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SummaryThe prevalence and significance of cardiac amyloidosis have been considerably underestimated in the past; however, the number of patients diagnosed with cardiac amyloidosis has increased significantly recently due to growing awareness of the disease, improved diagnostic capabilities and demographic trends. Specific therapies that improve patient prognosis have become available for certain types of cardiac amyloidosis. Thus, the earliest possible referral of patients with suspicion of cardiac amyloidosis to an experienced center is crucial to ensure rapid diagnosis, early initiation of treatment, and structured patient care. This requires intensive collaboration across several disciplines, and between resident physicians and specialized centers. The aim of this consensus statement is to provide guidance for the rapid and efficient diagnosis and treatment of light-chain amyloidosis and transthyretin amyloidosis, which are the most common forms of cardiac amyloidosis.

Background. Transcatheter edge-to-edge mitral valve repair (TMVR) is increasingly performed. However, its efficacy in comparison with surgical MV treatment (SMV) is unknown. Methods. Consecutive patients with severe mitral regurgitation (MR) undergoing TMVR (68% functional, 32% degenerative) or SMV (9% functional, 91% degenerative) were enrolled. To account for differences in baseline characteristics, propensity score matching was performed, including age, EuroSCORE-II, left ventricular ejection fraction, and NT-proBNP. A composite of heart failure (HF) hospitalization/death served as primary endpoint. Kaplan-Meier curves and Cox-regression analyses were used to investigate associations between baseline, imaging, and procedural parameters and outcome. Results. Between July 2017 and April 2020, 245 patients were enrolled, of whom 102 patients could be adequately matched (73 y/o, 61% females, EuroSCORE-II: 5.7%, p > 0.05 for all). Despite matching, TMVR patients had more co-morbidities at baseline (higher rates of prior myocardial infarction, coronary revascularization, pacemakers/defibrillators, and diabetes mellitus, p < 0.009 for all). Patients were followed for 28.3 ± 27.2 months, during which 27 events (17 deaths, 10 HF hospitalizations) occurred. Postprocedural MR reduction (MR grade p = 0.487) and freedom from HF hospitalization/death (log-rank: p = 0.811) were similar at 2 years. On multivariable Cox analysis, EuroSCORE-II (adj.HR 1.07 [95%CI: 1.00–1.13], p = 0.027) and residual MR (adj.HR 1.85 [95%CI: 1.17–2.92], p = 0.009) remained significantly associated with outcome. Conclusions. In this propensity-matched, all-comers cohort, two-year outcomes after TMVR versus SMV were similar. Given the reported favorable long-term durability of TMVR, the interventional approach emerges as a valuable alternative for a substantial number of patients with functional and degenerative MR.

The complex anatomy and physiology of the right ventricle (RV) is a major limitation of visual echocardiographic gradation of RV systolic function (RVF). The aim of this study was to compare visual assessment (“eyeballing”) of RVF with gold standard magnetic resonance imaging (MRI)-derived right ventricular ejection fraction (RVEF). Medical professionals from a range of clinical settings and with varying degrees of echocardiography experience were recruited via an online ultrasound teaching platform. In an anonymized web-based test, participants graded RVF in 10 patients with varying degrees of RVF via “eyeballing” of an RV-focused four-chamber view. Two skills were evaluated: (1) ability to differentiate between normal and reduced RVF; and (2) ability to determine the correct degree of RV systolic dysfunction. A total of 868 participants from 99 countries were included. For detection of reduced RVF (MRI-RVEF 40% of cases. In the present cohort, “eyeballing” was associated with excellent sensitivity but poor specificity in terms of differentiation between normal and abnormal RVF. Even among experts, classification of the degree of RV dysfunction was imprecise. In accordance with current guidelines, the present data suggest that “eyeballing” should be combined with evaluation of other echocardiographic parameters of RVF.

Background: Left ventricular (LV) dilatation is a key compensatory feature in patients with chronic aortic regurgitation (AR). However, sex-differences in LV remodeling and outcomes in chronic AR have been poorly investigated so far. Methods: We performed cardiovascular magnetic resonance imaging (CMR) including phase-contrast velocity-encoded imaging for the measurement of regurgitant fraction (RegF) at the sinotubular junction, in consecutive patients with at least mild AR on echocardiography. We assessed LV size (end-diastolic volume indexed to body surface area, LVEDV/BSA) and investigated sex differences between LV remodeling and increasing degrees of AR severity. Cox-regression models were used to test differences in outcomes between men and women using a composite of heart failure hospitalization, unscheduled AR intervention, and cardiovascular death. Results: 270 consecutive patients (59.6% male, 59.8 &plusmn, 20.8 y/o, 59.6% with at least moderate AR on echocardiography) were included. On CMR, mean RegF was 18.1 &plusmn, 17.9% and a total of 65 (24.1%) had a RegF &ge, 30%. LVEDV/BSA was markedly closer related with AR severity (RegF) in men compared to women. Each 1-SD increase in LVEDV/BSA (mL/m2) was associated with a 9.7% increase in RegF in men and 5.9% in women, respectively (p-value for sex-interaction &lt, 0.001). Based on previously published reference values, women&mdash, in contrast to men&mdash, frequently had a normal LV size despite severe AR (e.g., for LVEDV/BSA on CMR: 35.3% versus 8.7%, p &lt, 0.001). In a Cox-regression model adjusted for age, LVEDV/BSA and RegF, women were at significantly higher risk for the composite endpoint when compared to men (adj. HR 1.81 (95%CI 1.09&ndash, 3.03), p = 0.022). Conclusion: In patients with chronic AR, LV remodeling is a hallmark feature in men but not in women. Severity of AR may be underdiagnosed in female patients in the absence of LV dilatation. Future studies need to address the dismal prognosis in female patients with chronic AR.

Previous studies suggested an association between heart failure (HF) and hepatic disorders. Liver function parameters have been shown to predict outcome in HF with reduced ejection fraction, but their impact in HF with preserved ejection fraction (HFpEF) has not yet been investigated. Between January 2011 and February 2017, 274 patients with confirmed HFpEF were enrolled (age 71.3 ± 8.4 years, 69.3% female) in a prospective registry. During a median follow-up of 21.5 ± 18.6 months, 97 patients (35.4%) reached the combined endpoint defined as hospitalization due to HF and/ or death from any cause. By multivariable cox regression, serum gamma-glutamyltransferase (GT) was independently associated with outcome (Hazard Ratio (HR) 1.002, p = 0.004) along with N-terminal pro brain natriuretic peptide (HR 2.213, p = 0.001) and hemoglobin (HR 0.840, p = 0.006). Kaplan-Meier analysis showed that patients with serum gamma-GT levels above a median of 36 U/L had significantly more events as compared to the remainder of the group (log-rank p = 0.012). By multivariable logistic regression, higher early mitral inflow velocity/ mitral peak velocity of late filling (Odds Ratio (OR) 2.173, p = 0.024), higher right atrial (RA) pressure (OR 1.139, p 36 U/L. Serum levels of gamma-GT are associated with both left and right-sided cardiac alterations and may serve as a simple tool for risk prediction in HFpEF, especially when further diagnostic modalities are not available.

Aims. Two thirds of patients with heart failure and preserved ejection fraction (HFpEF) have an indication for oral anticoagulation (OAC) to prevent thromboembolic events. However, evidence regarding the safety of OAC in HFpEF is limited. Therefore, our aim was to describe bleeding events and to find predictors of bleeding in a large HFpEF cohort. Methods and Results. We recorded bleeding events in a prospective HFpEF cohort. Out of 328 patients (median age 71 years (interquartile range (IQR) 67&ndash, 77)), 64.6% (n = 212) were treated with OAC. Of those, 65.1% (n = 138) received vitamin-K-antagonists (VKA) and 34.9% (n = 72) non-vitamin K oral anticoagulants (NOACs). During a median follow-up time of 42 (IQR 17&ndash, 63) months, a total of 54 bleeding events occurred. Patients on OAC experienced more bleeding events (n = 49 (23.1%) versus n = 5 (4.3%), p &lt, 0.001). Major drivers of events were gastrointestinal (GI) bleeding (n = 18 (36.7%)]. HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score (hazard ratios (HR) of 2.15 (95% confidence interval (CI) 1.65&ndash, 2.79, p &lt, 0.001)) was the strongest independent predictor for overall bleeding. In the subgroup of GI bleeding, mean right atrial pressure (mRAP: HR of 1.13 (95% CI 1.03&ndash, 1.25, p = 0.013)) and HAS-BLED score (HR of 1.74 (95% CI 1.15&ndash, 2.64, p = 0.009)] remained significantly associatiated with bleeding events after adjustment. mRAP provided additional prognostic value beyond the HAS-BLED score with an improvement from 0.63 to 0.71 (95% CI 0.58&ndash, 0.84, p for comparison 0.032), by C-statistic. This additional prognostic value was confirmed by significant improvements in net reclassification index (61.3%, p = 0.019) and integrated discrimination improvement (3.4%, p = 0.015). Conclusion. OAC-treated HFpEF patients are at high risk of GI bleeding. High mRAP as an indicator of advanced stage of disease was predictive for GI bleeding events and provided additional risk stratification information beyond that obtained by HAS-BLED score.

Purpose of the present cohort study was the determination of lower body function and rotation in patients with symptomatic component mal-rotation after total knee arthroplasty using instrumented 3D gait analysis. A consecutive series of 12 patients (61.3 years ± 11.4 years) were included suffering under remaining pain or limited range of motion at least six months after total knee arthroplasty. A CT-scan according to the protocol of Berger et al. and instrumented 3D gait analysis were carried out including clinical examination, videotaping, and kinematic analysis using a Plug-in Gait model. Outcome variables were temporospatial parameters as well as kinematics in sagittal and transversal plane. Data for reference group were collected retrospectively and matched by age and gender. Temporospatial parameters of the study group showed decreased velocity, cadence, and step length as well as increased step time. Single limb support was reduced for the affected limb. In sagittal plane, maximum knee flexion during swing phase was reduced for the replaced knee joint. In transverse plane, there was hardly any difference between affected and non-affected limb. Compared to the reference group, both limbs show significant increased internal ankle rotation and external hip rotation. There were significant strong linear correlations between ankle rotation and hip rotation as well as ankle rotation and radiological tibial mal-rotation. Patients with symptomatic component mal-rotation after total knee arthroplasty showed typically functional deficits. The affected and non-affected limb showed significant increased internal ankle rotation and external hip rotation, while only the affected, replaced knee showed reduced internal knee rotation. Identification of rotational abnormalities of hip and ankle joints seems to be mandatory in TKA to identify the patient group with external hip rotation, internal ankle rotation, and an elevated risk for symptomatic rotational TKA component mal-alignment.

Objectives This study sought to compare the prognostic power of left ventricular end-diastolic pressure (LVEDP) and pulmonary arterial wedge pressure (PAWP) in heart failure with preserved ejection fraction (HFpEF).

Purpose. Heme oxygenase-1 (HO-1) has been proposed to exert pharmacological benefits by its antioxidative and anti-inflammatory effects. HO-1 expression may be affected by the GT length polymorphism in the promoter region of the HO-1 gene. We investigated the inducibility of HO-1 by orally administered curcumin in healthy male subjects and its correlation with the GT length polymorphism.Methods.In an open label uncontrolled phase-1 pilot study, ten male subjects received 12 g of oral curcumin. To investigate the effects of the GT length polymorphism on the inducibility of HO-1, five subjects with homozygous short and five with homozygous long GT genotypes were studied. Plasma concentrations of curcumin, bilirubin, HO-1 mRNA, and protein expression in peripheral blood mononuclear cells (PBMCs) were analyzed over 48 hours.Results.At a detection limit of 1 µg/mL curcumin could not be detected in plasma of any subject. Compared to baseline, HO-1 mRNA and protein levels were not induced in PBMCs at any time point up to 48 hours. There was no correlation between any of the parameters and GT length polymorphism.Conclusions. Oral curcumin administration has low bioavailability and does not induce HO-1 on mRNA or protein level in PBMCs.

To improve the signal to noise level, devices for optical and x-ray astronomy use techniques to suppress background events. Well known examples are e.g. shutters or frame-store Charge Coupled Devices (CCDs). Based on the DEpleted P-channel Field Effect Transistor (DEPFET) principle a so-called Gatebale DEPFET detector can be built. Those devices combine the DEPFET principle with a fast built-in electronic shutter usable for optical and x-ray applications. The DEPFET itself is the basic cell of an active pixel sensor build on a fully depleted bulk. It combines internal amplification, readout on demand, analog storage of the signal charge and a low readout noise with full sensitivity over the whole bulk thickness. A Gatebale DEPFET has all these benefits and obviates the need for an external shutter. Two concepts of Gatebale DEPFET layouts providing a built-in shutter will be introduced. Furthermore proof of principle measurements for both concepts are presented. Using recently produced prototypes a shielding of the collection anode up to 1 • 10 −4 was achieved. Predicted by simulations, an optimized geometry should result in values of 1 • 10 −5 and better. With the switching electronic currently in use a timing evaluation of the shutter opening and closing resulted in rise and fall times of 100ns.

One of the X-ray imaging detectors in development for the European XFEL (X-ray Free Electron Laser) is the DSSC (DEPFET Sensor with Signal Compression). The DSSC sensor array will have a format of 1024 × 1024 pixels with a pixel size in the order of 200 µm. It is optimized for the detection of low-energy X-ray photons and designed to operate at frame rates up to 4.5 MHz with a dynamic range of several thousand photons per pixel and frame and single photon resolution at small photon numbers. The DSSC system's core component is an active pixel sensor based on the DEPFET (DEpleted P-channel Field Effect Transistor) structure. A DEPFET is an integrated detector-amplifier combining internal amplification, full sensitivity over the whole bulk thickness, analog data storage, readout on demand, low serial noise, and absence of reset noise. For the DSSC-adaptation of the DEPFET principle the new feature of signal compression has been added, i.e. the device has a high gain at small signals and a reduced gain at large signals. With this strongly non-linear response the DSSC-DEPFET provides the required high charge handling capacity with simultaneous single photon resolution for low-energy X-rays. This paper presents the concept of the DSSC-DEPFET. Its functionality is demonstrated by measurements of a first series of prototypes.

PurposeMild therapeutic hypothermia proved to be beneficial when induced after cardiac arrest in humans. Prehospital cooling with i.v. fluids was associated with adverse side effects. Our primary objective was to compare time to target temperature of out-of hospital cardiac arrest patients cooled non-invasively either in the prehospital setting vs. the in-hospital (IH) setting, to assess surface-cooling safety profile and long term outcome.MethodsIn this retrospective, single center cohort study, a group of adult patients with restoration of spontaneous circulation (ROSC) after out-of hospital cardiac arrest were cooled with a surface cooling pad beginning either in the prehospital or IH setting for 24h. Time to target temperature (33.9°C), temperature on admission, time to admission after ROSC and outcome were compared. Also, rearrests and pulmonary edema were assessed. Neurologic outcome at 12 months was evaluated (Cerebral Performance Category, CPC 1–2, favorable outcome).ResultsBetween September 2005 and February 2010, 56 prehospital cooled patients and 54 IH-cooled patients were treated. Target temperature was reached in 85 (66–117)min (prehospital) and in 135 (102–192)min (IH) after ROSC (p

Background Accumulation of diffuse myocardial fibrosis / extracellular volume (ECV) in the myocardium is common to various cardiac diseases and is associated with an unfavorable prognosis. Various cardiac magnetic resonance (CMR) T1 mapping techniques have recently been proposed for the quantification of ECV, including: 1. Modified Look-Locker Inversion recovery (MOLLI) T1 mapping including calculation of ECV, 2. Post-contrast multiple-breath-hold T1 mapping. 3. Native (precontrast) T1 mapping. T1 mapping is a promising technique, however, validation data based on myocardial biopsy are sparse. Methods 36 heart failure patients underwent CMR T1 mapping and left-ventricular biopsy within 4 weeks. CMR protocols (1.5-T scanner, (Magnetom Avanto, Siemens Healthcare, Erlangen, Germany) included non-product MOLLI and multiple-breath-hold T1 mapping. The population consisted of 22 patients with HFpEF (heart failure with preserved ejection fraction), 7 with cardiac amyloidosis, 3 with HFrEF (heart failure with reduced ejection fraction) and 4 with organic mitral regurgitation (MR). Specimens were stained using modified Trichrome. TissueFAXS and dedicated software were used to quantify ECV. Results ECV by TissueFAXS was 32±17% and 35±13% by CMR MOLLI. Post-contrast T1 times by the multiple-breathhold sequence were 411±79ms, native T1 times were 1009±73ms. Patients with amyloidosis had significantly more ECV by TissueFAXS (59±13%, p