0000000000003239
AUTHOR
Stephan Baldus
Centre procedural volume and adverse in‐hospital outcomes in patients undergoing percutaneous transvenous edge‐to‐edge mitral valve repair usingMitraClip® inGermany
AIMS The number of transcatheter mitral valve repair (TMVr) procedures has increased substantially during the last years. A better understanding of the relationship between hospital volume of transcatheter transvenous mitral valve repairs using MitraClip® and patient outcomes may provide information for future policy decisions to improve patient management. METHODS AND RESULTS We analysed patient characteristics and in-hospital outcomes for all TMVr procedures using MitraClip® performed in Germany from 2011 to 2017. Hospitals were stratified according to centre volumes and patients were compared for baseline characteristics and adverse in-hospital events. Overall, 24 709 inpatients were tre…
Diagnostic and prognostic performance of myeloperoxidase plasma levels compared with sensitive troponins in patients admitted with acute onset chest pain.
Background— Activation of leukocytes with release of myeloperoxidase (MPO) has been linked to acute coronary disease. To date, studies investigating the diagnostic and prognostic performance of circulating MPO in patients with chest pain (CP) are mainly retrospective, of low size, and lack a cut-off value for MPO. Herein, we prospectively assess the diagnostic and prognostic properties of MPO compared with sensitive troponin I (sTNI) in patients admitted to the emergency room with CP. Methods and Results— One thousand, eight hundred and eighteen consecutive patients (mean age, 61.4±13.5 years; 33.6% female) admitted for CP underwent determination of MPO, sTnI, and B-natriuretic peptide pla…
Impact of Proportionality of Secondary Mitral Regurgitation on Outcome After Transcatheter Mitral Valve Repair
The purpose of this paper was to evaluate the impact of proportionality of secondary mitral regurgitation (SMR) in a large real-world registry of transcatheter edge-to-edge mitral valve repair (TMVr) BACKGROUND: Differences in the outcomes of recent randomized trials of TMVr for SMR may be explained by the proportionality of SMR severity to left ventricular (LV) volume.The ratio of pre-procedural effective regurgitant orifice area (EROA) to LV end-diastolic volume (LVEDV) was retrospectively assessed in patients undergoing TMVr for severe SMR between 2008 and 2019 from the EuroSMR registry. A recently proposed SMR proportionality scheme was adapted to stratify patients according to EROA/LVE…
1210Long-term follow-up in the German TRAnscatheter mitral valve Interventions (TRAMI) registry: survival and predictors of mortality
P6456Neopterin for risk stratification of patients with acute chest pain
Impact of Right Ventricular Dysfunction on Outcomes After Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation
OBJECTIVES This study sought to assess the impact of right ventricular dysfunction (RVD) as defined by impaired right ventricular-to-pulmonary artery (RV-PA) coupling, on survival after edge-to-edge transcatheter mitral valve repair (TMVR) for severe secondary mitral regurgitation (SMR). BACKGROUND Conflicting data exist regarding the benefit of TMVR in severe SMR. A possible explanation could be differences in RVD. METHODS Using data from the EuroSMR (European Registry on Outcomes in Secondary Mitral Regurgitation) registry, this study compared the characteristics and outcomes of SMR patients undergoing TMVR, according to their RV-PA coupling, assessed by tricuspid annular plane systolic e…
GDF-15 predicts cardiovascular events in acute chest pain patients
Background Treatment of patients presenting with possible acute myocardial infarction (AMI) is based on timely diagnosis and proper risk stratification aided by biomarkers. We aimed at evaluating the predictive value of GDF-15 in patients presenting with symptoms suggestive of AMI. Methods Consecutive patients presenting with suspected AMI were enrolled in three study centers. Cardiovascular events were assessed during a follow-up period of 6 months with a combined endpoint of death or MI. Results From the 1818 enrolled patients (m/f = 1208/610), 413 (22.7%) had an acute MI and 63 patients reached the combined endpoint. Patients with MI and patients with adverse outcome had higher GDF-15 le…
Troponin I Assay for Identification of a Significant Coronary Stenosis in Patients with Suspected Acute Myocardial Infarction and Wide QRS Complex
Background Common ECG criteria such as ST-segment changes are of limited value in patients with suspected acute myocardial infarction (AMI) and bundle branch block or wide QRS complex. A large proportion of these patients do not suffer from an AMI, whereas those with ST-elevation myocardial infarction (STEMI) equivalent AMI benefit from an aggressive treatment. Aim of the present study was to evaluate the diagnostic information of cardiac troponin I (cTnI) in hemodynamically stable patients with wide QRS complex and suspected AMI. Methods In 417 out of 1818 patients presenting consecutively between 01/2007 and 12/2008 in a prospective multicenter observational study with suspected AMI a pro…
Homoarginine Levels are Regulated by L-Arginine: Glycine Amidinotransferase and Affect Stroke Outcome: Results from Human and Murine Studies
Background— Endogenous arginine homologues, including homoarginine, have been identified as novel biomarkers for cardiovascular disease and outcomes. Our studies of human cohorts and a confirmatory murine model associated the arginine homologue homoarginine and its metabolism with stroke pathology and outcome. Methods and Results— Increasing homoarginine levels were independently associated with a reduction in all-cause mortality in patients with ischemic stroke (7.4 years of follow-up; hazard ratio for 1-SD homoarginine, 0.79 [95% confidence interval, 0.64–0.96]; P =0.019; n=389). Homoarginine was also independently associated with the National Institutes of Health Stroke Scale+age score …
Extensive characterization of the human DDAH1 transgenic mice
Abstract Purpose of the research Overexpression of the human dimethylarginine dimethylaminohydrolase type 1 (hDDAH1) gene was reported to have beneficial cardiovascular effects in mice. To date, it is unclear whether these effects are related to enhanced metabolic clearance of asymmetric dimethylarginine (ADMA) and l - N G -mono-methyl- l -arginine ( l -NMMA) or increased DDAH1 expression and activity in cardiovascular tissues of hDDAH1 transgenic mice. Principal results DDAH activity (DDAH1 + DDAH2) was found to be markedly increased in aortic and heart tissues but unaltered in liver and kidney tissues of hDDAH1 transgenic as compared to wild-type (WT) mice. In WT mice, DDAH activity was m…
Sex-Related Clinical Characteristics and Outcomes of Patients Undergoing Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.
OBJECTIVES The authors sought to assess sex-based differences in characteristics and outcomes of patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) for secondary mitral regurgitation (SMR). BACKGROUND Subgroup analysis from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart��Failure Patients with Functional Mitral Regurgitation) trial indicated potential sex-related differences in outcomes after TMVR. The impact of sex on results after TMVR in a real-world setting is unknown. METHODS The authors assessed clinical outcomes and echocardiographic parameters in women and men undergoing TMVR for SMR between 2008 and 2018 who were …
Estimation of Values below the Limit of Detection of a Contemporary Sensitive Troponin I Assay Improves Diagnosis of Acute Myocardial Infarction
Abstract BACKGROUND The limit of detection (LoD) is the minimal amount of a substance that can be consistently detected. In the diagnosis of acute myocardial infarction (AMI) many patients present with troponin concentrations below the LoD of contemporary sensitive cardiac troponin I (cs-cTnI) assays. These censored values below the LoD influence the diagnostic performance of these assays compared to highly sensitive cTnI (hs-cTnI) assays. Therefore we assessed the impact of a new approach for interpolation of the left-censored data of a cs-cTnI assay in the evaluation of patients with suspected AMI. METHODS Our posthoc analysis used a real world cohort of 1818 patients with suspected MI. D…
Prognostic information of glycogen phosphorylase isoenzyme BB in patients with suspected acute coronary syndrome.
Early and adequate risk stratification is essential in patients with suspected acute coronary syndrome (ACS). The aim of the present study was to investigate whether glycogen phosphorylase BB (GPBB) could add prognostic information in the context of contemporary sensitive troponin I determination and B-type natriuretic peptide (BNP). Patients with suspected ACS were consecutively enrolled at 3 German study centers from January 2007 through December 2008. Troponin I, GPBB, and BNP were determined at admission. Follow-up information on the combined end point of death, myocardial infarction, revascularization, and hospitalization owing to a cardiovascular cause was obtained 6 months after enro…
Cardiac Troponins for the Diagnosis of Acute Myocardial Infarction in Chronic Kidney Disease
Background Patients with chronic kidney disease ( CKD ) are at high risk of myocardial infarction. Cardiac troponins are the biomarkers of choice for the diagnosis of acute myocardial infarction ( AMI ) without ST ‐segment elevation ( NSTE ). In patients with CKD , troponin levels are often chronically elevated, which reduces their diagnostic utility when NSTE ‐ AMI is suspected. The aim of this study was to derive a diagnostic algorithm for serial troponin measurements in patients with CKD and suspected NSTE ‐ AMI . Methods and Results Two cohorts, 1494 patients from a prospective cohort study with high‐sensitivity troponin I (hs‐ cTnI ) measurements and 7059 cases from a clinical registr…
Tricuspid valve repair with the Cardioband system: two-year outcomes of the multicentre, prospective TRI-REPAIR study
AIMS: Tricuspid regurgitation (TR) is associated with high morbidity and mortality rates with limited treatment options. We report one- and two-year outcomes of the Cardioband tricuspid valve reconstruction system in the treatment of ≥moderate functional TR in the TRI-REPAIR study. METHODS AND RESULTS: Thirty patients were enrolled in this single-arm, multicentre, prospective study. Patients were evaluated as having ≥moderate, symptomatic functional TR and deemed inoperable due to unacceptable surgical risk. Clinical, functional, and echocardiographic data were prospectively collected up to two years (mean duration 604±227 days). At baseline, 83% were in NYHA Class III-IV, and the mean LVEF…
Impact of left atrial diameter on outcome in patients undergoing edge-to-edge mitral valve repair: results from the German TRAnscatheter Mitral valve Interventions registry (TRAMI)
Abstract Background Left atrium (LA) dimension is a marker of disease severity and outcome in primary and secondary mitral regurgitation. In transcatheter mitral valve repair LA enlargement might additionally impact on device handling and technical success through an altered anatomy and atrial annular dilatation. Methods Data from the multicenter German transcatheter mitral valve intervention registry “TRAMI” were used to analyse the association of baseline LA diameter by tertiles and efficacy, safety and long-term clinical outcome in patients undergoing edge-to-edge repair with the MitraClip. Results In 520 of 843 patients prospectively enrolled in TRAMI baseline LA diameter were reported …
Clinical outcome of critically ill, not fully recompensated, patients undergoing MitraClip therapy
Aims As periprocedural risk is low, MitraClip implantation is often performed in critically ill, not fully recompensated patients, who are in NYHA functional class IV at the time of the procedure, to accelerate convalescence. We herein sought to evaluate the procedural and 30-day outcome of this patient group. Methods and results A total of 803 patients undergoing MitraClip implantation were included in the German Mitral Valve Registry, and 30-day outcomes were prospectively assessed. Patients were separated based on NYHA functional class [(NYHA IV (n = 143), III (n = 572), and I/II (n = 88)]. No difference was noted in co-morbities and echocardiographic parameters of LV function between gr…
Copeptin Improves Early Diagnosis of Acute Myocardial Infarction
ObjectivesEarly identification of myocardial infarction in chest pain patients is crucial to identify patients at risk and to maintain a fast treatment initiation.BackgroundThe aim of the current investigation is to test whether determination of copeptin, an indirect marker for arginin-vasopressin, adds diagnostic information to cardiac troponin in early evaluation of patients with suspected myocardial infarction.MethodsBetween January 2007 and July 2008, patients with suspected acute coronary syndrome were consecutively enrolled in this multicenter study. Copeptin, troponin T (TnT), myoglobin, and creatine kinase-myocardial band were determined at admission and after 3 and 6 h.ResultsOf 1,…
Sensitive Troponin I Assay in Early Diagnosis of Acute Myocardial Infarction
BACKGROUND Cardiac troponin testing is central to the diagnosis of acute myocardial infarction. We evaluated a sensitive troponin I assay for the early diagnosis and risk stratification of myocardial infarction. METHODS In a multicenter study, we determined levels of troponin I as assessed by a sensitive assay, troponin T, and traditional myocardial necrosis markers in 1818 consecutive patients with suspected acute myocardial infarction, on admission and 3 hours and 6 hours after admission. RESULTS For samples obtained on admission, the diagnostic accuracy was highest with the sensitive troponin I assay (area under the receiver-operating-characteristic curve [AUC], 0.96), as compared with t…
Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins.
Recruitment and activation of polymorphonuclear neutrophils (PMNs) reflects a primary immunological response to invading pathogens and has also emerged as a hallmark of vascular inflammation. One of the principal enzymes released upon PMN activation is myeloperoxidase (MPO), a heme protein that not only generates cytotoxic oxidants but also impacts deleteriously on nitric oxide-dependent signaling cascades within the vasculature. Because MPO also associates with the membrane of PMN, we evaluated whether MPO could also function as an autocrine modulator of PMN activation. The extent of PMN membrane-associated MPO was elevated in patients with acute inflammatory vascular disease compared with…
Six-Month Outcomes of the Tri-Repair Study Assessing the Cardioband Tricuspid Valve Reconstruction System for Patients with Severe Tricuspid Regurgitation
Background: Severe tricuspid regurgitation (TR) is associated with high morbidity and mortality rates with limited treatment options. We report the six-month safety and performance of the Cardioband™ Tricuspid Valve Reconstruction System in the treatment of severe functional TR in 30 patients enrolled in the TRI-REPAIR study. Methods: Between October 2016 and July 2017, 30 patients were enrolled in this single-arm, multicenter, prospective trial. Patients were diagnosed with severe, symptomatic TR in the absence of untreated left-heart disease and deemed inoperable because of unacceptable risk for open-heart surgery by the local heart team. Clinical, functional, and echocardiographic data w…
Impact of Residual Mitral Regurgitation on Survival After Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.
OBJECTIVES The aim of this study was to assess the impact of residual mitral regurgitation (resMR) on mortality with respect to left ventricular dilatation (LV-Dil) or right ventricular dysfunction (RV-Dys) in patients with secondary mitral regurgitation (SMR) who underwent mitral valve transcatheter edge-to-edge repair (TEER). BACKGROUND The presence of LV-Dil and RV-Dys correlates with advanced stages of heart failure in SMR patients, which may impact the outcome after TEER. METHODS SMR patients in a European multicenter registry were evaluated. Investigated outcomes were 2-year all-cause mortality and improvement in New York Heart Association functional class with respect to MR reduction…
Identification of acute myocardial infarction in elderly patients using optimized highly sensitive troponin I thresholds
Purpose: Established diagnostic thresholds for high-sensitivity cardiac troponins (hs-cTn) might not apply for elderly patients as they are elevated irrespective of the presence of an acute myocardial infarction (AMI). Aim of the present study was to investigate hs-cTnI in elderly patients with suspected AMI and to calculate optimized diagnostic cutoffs. Material and methods: Data from a prospective multi-centre study and from a second independent prospective single-centre cohort study were analysed. A number of 2903 patients were eligible for further analysis. Patients > 70 years were classified as elderly. hs-cTnI was measured upon admission. Results: Around 34.7% of 2903 patients were…
Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia
Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 × 10(-41)) and in 1690 AA subjects (rs505102; P = 1.05 × 10(-8)). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare M…
Mechanisms of Increased Vascular Superoxide Production in an Experimental Model of Idiopathic Dilated Cardiomyopathy
Objective— In the present study, we sought to identify mechanisms underlying increased oxidative stress in vascular tissue in an experimental animal model of chronic congestive heart failure (CHF). Methods and Results— Superoxide and nitric oxide (NO) was measured in vessels from cardiomyopathic hamsters (CHF hamsters) and golden Syrian hamsters. We also determined expression of endothelial nitric oxide synthase (NOSIII), the soluble guanylyl cyclase, the cGMP-dependent kinase, and the NADPH oxidase. To analyze the contribution of the renin-angiotensin system to oxidative stress, CHF hamsters were treated with the angiotensin-converting enzyme inhibitor captopril for 200 days (120 mg · kg …
Gender-specific diagnostic performance of a new high-sensitivity cardiac troponin I assay for detection of acute myocardial infarction.
The determination of cardiac troponin is essential for diagnosing myocardial infarction. A troponin I assay has recently been developed that provides the highest analytical sensitivity to date.The analysis included 1560 patients with chest pain, of whom 1098 were diagnosed with non-coronary chest pain, 189 with unstable angina pectoris and 273 with non-ST-segment elevation myocardial infarction. The troponin I concentration was determined on admission (0 hours) and 3 hours later. The diagnostic algorithm incorporated troponin I elevation above the gender-specific 99th percentile as well as predefined relative or absolute 3-hour changes in the troponin I concentration (delta).The diagnostic …
Urinary neutrophil gelatinase-associated lipocalin and cystatin C compared to the estimated glomerular filtration rate to predict risk in patients with suspected acute myocardial infarction.
Abstract Introduction Impaired renal function, reflected by estimated glomerular filtration rate (eGFR) or cystatin C, is a strong risk predictor in the presence of acute myocardial infarction (AMI). Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is an early marker of acute kidney injury. uNGAL might also be a good predictor of outcome in patients with cardiovascular disease. Aim of the present study was to evaluate the prognostic value of uNGAL compared to eGFR and cystatin C in patients with suspected AMI. Methods 1818 patients were enrolled with suspected AMI. Follow-up information on the combined endpoint of death or non-fatal myocardial infarction was obtained 6months after…
First Evidence for a Crosstalk Between Mitochondrial and NADPH Oxidase-Derived Reactive Oxygen Species in Nitroglycerin-Triggered Vascular Dysfunction
Chronic nitroglycerin treatment results in development of nitrate tolerance associated with endothelial dysfunction (ED). We sought to clarify how mitochondria- and NADPH oxidase (Nox)-derived reactive oxygen species (ROS) contribute to nitrate tolerance and nitroglycerin-induced ED. Nitrate tolerance was induced by nitroglycerin infusion in male Wistar rats (100 microg/h/4 day) and in C57/Bl6, p47(phox/) and gp91(phox/) mice (50 microg/h/4 day). Protein and mRNA expression of Nox subunits were unaltered by chronic nitroglycerin treatment. Oxidative stress was determined in vascular rings and mitochondrial fractions of nitroglycerin-treated animals by L-012 enhanced chemiluminescence, revea…