATION NUMBER: NCT03634657.