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Aim: Presepsin is a sensitive biomarker for the diagnosis and estimation of prognosis in septic patients. The prognostic role of presepsin in patients undergoing transcatheter aortic valve implantation (TAVI) has never been investigated. Patients, materials & methods: In 343 patients, presepsin and N-terminal pro-B-type natriuretic peptide were measured before TAVI. One-year all-cause mortality was used as outcome measure. Results: Patients with high presepsin levels were more likely to succumb than patients with low presepsin values (16.9% vs 12.3%; p = 0.015). Elevated presepsin remained a significant predictor of 1-year all-cause mortality (odds ratio: 2.2 [95% CI: 1.12–4.29]; p = 0.022) after adjustment. N-terminal pro-B-type natriuretic peptide did not predict 1-year all-cause mortality. Conclusion: Elevated baseline presepsin levels are an independent predictor of 1-year mortality in TAVI patients.

Background Chronic right heart failure is the major determinant of outcome in chronic thromboembolic pulmonary hypertension (CTEPH). Thus, its early detection is crucial for optimal patient management. Hemodynamic assessment with invasive right heart catheterization and the measurement of natriuretic peptides at rest are established diagnostic tools in this context. An elevated right atrial pressure (RAP) is a sensitive parameter of right right heart failure. Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a natriuretic peptide that reflects right atrial stress levels. There is a growing recognition of exercise diagnostics in the assessment of right heart failure, particularly in patients with normal or borderline findings at rest. There are no data on the dynamics of MR-proANP in correlation to RAP during physical exercise. Purpose The present study was designed to investigate the dynamics of RAP and MR-proANP during physical exercise in patients with CTEPH and to determine whether these parameters might serve as a tool to measure exercise-dependent atrial stress as an indicator of right heart failure. Methods This observational cohort study included 100 CTEPH patients who underwent right heart catheterization during physical exercise (eRHC). Blood samples for MR-proANP measurement were taken prior, during, and after eRHC. MR-proANP levels were correlated to RAP levels at rest, at peak exercise (eRAP), and during recovery. RAP at rest ≤7 mmHg was defined as normal and eRAP >15 mmHg as suggestive of right heart failure. Results During eRHC mean RAP increased from 6±4 mmHg to 16±7 mmHg (p15 mmHg. Physical exercise unmasked RH failure in 39% of patients with normal RAP at rest; they were also characterized by a more distinct increase in MR-proANP levels (p=0.005) and higher peak (p Conclusions RAP and MR-proANP dynamics unmask manifest and latent right heart failure in CTEPH patients, which may be useful in estimating prognosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): SFB 1213 area CP-01 projectWilliam G. Kerckhoff-FoundationKerckhoff Heart Research Institute (KHFI)German Center for Cardiovascular Research (DZHK)

Quantifizierung der links- und rechtsventrikulären Funktion Strain Imaging erweitert die klassische Volumetrie der MRT um einen sehr subtilen globalen und regionalen Funktionsparameter. Strain detektiert sehr frühe Funktionseinbußen beider Ventrikel, die visuell noch nicht erkennbar sind. Insbesondere der longitudinale Strain ist bei ischämischen und nichtischämischen Erkrankungen frühzeitig reduziert. Strain hat über die EF hinaus zusätzliche prognostische Bedeutung. Gewebecharakterisierung T1- und T2-Mapping erweitern die klassische Gewebecharakterisierung mit Late Gadolinium Enhancement (LGE) um sehr subtile quantitative Parameter, die diffuse Fibrose (T1) und Ödem (T1 und T2) widerspiegeln. Ischämiediagnostik Die Perfusions-MRT unter Vasodilatatorstress ist das genaueste Verfahren zur Ischämiediagnostik. Die MR-INFORM-Studie zeigt, dass mithilfe der Stress-MRT fast die Hälfte der Katheteruntersuchungen in einem Kollektiv mit hoher Prätestwahrscheinlichkeit vermieden werden kann. Dabei ist die Stress-MRT der FFR-basierten Strategie nicht unterlegen und genauso sicher.

Background Cardiac amyloidosis (CA) is an infiltrative disease characterised by accumulation of amyloid deposits in the extracellular space of the myocardium—comprising transthyretin (ATTR) and light chain (AL) amyloidosis as the most frequent subtypes. Histopathological proof of amyloid deposits by endomyocardial biopsy (EMB) is the gold standard for diagnosis of CA. Cardiovascular magnetic resonance (CMR) allows non-invasive workup of suspected CA. We conducted a multi-centre study to assess the diagnostic value of CMR in comparison to EMB for the diagnosis of CA. Methods We studied N = 160 patients characterised by symptoms of heart failure and presence of left ventricular (LV) hypertrophy of unknown origin who presented to specialised cardiomyopathy centres in Germany and underwent further diagnostic workup by both CMR and EMB. If CA was diagnosed, additional subtyping based on EMB specimens and monoclonal protein studies in serum was performed. The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging as well as native and post-contrast T1-mapping (in a subgroup)—allowing to measure extracellular volume fraction (ECV) of the myocardium. Results An EMB-based diagnosis of CA was made in N = 120 patients (CA group) whereas N = 40 patients demonstrated other diagnoses (CONTROL group). In the CA group, N = 114 (95%) patients showed a characteristic pattern of LGE indicative of CA. In the CONTROL group, only 1/40 (2%) patient showed a “false-positive” LGE pattern suggestive of CA. In the CA group, there was no patient with elevated T1-/ECV-values without a characteristic pattern of LGE indicative of CA. LGE-CMR showed a sensitivity of 95% and a specificity of 98% for the diagnosis of CA. The combination of a characteristic LGE pattern indicating CA with unremarkable monoclonal protein studies resulted in the diagnosis of ATTR-CA (confirmed by EMB) with a specificity of 98% [95%-confidence interval (CI) 92–100%] and a positive predictive value (PPV) of 99% (95%-CI 92–100%), respectively. The EMB-associated risk of complications was 3.13% in this study—without any detrimental or persistent complications. Conclusion Non-invasive CMR shows an excellent diagnostic accuracy and yield regarding CA. When combined with monoclonal protein studies, CMR can differentiate ATTR from AL with high accuracy and predictive value. However, invasive EMB remains a safe invasive gold-standard and allows to differentiate CA from other cardiomyopathies that can also cause LV hypertrophy.

BACKGROUND Activation of inflammatory pathways during acute myocardial infarction contributes to infarct size and left ventricular (LV) remodeling. The present prospective randomized clinical trial was designed to test the efficacy and safety of broad-spectrum anti-inflammatory therapy with a mammalian target of rapamycin (mTOR) inhibitor to reduce infarct size. DESIGN Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS, clinicaltrials.gov NCT01529554) is a phase II randomized, double-blind, multi-center, placebo-controlled trial on the effects of a 5-day course of oral everolimus on infarct size, LV remodeling, and inflammation in patients with acute ST-elevation myocardial infarction (STEMI). Within 5 days of successful primary percutaneous coronary intervention (pPCI), patients are randomly assigned to everolimus (first 3 days: 7.5 mg qd; days 4 and 5: 5.0 mg qd) or placebo, respectively. The primary efficacy outcome is the change from baseline (defined as 12 h to 5 days after pPCI) to 30-day follow-up in myocardial infarct size as measured by cardiac magnetic resonance imaging (CMRI). Secondary endpoints comprise corresponding changes in cardiac and inflammatory biomarkers as well as microvascular obstruction and LV volumes assessed by CMRI. Clinical events, laboratory parameters, and blood cell counts are reported as safety endpoints at 30 days. CONCLUSION The CLEVER-ACS trial tests the hypothesis whether mTOR inhibition using everolimus at the time of an acute STEMI affects LV infarct size following successful pPCI.

The concept of developmental origin of health and disease has ignited a search for mechanisms and health factors influencing normal intrauterine development. Sleep is a basic health factor with substantial individual variation, but its implication for early prenatal development remains unclear. During the embryonic period, the yolk sac is involved in embryonic nutrition, growth, hematopoiesis, and likely in fetal programming. Maternal body measures seem to influence its size in human female embryos. In this prospective, longitudinal observational study of 190 healthy women recruited before natural conception, we assessed the effect of prepregnant sleep duration (actigraphy) on the fetal crown-rump-length (CRL) and yolk sac size (ultrasound). All women gave birth to a live child. The prepregnancy daily sleep duration had an effect on the male yolk sac and CRL at the earliest measurement only (7 weeks). I.e., the yolk sac diameter decreased with increasing sleep duration (0.22 mm·h−1d−1, 95%CI [0.35–0.09], P 0.01), and CRL increased (0.92 mm·h−1d−1, 95%CI [1.77–0.08], P = 0.03). Since there was no association at the second measurement (10 weeks), and in the group of female fetuses at any measure point, we suggest a sex- and time-dependent embryonic adaptation to sleep generated differences in the intrauterine environment in normal pregnancies.

Background In chronic thromboembolic pulmonary hypertension, right heart failure determines outcome. Balloon pulmonary angioplasty therapy allows right heart recovery, which can be monitored by cardiac magnetic resonance imaging. This study evaluates whether cardiac biomarkers (NT-proBNP, MR-proANP, sST2, and PAPP-A) are associated with cardiac magnetic resonance imaging findings prior to and after balloon pulmonary angioplasty therapy. Methods This observational cohort study enrolled 22 chronic thromboembolic pulmonary hypertension patients who underwent balloon pulmonary angioplasty therapy and completed a six-month follow-up including cardiac magnetic resonance imaging. Biomarker levels were compared with findings for right heart morphology and function derived from cardiac magnetic resonance imaging. Results Pulmonary hemodynamics improved after balloon pulmonary angioplasty therapy [pulmonary vascular resistance: 7.7 (6.0–9.0) vs. 4.7 (3.5–5.5) wood units, p

The main aim of this study was to assess the prognostic utility of TAPSE/PASP as an echocardiographic parameter of maladaptive RV remodeling in cardiomyopathy patients using cardiac magnetic resonance (CMR) imaging. Furthermore, we sought to compare TAPSE/PASP to TAPSE. The association of the echocardiographic parameters TAPSE/PASP and TAPSE with CMR parameters of RV and LV remodeling was evaluated in 111 patients with ischemic and non-ischemic cardiomyopathy and cut-off values for maladaptive RV remodeling were defined. In a second step, the prognostic value of TAPSE/PASP and its cut-off value were analyzed regarding mortality in a validation cohort consisting of 221 patients with ischemic and non-ischemic cardiomyopathy. A low TAPSE/PASP (

The aim of this study was to evaluate the cartilage intermediate layer protein 1 (CILP1) as a biomarker of right ventricular dysfunction in patients with ischemic cardiomyopathy (ICM). CILP1 plasma concentrations were measured in 98 patients with ICM and 30 controls without any cardiac abnormalities. All participants underwent cardiac magnetic resonance imaging. Median CILP1 concentrations were higher in ICM than in controls. In the tertile analysis, low right ventricular ejection fraction (RVEF) and high right ventricular end-systolic volume index and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with higher CILP1 levels in ICM. However, there were no associations between CILP1 concentrations and left ventricular (LV) parameters in this group. In receiver-operating characteristic (ROC) analysis CILP1 was a good predictor of RVEF 40% with an optimal cut-off value of 3545 pg/ml in ICM, whereas it was not predictive of LV ejection fraction (LVEF) 40% (area under the curve [AUC] = 0.57) There was no significant difference between the ROC curves of CILP1 (AUC = 0.72) and NT-proBNP (AUC = 0.77) for RVEF 40% (

Left ventricular (LV) longitudinal, circumferential, and radial motion can be measured using feature tracking of cardiac magnetic resonance (CMR) images. The aim of our study was to detect differences in LV mechanics between patients with dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) who were matched using a propensity score-based model. Between April 2017 and October 2019, 1224 patients were included in our CMR registry, among them 141 with ICM and 77 with DCM. Propensity score matching was used to pair patients based on their indexed end-diastolic volume (EDVi), ejection fraction (EF), and septal T1 relaxation time (psmatch2 module L Feature tracking provided six parameters for global longitudinal, circumferential, and radial strain with corresponding strain rates in each group. Strain parameters were compared between matched pairs of ICM and DCM patients using paired t tests. Propensity score matching yielded 72 patients in each group (DCM mean age 58.6 ± 11.6 years, 15 females; ICM mean age 62.6 ± 13.2 years, 11 females, p = 0.084 and 0.44 respectively; LV-EF 32.2 ± 13.5% vs. 33.8 ± 12.1%, p = 0.356; EDVi 127.2 ± 30.7 ml/m2 vs. 121.1 ± 41.8 ml/m2, p = 0.251; native T1 values 1165 ± 58 ms vs. 1167 ± 70 ms, p = 0.862). There was no difference in global longitudinal strain between DCM and ICM patients (− 10.9 ± 5.5% vs. − 11.2 ± 4.7%, p = 0.72), whereas in DCM patients there was a significant reduction in global circumferential strain (− 10.0 ± 4.5% vs. − 12.2 ± 4.7%, p = 0.002) and radial strain (17.1 ± 8.51 vs. 21.2 ± 9.7%, p = 0.039). Our data suggest that ICM and DCM patients have inherently different myocardial mechanics, even if phenotypes are similar. Our data show that GCS is significantly more impaired in DCM patients. This feature may help in more thoroughly characterizing cardiomyopathy patients.

OBJECTIVES: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. METHODS: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC)

Cardiac magnetic resonance is the only imaging modality, that allows for characterising myocardial tissue with respect to fibrosis and edema. It has therefore become gold standard in diagnosing myocardial inflammation by combining scar, fibrosis and edema imaging. Recent developements in T1- and T2 mapping have improved diagnostic accuracy and prognostic information.QUANTIFIZIERUNG DER LINKS- UND RECHTSVENTRIKULäREN FUNKTION: Strain Imaging erweitert die klassische Volumetrie der MRT um einen sehr subtilen globalen und regionalen Funktionsparameter. Strain detektiert sehr frühe Funktionseinbußen beider Ventrikel, die visuell noch nicht erkennbar sind. Insbesondere der longitudinale Strain ist bei ischämischen und nichtischämischen Erkrankungen frühzeitig reduziert. Strain hat über die EF hinaus zusätzliche prognostische Bedeutung. GEWEBECHARAKTERISIERUNG: T1- und T2-Mapping erweitern die klassische Gewebecharakterisierung mit Late Gadolinium Enhancement (LGE) um sehr subtile quantitative Parameter, die diffuse Fibrose (T1) und Ödem (T1 und T2) widerspiegeln. · Die T1-Relaxationszeit misst im Gegensatz zum LGE auch diffuse Gewebeveränderungen.. · Die T1-Zeit ist erhöht bei akuten inflammatorischen Veränderungen sowie chronischer Fibrose.. · Die T1-Relaxationszeit ist erniedrigt bei Hämochromatose und Morbus Fabry.. · Die T2-Relaxationszeit ist erhöht bei akuten inflammatorischen Veränderungen.. · Die T1-Relaxationszeit beinhaltet prognostische Information, die additiv zur EF ist.. ISCHäMIEDIAGNOSTIK: Die Perfusions-MRT unter Vasodilatatorstress ist das genaueste Verfahren zur Ischämiediagnostik. Die MR-INFORM-Studie zeigt, dass mithilfe der Stress-MRT fast die Hälfte der Katheteruntersuchungen in einem Kollektiv mit hoher Prätestwahrscheinlichkeit vermieden werden kann. Dabei ist die Stress-MRT der FFR-basierten Strategie nicht unterlegen und genauso sicher.

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Primary coronary slow-flow phenomenon (CSFP) is defined as delayed opacification of contrast media in at least 1 coronary vessel in the absence of obstructive epicardial coronary artery disease (CAD) during coronary angiography. Epicardial fat tissue (EFT) surrounding coronary vessels provides paracrine effects. Released cytokines diffusing in the vessel wall may induce local inflammatory reactions that potentially result in endothelial dysfunction. The latter is thought to be the underlying cause of primary CSFP. However, to date, there are no data describing an association between EFT and CSFP. Therefore, the aim of the present study was to compare EFT thickness, clinical parameters, and outcomes in patients with and without CSFP.Coronary angiograms with primary CSFP obtained during a 10-year period were included in the analysis. EFT was measured in the 2-dimensional echocardiographic records. Clinical and diagnostic data were compared with non-CSFP patients who were matched for age, sex, and body mass index. Long-term follow-up was conducted by telephone interview.A total of 48 CSFP patients (90% male; mean age, 64 ± 11.4 years) were identified, resulting in a prevalence of 0.13%. CSFP was observed in 87.5% in the left anterior descending artery, 50% in the right coronary artery, and 20.8% in the circumflex artery. Almost half of all patients showed CSFP in1 vessel. There were no differences in baseline characteristics between CSFP patients and matched controls except for smoking history (31% vs 13%; P=.03). Median EFT thickness was significantly different between patients with and without CSFP (4.9 mm [interquartile range, 4.0-6.1 mm] vs 3.9 mm [interquartile range, 3.1-4.9 mm], respectively; P.01). No differences in outcomes were observed.EFT is thicker in CSFP patients than in matched controls, but this appears to have no impact on long-term outcomes. Further studies are needed to elucidate the role of EFT in CSFP.

Background Sleep and physical activity changes are common in pregnancy, but longitudinal data starting before conception are scarce. Our aim was to determine the changes of the daily total sleep time (TST) and physical activity duration (PAD) from before conception to end of pregnancies in respect of pregestational maternal factors. Methods This longitudinal observational study formed part of the CONIMPREG research project and recruited healthy women planning to become pregnant. Sleep and physical activity were recorded around-the-clock for ≥4 days via actigraphy before conception and during each trimester of pregnancy. Data were adjusted according to pregestational maternal body composition, parity and age. Results Among 123 women with eligible data, the unadjusted mean (95% confidence interval) TST increased from 415.3 min (405.5–425.2 min) before conception to 458.0 min (445.4–470.6 min) in the 1st trimester, remaining high through the 2nd and 3rd trimesters. Variation was substantial before conception (±2SD range: 307–523 min). The unadjusted mean PAD before conception was 363.7 min (±2SD range: 120–608 min), decreasing sharply to 262.1 min in the first trimester and more gradually thereafter. Vigorous and moderate activity decreased more than light activity. TST and PAD were significantly associated with age, parity, and pregestational body fat percentage; lean body mass was negatively correlated with TST. Results were generally unaffected by seasonal variations. Conclusion Marked variations were found in pregestational TST and PAD. Healthy women slept ≥30 min longer during pregnancy, while PAD decreased by ≥ 90 min in early pregnancy and continued to decrease thereafter.