Stiffness pulsation of the human brain detected by non-invasive time-harmonic elastography.

Introduction: Cerebral pulsation is a vital aspect of cerebral hemodynamics. Changes in arterial pressure in response to cardiac pulsation cause cerebral pulsation, which is related to cerebrovascular compliance and cerebral blood perfusion. Cerebrovascular compliance and blood perfusion influence the mechanical properties of the brain, causing pulsation-induced changes in cerebral stiffness. However, there is currently no imaging technique available that can directly quantify the pulsation of brain stiffness in real time. Methods: Therefore, we developed non-invasive ultrasound time-harmonic elastography (THE) technique for the real-time detection of brain stiffness pulsation. We used state-of-the-art plane-wave imaging for interleaved acquisitions of shear waves at a frequency of 60 Hz to measure stiffness and color flow imaging to measure cerebral blood flow within the middle cerebral artery. In the second experiment, we used cost-effective lineby-line B-mode imaging to measure the same mechanical parameters without flow imaging to facilitate future translation to the clinic. Results: In 10 healthy volunteers, stiffness increased during the passage of the arterial pulse wave from 4.8% ± 1.8% in the temporal parenchyma to 11% ± 5% in the basal cisterns and 13% ± 9% in the brain stem. Brain stiffness peaked in synchrony with cerebral blood flow at approximately 180 ± 30 ms after the cardiac R-wave. Line-by-line THE provided the same stiffness values with similar time resolution as high-end plane-wave THE, demonstrating the robustness of brain stiffness pulsation as an imaging marker. Discussion: Overall, this study sets the background and provides reference values for time-resolved THE in the human brain as a cost-efficient and easy-touse mechanical biomarker associated with cerebrovascular compliance.

Valsalva Maneuver Decreases Liver and Spleen Stiffness Measured by Time-Harmonic Ultrasound Elastography.

Ultrasound elastography quantitatively measures tissue stiffness and is widely used in clinical practice to diagnose various diseases including liver fibrosis and portal hypertension. The stiffness of soft organs has been shown to be sensitive to blood flow and pressure-related diseases such as portal hypertension. Because of the intricate coupling between tissue stiffness of abdominal organs and perfusion-related factors such as vascular stiffness or blood volume, simple breathing maneuvers have altered the results of liver elastography, while other organs such as the spleen are understudied. Therefore, we investigated the effect of a standardized Valsalva maneuver on liver stiffness and, for the first time, on spleen stiffness using time-harmonic elastography (THE). THE acquires full-field-of-view stiffness maps based on shear wave speed (SWS), covers deep tissues, and is potentially sensitive to SWS changes induced by altered abdominal pressure in the hepatosplenic system. SWS of the liver and the spleen was measured in 17 healthy volunteers under baseline conditions and during the Valsalva maneuver. With the Valsalva maneuver, SWS in the liver decreased by 2.2% (from a median of 1.36 m/s to 1.32 m/s; p = 0.021), while SWS in the spleen decreased by 5.2% (from a median of 1.63 m/s to 1.51 m/s; p = 0.00059). Furthermore, we observed that the decrease was more pronounced the higher the baseline SWS values were. In conclusion, the results confirm our hypothesis that the Valsalva maneuver decreases liver and spleen stiffness, showing that THE is sensitive to perfusion pressure-related changes in tissue stiffness. With its extensive organ coverage and high penetration depth, THE may facilitate translation of pressure-sensitive ultrasound elastography into clinical routine.

Efficacy of telemedical interventional management in patients with heart failure (TIM-HF2): a randomised, controlled, parallel-group, unmasked trial.

BACKGROUND: Remote patient management in patients with heart failure might help to detect early signs and symptoms of cardiac decompensation, thus enabling a prompt initiation of the appropriate treatment and care before a full manifestation of a heart failure decompensation. We aimed to investigate the efficacy of our remote patient management intervention on mortality and morbidity in a well defined heart failure population. METHODS: The Telemedical Interventional Management in Heart Failure II (TIM-HF2) trial was a prospective, randomised, controlled, parallel-group, unmasked (with randomisation concealment), multicentre trial with pragmatic elements introduced for data collection. The trial was done in Germany, and patients were recruited from hospitals and cardiology practices. Eligible patients had heart failure, were in New York Heart Association class II or III, had been admitted to hospital for heart failure within 12 months before randomisation, and had a left ventricular ejection fraction (LVEF) of 45% or lower (or if higher than 45%, oral diuretics were being prescribed). Patients with major depression were excluded. Patients were randomly assigned (1:1) using a secure web-based system to either remote patient management plus usual care or to usual care only and were followed up for a maximum of 393 days. The primary outcome was percentage of days lost due to unplanned cardiovascular hospital admissions or all-cause death, analysed in the full analysis set. Key secondary outcomes were all-cause and cardiovascular mortality. This study is registered with ClinicalTrials.gov, number NCT01878630, and has now been completed. FINDINGS: Between Aug 13, 2013, and May 12, 2017, 1571 patients were randomly assigned to remote patient management (n=796) or usual care (n=775). Of these 1571 patients, 765 in the remote patient management group and 773 in the usual care group started their assigned care, and were included in the full analysis set. The percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause death was 4·88% (95% CI 4·55-5·23) in the remote patient management group and 6·64% (6·19-7·13) in the usual care group (ratio 0·80, 95% CI 0·65-1·00; p=0·0460). Patients assigned to remote patient management lost a mean of 17·8 days (95% CI 16·6-19·1) per year compared with 24·2 days (22·6-26·0) per year for patients assigned to usual care. The all-cause death rate was 7·86 (95% CI 6·14-10·10) per 100 person-years of follow-up in the remote patient management group compared with 11·34 (9·21-13·95) per 100 person-years of follow-up in the usual care group (hazard ratio [HR] 0·70, 95% CI 0·50-0·96; p=0·0280). Cardiovascular mortality was not significantly different between the two groups (HR 0·671, 95% CI 0·45-1·01; p=0·0560). INTERPRETATION: The TIM-HF2 trial suggests that a structured remote patient management intervention, when used in a well defined heart failure population, could reduce the percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause mortality. FUNDING: German Federal Ministry of Education and Research.

Prognostic value of serial six-minute walk tests using tele-accelerometry in patients with chronic heart failure: A pre-specified sub-study of the TIM-HF-Trial.

BACKGROUND: The six-minute walk test (6MWT) is an established functional test assessing exercise capacity and is used to predict clinical prognosis in patients with chronic heart failure (HF). Tele-accelerometry is a novel approach to activity monitoring using telemedical data transfer and allows a Tele-6MWT to be performed in an outpatient setting. It offers patients the option of performing simple serial follow-up tests in their own home. AIMS: The aim of this study was to investigate the prognostic value of serial Tele-6MWTs using tele-accelerometry in patients with HF. DESIGN/METHODS: In this proof-of-concept study, 155 patients with HF completed the Tele-6MWT in an outdoor setting once per month over a period of 0.25-21 months. We analysed the differences in the number of steps over time to predict hospitalization as a result of HF or death. RESULTS: Patients with at least one event (n = 31) recorded a lower number of steps and a shorter distance in Tele-6MWT at baseline compared with patients who remained event-free (n = 124) (540.1 ± 78.4 steps vs. 601.8 ± 76.7 steps, P < 0.001 respectively; 353.2 ± 82.4 m vs. 418.8 ± 95.6 m, P < 0.001). Patients (n = 19) who performed more than one Tele-6MWT prior to a clinical event showed no significant difference in the number of steps, regardless of whether the baseline test was compared with the last Tele-6MWT before the event or with the last two tests before the event. CONCLUSION: Tele-6MWT has a high predictive value with respect to hospitalization as a result of HF or death from any cause and the results were comparable with the prognostic impact of a conventional 6MWT. Therefore Tele-6MWT may be used as alternative test method in the home environment. However, there is no added prognostic value of repeating Tele-6MWTs on a monthly basis.