The role of non-invasive devices for the telemonitoring of heart failure patients

Heart failure (HF) patients represent one of the most prevalent as well as one of the most fragile population encountered in the cardiology and internal medicine departments nowadays. Estimated to account for around 26 million people worldwide, diagnosed patients present a poor prognosis and quality of life with a clinical history accompanied by repeated hospital admissions caused by an exacerbation of their chronic condition. The frequent hospitalizations and the extended hospital stays mean an extremely high economic burden for healthcare institutions. Meanwhile, the number of chronically diseased and elderly patients is continuously rising, and a lack of specialized physicians is evident. To cope with this health emergency, more efficient strategies for patient management, more accurate diagnostic tools, and more efficient preventive plans are needed. In recent years, telemonitoring has been introduced as the potential answer to solve such needs. Different methodologies and devices have been progressively investigated for effective home monitoring of cardiologic patients. Invasive hemodynamic devices, such as CardioMEMS™, have been demonstrated to be reducing hospitalizations and mortality, but their use is however restricted to limited cases. The role of external non-invasive devices for remote patient monitoring, instead, is yet to be clarified. In this review, we summarized the most relevant studies and devices that, by utilizing non-invasive telemonitoring, demonstrated whether beneficial effects in the management of HF patients were effective

Cardiovascular magnetic resonance feature tracking in pigs: a reproducibility and sample size calculation study

Cardiovascular magnetic resonance feature tracking (CMR-FT) is a novel technique for non-invasive assessment of myocardial motion and deformation. Although CMR-FT is standardized in humans, literature on comparative analysis from animal models is scarce. In this study, we measured the reproducibility of global strain under various inotropic states and the sample size needed to test its relative changes in pigs. Ten anesthetized healthy Landrace pigs were investigated. After baseline (BL), two further steps were performed: (I) dobutamine-induced hyper-contractility (Dob) and (II) verapamil-induced hypocontractility (Ver). Global longitudinal (GLS), circumferential (GCS) and radial strain (GRS) were assessed. This study shows a good to excellent inter- and intra-observer reproducibility of CMR-FT in pigs under various inotropic states. The highest inter-observer reproducibility was observed for GLS at both BL (ICC 0.88) and Ver (ICC 0.79). According to the sample size calculation for GLS, a small number of animals could be used for future trials

Nitric oxide metabolites: associations with cardiovascular biomarkers and clinical parameters in patients with HFpEF

AIMS: Heart failure with preserved ejection fraction (HFpEF) is one of the most rapidly growing cardiovascular health burden worldwide, but there is still a lack of understanding about the HFpEF pathophysiology. The nitric oxide (NO) signalling pathway has been identified as a potential key element. The aim of our study was to investigate markers of NO metabolism [ l-arginine ( l-Arg), homoarginine (hArg), and asymmetric and symmetric dimethylarginine (ADMA and SDMA)], additional biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), endothelin-1 (ET-1), mid-regional pro-adrenomedullin (MR-proADM), copeptin, and high-sensitivity C-reactive protein (hsCRP)], and the endothelial function in an integrated approach focusing on associations with clinical characteristics in patients with HFpEF. METHODS AND RESULTS: Seventy-three patients, prospectively enrolled in the 'German HFpEF Registry', were analysed. Inclusion criteria were left ventricular ejection fraction (LVEF) ≥ 50%; New York Heart Association functional class ≥ II; elevated levels of NT-proBNP > 125 pg/mL; and at least one additional criterion for structural heart disease or diastolic dysfunction. All patients underwent transthoracic echocardiography, cardiopulmonary exercise testing, and pulse amplitude tonometry (EndoPAT™). Patients were categorized in two groups based on their retrospectively calculated HFA-PEFF score. Serum concentrations of l-Arg, hArg, ADMA, SDMA, NT-proBNP, ET-1, MR-proADM, copeptin, and hsCRP were determined. Patients had a median age of 74 years, 47% were female, and median LVEF was 57%. Fifty-two patients (71%) had an HFA-PEFF score ≥ 5 (definitive HFpEF), and 21 patients (29%) a score of 3 to 4 (risk for HFpEF). Overall biomarker concentrations were 126 ± 32 μmol/L for l-Arg, 1.67 ± 0.55 μmol/L for hArg, 0.74 (0.60;0.85) μmol/L for SDMA, and 0.61 ± 0.10 μmol/L for ADMA. The median reactive hyperaemia index (RHI) was 1.55 (1.38;1.87). SDMA correlated with NT-proBNP (r = 0.291; P = 0.013), ET-1 (r = 0.233; P = 0.047), and copeptin (r = 0.381; P = 0.001). ADMA correlated with ET-1 (r = 0.250; P = 0.033) and hsCRP (r = 0.303; P = 0.009). SDMA was associated with the left atrial volume index (β = 0.332; P = 0.004), also after adjustment for age, sex, and comorbidities. Biomarkers were non-associated with the RHI. A principal component analysis revealed two contrary clusters of biomarkers. CONCLUSIONS: Our findings suggest an impaired NO metabolism as one possible key pathogenic determinant in at least a subgroup of patients with HFpEF. We argue for further evaluation of NO-based therapies. Upcoming studies should clarify whether subgroups of HFpEF patients can take more benefit from therapies that are targeting NO metabolism and pathway

Estimation of total collagen volume: a T1 mapping versus histological comparison study in healthy Landrace pigs

Right ventricular biopsy represents the gold standard for the assessment of myocardial fibrosis and collagen content. This invasive technique, however, is accompanied by perioperative complications and poor reproducibility. Extracellular volume (ECV) measured through cardiovascular magnetic resonance (CMR) has emerged as a valid surrogate method to assess fibrosis non-invasively. Nonetheless, ECV provides an overestimation of collagen concentration since it also considers interstitial space. Our study aims to investigate the feasibility of estimating total collagen volume (TCV) through CMR by comparing it with the TCV measured at histology. Seven healthy Landrace pigs were acutely instrumented closed-chest and transported to the MRI facility for measurements. For each protocol, CMR imaging at 3T was acquired. MEDIS software was used to analyze T1 mapping and ECV for both the left ventricular myocardium (LVmyo) and left ventricular septum (LVseptum). ECV was then used to estimate TCVCMR at LVmyo and LVseptum following previously published formulas. Tissues were prepared following an established protocol and stained with picrosirius red to analyze the TCVhisto in LVmyo and LVseptum. TCV measured at LVmyo and LVseptum with both histology (8 ± 5 ml and 7 ± 3 ml, respectively) and T1-Mapping (9 ± 5 ml and 8 ± 6 ml, respectively) did not show any regional differences. TCVhisto and TCVCMR showed a good level of data agreement by Bland–Altman analysis. Estimation of TCV through CMR may be a promising way to non-invasively assess myocardial collagen content and may be useful to track disease progression or treatment response

Z-score mapping for standardized analysis and reporting of cardiovascular magnetic resonance modified Look-Locker inversion recovery (MOLLI) T1 data: normal behavior and validation in patients with amyloidosis

BACKGROUND: T1 mapping using modified Look-Locker inversion recovery (MOLLI) provides quantitative information on myocardial tissue composition. T1 results differ between sites due to variations in hardware and software equipment, limiting the comparability of results. The aim was to test if Z-scores can be used to compare the results of MOLLI T1 mapping from different cardiovascular magnetic resonance (CMR) platforms. METHODS: First, healthy subjects (n = 15) underwent 11 combinations of native short-axis T1 mapping (four CMR systems from two manufacturers at 1.5 T and 3 T, three MOLLI schemes). Mean and standard deviation (SD) of septal myocardial T1 were derived for each combination. T1 maps were transformed into Z-score maps based on mean and SD values using a prototype post-processing module. Second, Z-score mapping was applied to a validation sample of patients with cardiac amyloidosis at 1.5 T (n = 25) or 3 T (n = 13). RESULTS: In conventional T1 analysis, results were confounded by variations in field strength, MOLLI scheme, and manufacturer-specific system characteristics. Z-score-based analysis yielded consistent results without significant differences between any two of the combinations in part 1 of the study. In the validation sample, Z-score mapping differentiated between patients with cardiac amyloidosis and healthy subjects with the same diagnostic accuracy as standard T1 analysis regardless of field strength. CONCLUSIONS: T1 analysis based on Z-score mapping provides consistent results without significant differences due to field strengths, CMR systems, or MOLLI variants, and detects cardiac amyloidosis with the same diagnostic accuracy as conventional T1 analysis. Z-score mapping provides a means to compare native T1 results acquired with MOLLI across different CMR platforms

Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses fr symptomatic heart failure

AIMS: We performed a randomized, double blind, crossover study of cardiac contractility modulation (CCM) signals in heart failure patients. METHODS AND RESULTS: One hundred and sixty-four subjects with ejection fraction (EF) < 35% and NYHA Class II (24%) or III (76%) symptoms received a CCM pulse generator. Patients were randomly assigned to Group 1 (n = 80, CCM treatment 3 months, sham treatment second 3 months) or Group 2 (n = 84, sham treatment 3 months, CCM treatment second 3 months). The co-primary endpoints were changes in peak oxygen consumption (VO2,peak) and Minnesota Living with Heart Failure Questionnaire (MLWHFQ). Baseline EF (29.3 +/- 6.7% vs. 29.8 +/- 7.8%), VO2,peak (14.1 +/- 3.0 vs. 13.6 +/- 2.7 mL/kg/min), and MLWHFQ (38.9 +/- 27.4 vs. 36.5 +/- 27.1) were similar between the groups. VO2,peak increased similarly in both groups during the first 3 months (0.40 +/- 3.0 vs. 0.37 +/- 3.3 mL/kg/min, placebo effect). During the next 3 months, VO2,peak decreased in the group switched to sham (-0.86 +/- 3.06 mL/kg/min) and increased in patients switched to active treatment (0.16 +/- 2.50 mL/kg/min). MLWHFQ trended better with treatment (-12.06 +/- 15.33 vs. -9.70 +/- 16.71) during the first 3 months, increased during the second 3 months in the group switched to sham (+4.70 +/- 16.57), and decreased further in patients switched to active treatment (-0.70 +/- 15.13). A comparison of values at the end of active treatment periods vs. end of sham treatment periods indicates statistically significantly improved VO2,peak and MLWHFQ (P = 0.03 for each parameter). CONCLUSION: In patients with heart failure and left ventricular dysfunction, CCM signals appear safe; exercise tolerance and quality of life (MLWHFQ) were significantly better while patients were receiving active treatment with CCM for a 3-month period

Pedelec users get more severely injured compared to conventional cyclists

Background For years e-bike (Pedelec) sales have been steadily increasing. Therefore, the incidence of e-bike-related injuries and deaths has been growing. Due to clinical experience, emergency personnel are suspecting that e-bikers might be injured more severely compared to conventional bicyclists suffering from an accident. This topic has not yet been analyzed for Germany. Objective Analysis of injury severity and mortality following e-bike and conventional bicycle accidents in a level I trauma center in Germany. Material and methods Data of patients treated after a bicycle accident at the accident and emergency department as well as the clinic for traumatology and orthopedics of the Evangelical Hospital (Evangelisches Krankenhaus) Oldenburg were gathered from 1 March 2017 to 1 March 2019. Results In this study 59 electric bicycle users (e-bikers) and 164 conventional cyclists were included. The average age of e-bikers was 62 years compared to 48 years in the group of conventional cyclists. Comorbidities were significantly more frequent in the e-bike group compared to classical cyclists. The e-bikers were found to be significantly more severely injured than conventional bicyclists, the mean injury severity scores (ISS) were 5.2 and 3.4, respectively. E-bikers were admitted to the hospital more often and for longer periods than the control group. There was no significant difference in mortality. Conclusion E-bikers are more severely injured in accidents compared to conventional cyclists. Due to older age and comorbidity they form a sensitive trauma subgroup. Based on demographics, an increase of old age, more frail cyclists and a growing incidence of serious e-bike accidents is to be expected. Preventive measures, such as helmet usage and riding lessons should be introduced, especially in e-bikers. E-bikers in the emergency department should be examined and treated with special care and aggressive diagnostics. A low threshold for an initial interdisciplinary assessment (shock room management) is advised

О распределении свинца и хрома в угле основных рабочих пластов Алмазно-Марьевского геолого-промышленного района

Рассмотрены особенности распределения Pb та Cr в угольных пластах Алмазно- Марьевского геолого-промышленного района. Установлен характер распределения, выполнен расчет средневзвешенных концентраций в углях основных пластов и свит, выявлен состав типоморфной геохимической ассоциации Co и V с другими токсичными и потенциальными элементами в углях района. Исследования распределения свинца и хрома в углях основных рабочих пластов Алмазн

K201 improves aspects of the contractile performance of human failing myocardium via reduction in Ca2+ leak from the sarcoplasmic reticulum

In heart failure, intracellular Ca2+ leak from cardiac ryanodine receptors (RyR2s) leads to a loss of Ca2+ from the sarcoplasmic reticulum (SR) potentially contributing to decreased function. Experimental data suggest that the 1,4-benzothiazepine K201 (JTV-519) may stabilise RyR2s and thereby reduce detrimental intracellular Ca2+ leak. Whether K201 exerts beneficial effects in human failing myocardium is unknown. Therefore, we have studied the effects of K201 on muscle preparations from failing human hearts. K201 (0.3 μM; extracellular [Ca2+]e 1.25 mM) showed no effects on contractile function and micromolar concentrations resulted in negative inotropic effects (K201 1 μM; developed tension −9.8 ± 2.5% compared to control group; P < 0.05). Interestingly, K201 (0.3 μM) increased the post-rest potentiation (PRP) of failing myocardium after 120 s, indicating an increased SR Ca2+ load. At high [Ca2+]e concentrations (5 mmol/L), K201 increased PRP already at shorter rest intervals (30 s). Strikingly, treatment with K201 (0.3 μM) prevented diastolic dysfunction (diastolic tension at 5 mmol/L [Ca2+]e normalised to 1 mmol/L [Ca2+]e: control 1.26 ± 0.06, K201 1.01 ± 0.03, P < 0.01). In addition at high [Ca2+]e, K201 (0.3 μM) treatment significantly improved systolic function [developed tension +27 ± 8% (K201 vs. control); P < 0.05]. The beneficial effects on diastolic and systolic functions occurred throughout the physiological frequency range of the human heart rate from 1 to 3 Hz. Upon elevated intracellular Ca2+ concentration, systolic and diastolic contractile functions of terminally failing human myocardium are improved by K201