Julia Mascherbauer

Coronary Neutrophil Extracellular Trap Burden and Deoxyribonuclease Activity in ST-Elevation Acute Coronary Syndrome Are Predictors of ST-Segment Resolution and Infarct Size

RATIONALE Mechanisms of coronary occlusion in ST-elevation acute coronary syndrome are poorly understood. We have previously reported that neutrophil (polymorphonuclear cells [PMNs]) accumulation in culprit lesion site (CLS) thrombus is a predictor of cardiovascular outcomes. OBJECTIVE The goal of this study was to characterize PMN activation at the CLS. We examined the relationships between CLS neutrophil extracellular traps (NETs), bacterial components as triggers of NETosis, activity of endogenous deoxyribonuclease, ST-segment resolution, and infarct size. METHODS AND RESULTS We analyzed coronary thrombectomies from 111 patients with ST-elevation acute coronary syndrome undergoing primary percutaneous coronary intervention. Thrombi were characterized by immunostaining, flow cytometry, bacterial profiling, and immunometric and enzymatic assays. Compared with femoral PMNs, CLS PMNs were highly activated and formed aggregates with platelets. Nucleosomes, double-stranded DNA, neutrophil elastase, myeloperoxidase, and myeloid-related protein 8/14 were increased in CLS plasma, and NETs contributed to the scaffolds of particulate coronary thrombi. Copy numbers of Streptococcus species correlated positively with dsDNA. Thrombus NET burden correlated positively with infarct size and negatively with ST-segment resolution, whereas CLS deoxyribonuclease activity correlated negatively with infarct size and positively with ST-segment resolution. Recombinant deoxyribonuclease accelerated the lysis of coronary thrombi ex vivo. CONCLUSIONS PMNs are highly activated in ST-elevation acute coronary syndrome and undergo NETosis at the CLS. Coronary NET burden and deoxyribonuclease activity are predictors of ST-segment resolution and myocardial infarct size.

Cardiac Magnetic Resonance Postcontrast T1 Time Is Associated With Outcome in Patients With Heart Failure and Preserved Ejection Fraction

Background—The underlying pathophysiology of heart failure with preserved ejection fraction (HFPEF) is incompletely understood, but myocardial extracellular matrix accumulation is thought to play a major role. Our aims were to estimate myocardial extracellular matrix using cardiac magnetic resonance T1 mapping and to assess the relationship between pathobiology/pathophysiology and prognosis. Methods and Results—Patients with suspected HFPEF (n=100) were enrolled in this prospective, observational study. Confirmatory diagnostic tests, cardiac magnetic resonance imaging including T1 mapping, and invasive hemodynamic assessments were performed at baseline. Sixty-one patients with confirmed HFPEF entered a longitudinal outcome-monitoring phase (mean, 22.9±5.0 months), during which 16 had a cardiac event. Cardiac magnetic resonance T1 time (hazard ratio, 0.99; 95% confidence interval, 0.98–0.99; P=0.046), left atrial area (hazard ratio, 1.08; 95% confidence interval, 1.03–1.13; P<0.01), and pulmonary vascular resistance (hazard ratio, 1.01; 95% confidence interval, 1.00–1.01; P=0.03) were significantly associated with cardiac events. Patients with T1 times below the median (<388.3 ms) were at greater risk of cardiac events than the rest of the group (P<0.01). Extracellular matrix of left ventricular biopsies (n=9), quantified by TissueFAXS technology correlated with T1 time (R=0.98; P<0.01). T1 time also correlated with right ventricular–pulmonary arterial coupling (pulmonary vascular resistance: R=−0.36; P<0.01; right ventricular ejection fraction: R=0.28; P=0.01). Conclusions—In the present preliminary study, cardiac magnetic resonance postcontrast T1 time is associated with prognosis in HFPEF, suggesting postcontrast T1 as possible biomarker for HFPEF.

Gender differences in clinical presentation and surgical outcome of aortic stenosis

Background Little is known about the gender differences of patients undergoing aortic valve replacement (AVR) for isolated severe aortic stenosis. Methods and Results 408 consecutive patients (215 women and 193 men; p=0.9) were analysed. At presentation, women were older (73.7±9.3 years vs men 66.5±11.5 years; p<0.001), more symptomatic (New York Heart Association (NYHA) class: women 2.3±0.7 vs men 2.0±0.65; p<0.001), and presented with smaller valve areas (women 0.6±0.2 cm2 vs men 0.7±0.2 cm2; p<0.001) and higher mean pressure gradients (women 67.3±19.2 mm Hg vs men 62.2±20.0 mm Hg, p=0.001). Despite older age and more advanced disease in women, operative mortality did not differ. Survival after AVR by Kaplan–Meier analysis tended to be even better in women (92.8%, 89.8%, 81.4% vs men 89.1%, 86.6%, 76.3% at 1, 2 and 5 years, p=0.31). After division into age quintiles, the outcome of women was significantly better in patients older than 79 years (p=0.005). After adjustment for clinical characteristics, gender did not predict operative mortality and late outcome. Despite physical improvement in both groups after surgery, women remained more symptomatic (NYHA class: women 1.6±0.7 vs men 1.3±0.4; p=0.001). Conclusion Although women referred to AVR are older and more symptomatic, operative and long-term mortality are not increased. In the oldest age group of 79 years and older, women even have a better outcome, presumably due to a longer mean life expectancy.

T1 Mapping by CMR Imaging: From Histological Validation to Clinical Implication

OBJECTIVES The purpose of this study was to prospectively investigate the diagnostic and prognostic impact of cardiac magnetic resonance (CMR) T1 mapping and validate it against left ventricular biopsies. BACKGROUND Extracellular volume (ECV) expansion is a key feature of heart failure. CMR T1 mapping has been developed as a noninvasive technique to estimate ECV; however, the diagnostic and prognostic impacts of this technique have not been well established. METHODS A total of 473 consecutive patients referred for CMR (49.5% female, age 57.8 ± 17.1 years) without hypertrophic cardiomyopathy, cardiac amyloidosis, or Anderson-Fabry disease were studied. T1 mapping with the modified Look-Locker inversion recovery (MOLLI) sequence was used for ECV calculation (CMR-ECV). For methodological validation, 36 patients also underwent left ventricular biopsy, and ECV was quantified by TissueFAXS analysis (TissueFAXS-ECV). To assess the prognostic value of CMR-ECV, its association with hospitalization for cardiovascular reasons or cardiac death was tested in a multivariable Cox regression model. RESULTS TissueFAXS-ECV was 26.3 ± 7.2% and was significantly correlated with CMR-ECV (r = 0.493, p = 0.002). Patients were followed up for 13.3 ± 9.0 months and divided into CMR-ECV tertiles for Kaplan-Meier analysis (tertiles were ≤ 25.7%, 25.8% to 28.5%, and ≥ 28.6%). Significantly higher event rates were observed in patients with higher CMR-ECV (log-rank p = 0.013). By multivariable Cox regression analysis, CMR-ECV was independently associated with outcome among imaging variables (p = 0.004) but not after adjustment for clinical parameters. CONCLUSIONS CMR T1 mapping allows accurate noninvasive quantification of ECV and is independently associated with event-free survival among imaging parameters. Its prognostic value on top of established clinical risk factors warrants further investigation in long-term studies.

Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI)

Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR). Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV). These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water). Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment. There is a multitude of technical approaches and potential applications. This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.

Impact of tricuspid regurgitation on survival in patients with chronic heart failure: unexpected findings of a long-term observational study

AIMS Tricuspid regurgitation (TR) is common in patients with chronic heart failure (CHF) but its prognostic impact is unclear. METHODS AND RESULTS A total of 576 consecutive patients with CHF were prospectively included. The impact of moderate and severe (significant) TR on the combined endpoint death/heart transplantation/left ventricular-assist device implantation was assessed. Patients were followed for 5.8 ± 4.2 (maximum 14.4) years. Kaplan-Meier analysis showed a worse outcome of patients with significant TR (P < 0.0001). By multivariable analysis, amino terminal pro B-type natriuretic peptide (NT-proBNP) (P = 0.0028), systolic left ventricular function (LVF) (P = 0.0014), serum sodium, NYHA functional class, systolic blood pressure, right atrial size (all P = 0.0001), but not TR were significantly related with the outcome. However, as soon as the strong interaction between TR and LVF was included in the model, significant TR determined outcome as well (P = 0.0059). Therefore, in a second analysis patients were stratified for LVF. In patients with mildly or moderately impaired LVF, TR was significantly related with the outcome (HR: 1.368, CI: 1.070-1.748, P = 0.0125), whereas in patients with severely depressed LVF it was not (P = 0.1401). As a proof of concept, we additionally stratified patients according to serum NT-proBNP concentrations. In patients with NT-proBNP concentrations below the median (≤ 280 fmol/mL), TR was related with the outcome (HR: 2.512, CI: 1.127-5.597, P = 0.0242) but it was not in patients with NT-proBNP concentrations above the median (P = 0.3935). CONCLUSION The prognostic impact of TR depends on the severity of CHF. While TR was significantly related with excess mortality in mild to moderate CHF, it provided no additive value in advanced disease when compared with established risk factors.

The right heart in heart failure with preserved ejection fraction: insights from cardiac magnetic resonance imaging and invasive haemodynamics.

Recent data indicate that right ventricular systolic dysfunction (RVSD) by cardiac magnetic resonance imaging (CMR) is a strong predictor of outcome in heart failure. However, the prognostic significance of RVSD by CMR in heart failure with preserved ejection fraction (HFpEF) is unknown.

Moderate patient-prosthesis mismatch after valve replacement for severe aortic stenosis has no impact on short-term and long-term mortality

Background: The importance of moderate patient-prosthesis mismatch (PPM) for the prognosis of patients who undergo aortic valve replacement is unclear. Methods: The presence of PPM was assessed in 361 consecutive patients undergoing valve replacement for isolated severe aortic stenosis and related to perioperative and postoperative mortality. Indexed effective orifice areas (EOAi) were estimated for each type and size of prosthesis. Results: Using the previously proposed cut-off of EOAi ⩽0.8 cm2/m2, PPM was present in 54% of patients. Patients were followed for 4.1 (2.0) years. Survival tended to be slightly, but insignificantly, worse in the group with PPM (1-year, 3-year and 5-year survival 89%, 86% and 76% vs 92%, 88% and 82%; p = 0.21). However, patients with PPM were also older (p<0.0001), more often female (p<0.0001), more symptomatic (p = 0.001), more often had coronary artery disease (p = 0.04), triple vessel disease (p = 0.03) and hypertension (p = 0.01) and presented with a higher EuroSCORE (p<0.0001). By multivariate analysis only EuroSCORE and diabetes but not PPM were independent predictors of survival. Conclusions: Moderate PPM is a frequent finding after aortic valve replacement. In our patient population it had no impact on short-term and long-term survival. It may therefore not be justified to recommend complex surgical interventions to avoid moderate PPM in patients undergoing aortic valve replacement for isolated severe aortic stenosis.

Prognostic value of serial B-type natriuretic peptide measurement in asymptomatic organic mitral regurgitation

Optimal timing of surgery is crucial in mitral regurgitation (MR) to avoid excess mortality and morbidity. The role of brain‐type natriuretic peptide (BNP) in this setting remains controversial. We evaluated the value of serial BNP measurements for early prediction of deterioration in asymptomatic MR.

The forgotten valve: lessons to be learned in tricuspid regurgitation

This editorial refers to ‘Geometric changes after tricuspid annuloplasty and predictors of residual tricuspid regurgitation: a real-time three-dimensional echocardiography study’, by S.-Y. Min et al. doi:10.1093/eurheartj/ehq227 Only limited information is currently available about the prognostic significance of tricuspid regurgitation (TR). The few existing studies, however, suggest a strong impact of TR on clinical outcome. Significant TR is associated with poor prognosis in patients with mitral stenosis after percutaneous balloon valvuloplasty1 and with a reduction in exercise capacity after mitral valve surgery.2 A significant increase in mortality among patients with moderate and severe TR has been reported, which was independent of left ventricular ejection fraction or pulmonary artery pressure.3 In 60 patients with flail tricuspid leaflet due to trauma, significant increases in atrial fibrillation, heart failure, and death were observed.4 TR was also an independent predictor of increased mortality in 1400 patients with left ventricular systolic dysfunction.5 TR is only rarely caused by primary abnormalities of the tricuspid leaflets. In most instances it is ‘functional’ in nature and is the consequence of geometric alterations caused by right ventricular dilatation,6,7 distortion of the subvalvular apparatus, tricuspid annular dilatation, or a combination … *Corresponding athor. Tel: +43 1 40 400 4614, Fax: +43 1 40400 4216, E-mail: gerald.maurer{at}meduniwien.ac.at