Monitoring LVAD parameters to detect flow-and power-impacting complications: A proof-of-concept

The number of patients on left ventricular assist device (LVAD) support increases due to the growing number of patients with end-stage heart failure and the limited number of donor hearts. Despite improving survival rates, patients frequently suffer from adverse events such as cardiac arrythmia and major bleeding. Telemonitoring is a potentially powerful tool to early detect deteriorations and may further improve outcome after LVAD implantation. Hence, we developed a personalized algorithm to remotely monitor HeartMate3 (HM3) pump parameters aiming to early detect unscheduled admissions due to cardiac arrythmia or major bleeding. The source code of the algorithm made publicly available. The algorithm was optimized and tested retrospectively using HM3 power and flow data of 120 patients, including 29 admissions due to cardiac arrythmia and 14 admissions due to major bleeding. Using a true alarm window of 14 days prior to the admission date, the algorithm detected 59% and 79% of unscheduled admissions due to cardiac arrythmia and major bleeding, respectively, with a false alarm rate of 2%. The proposed algorithm showed that the personalized algorithm is a viable approach to early identify cardiac arrythmia and major bleeding by monitoring HM3 pump parameters. External validation is needed and integration with other clinical parameters could potentially improve the predictive value. In addition, the algorithm can be further enhanced using continuous data

Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support

Background: Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR). Methods: 18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1–2 weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation. Results: A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p < 0.001–0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p < 0.001–0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p = 0.19). Conclusions: A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms

Patients with diffuse idiopathic skeletal hyperostosis have an increased burden of thoracic aortic calcifications

OBJECTIVES: DISH has been associated with increased coronary artery calcifications and incident ischaemic stroke. The formation of bone along the spine may share pathways with calcium deposition in the aorta. We hypothesized that patients with DISH have increased vascular calcifications. Therefore we aimed to investigate the presence and extent of DISH in relation to thoracic aortic calcification (TAC) severity. METHODS: This cross-sectional study included 4703 patients from the Second Manifestation of ARTerial disease cohort, consisting of patients with cardiovascular events or risk factors for cardiovascular disease. Chest radiographs were scored for DISH using the Resnick criteria. Different severities of TAC were scored arbitrarily from no TAC to mild, moderate or severe TAC. Using multivariate logistic regression, the associations between DISH and TAC were analysed with adjustments for age, sex, BMI, diabetes, smoking status, non-high-density lipoprotein cholesterol, cholesterol lowering drug usage, renal function and blood pressure. RESULTS: A total of 442 patients (9.4%) had evidence of DISH and 1789 (38%) patients had TAC. The prevalence of DISH increased from 6.6% in the no TAC group to 10.8% in the mild, 14.3% in the moderate and 17.1% in the severe TAC group. After adjustments, DISH was significantly associated with the presence of TAC [odds ratio (OR) 1.46 [95% CI 1.17, 1.82)]. In multinomial analyses, DISH was associated with moderate TAC [OR 1.43 (95% CI 1.06, 1.93)] and severe TAC [OR 1.67 (95% CI 1.19, 2.36)]. CONCLUSIONS: Subjects with DISH have increased TACs, providing further evidence that patients with DISH have an increased burden of vascular calcifications

Cohort profile: the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study-an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands

PURPOSE: The Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date. PARTICIPANTS: The UCC-SMART Study includes patients aged 18-90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima-media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee. FINDINGS TO DATE: By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines. FUTURE PLANS: The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes

Diffuse idiopathic skeletal hyperostosis is associated with incident stroke in patients with increased cardiovascular risk

OBJECTIVES: Earlier retrospective studies have suggested a relation between DISH and cardiovascular disease, including myocardial infarction. The present study assessed the association between DISH and incidence of cardiovascular events and mortality in patients with high cardiovascular risk. METHODS: In this prospective cohort study, we included 4624 patients (mean age 58.4 years, 69.6% male) from the Second Manifestations of ARTerial disease cohort. The main end point was major cardiovascular events (MACE: stroke, myocardial infarction and vascular death). Secondary endpoints included all-cause mortality and separate vascular events. Cause-specific proportional hazard models were used to evaluate the risk of DISH on all outcomes, and subdistribution hazard models were used to evaluate the effect of DISH on the cumulative incidence. All models were adjusted for age, sex, body mass index, blood pressure, diabetes, non-HDL cholesterol, packyears, renal function and C-reactive protein. RESULTS: DISH was present in 435 (9.4%) patients. After a median follow-up of 8.7 (IQR 5.0–12.0) years, 864 patients had died and 728 patients developed a MACE event. DISH was associated with an increased cumulative incidence of ischaemic stroke. After adjustment in cause-specific modelling, DISH remained significantly associated with ischaemic stroke (HR 1.55; 95% CI: 1.01, 2.38), but not with MACE (HR 0.99; 95% CI: 0.79, 1.24), myocardial infarction (HR 0.88; 95% CI: 0.59, 1.31), vascular death (HR 0.94; 95% CI: 0.68, 1.27) or all-cause mortality (HR 0.94; 95% CI: 0.77, 1.16). CONCLUSIONS: The presence of DISH is independently associated with an increased incidence and risk for ischaemic stroke, but not with MACE, myocardial infarction, vascular death or all-cause mortality

A computerised decision support system for cardiovascular risk management ‘live’ in the electronic health record environment: development, validation and implementation—the Utrecht Cardiovascular Cohort Initiative

PURPOSE: We set out to develop a real-time computerised decision support system (CDSS) embedded in the electronic health record (EHR) with information on risk factors, estimated risk, and guideline-based advice on treatment strategy in order to improve adherence to cardiovascular risk management (CVRM) guidelines with the ultimate aim of improving patient healthcare. METHODS: We defined a project plan including the scope and requirements, infrastructure and interface, data quality and study population, validation and evaluation of the CDSS. RESULTS: In collaboration with clinicians, data scientists, epidemiologists, ICT architects, and user experience and interface designers we developed a CDSS that provides ‘live’ information on CVRM within the environment of the EHR. The CDSS provides information on cardiovascular risk factors (age, sex, medical and family history, smoking, blood pressure, lipids, kidney function, and glucose intolerance measurements), estimated 10-year cardiovascular risk, guideline-compliant suggestions for both pharmacological and non-pharmacological treatment to optimise risk factors, and an estimate on the change in 10-year risk of cardiovascular disease if treatment goals are adhered to. Our pilot study identified a number of issues that needed to be addressed, such as missing data, rules and regulations, privacy, and patient participation. CONCLUSION: Development of a CDSS is complex and requires a multidisciplinary approach. We identified opportunities and challenges in our project developing a CDSS aimed at improving adherence to CVRM guidelines. The regulatory environment, including guidance on scientific evaluation, legislation, and privacy issues needs to evolve within this emerging field of eHealth

Exogenous surfactant application in a rat lung ischemia reperfusion injury model: effects on edema formation and alveolar type II cells

<p>Abstract</p> <p>Background</p> <p>Prophylactic exogenous surfactant therapy is a promising way to attenuate the ischemia and reperfusion (I/R) injury associated with lung transplantation and thereby to decrease the clinical occurrence of acute lung injury and acute respiratory distress syndrome. However, there is little information on the mode by which exogenous surfactant attenuates I/R injury of the lung. We hypothesized that exogenous surfactant may act by limiting pulmonary edema formation and by enhancing alveolar type II cell and lamellar body preservation. Therefore, we investigated the effect of exogenous surfactant therapy on the formation of pulmonary edema in different lung compartments and on the ultrastructure of the surfactant producing alveolar epithelial type II cells.</p> <p>Methods</p> <p>Rats were randomly assigned to a control, Celsior (CE) or Celsior + surfactant (CE+S) group (n = 5 each). In both Celsior groups, the lungs were flush-perfused with Celsior and subsequently exposed to 4 h of extracorporeal ischemia at 4°C and 50 min of reperfusion at 37°C. The CE+S group received an intratracheal bolus of a modified natural bovine surfactant at a dosage of 50 mg/kg body weight before flush perfusion. After reperfusion (Celsior groups) or immediately after sacrifice (Control), the lungs were fixed by vascular perfusion and processed for light and electron microscopy. Stereology was used to quantify edematous changes as well as alterations of the alveolar epithelial type II cells.</p> <p>Results</p> <p>Surfactant treatment decreased the intraalveolar edema formation (mean (coefficient of variation): CE: 160 mm³(0.61) vs. CE+S: 4 mm³(0.75); p < 0.05) and the development of atelectases (CE: 342 mm³(0.90) vs. CE+S: 0 mm³; p < 0.05) but led to a higher degree of peribronchovascular edema (CE: 89 mm³(0.39) vs. CE+S: 268 mm³(0.43); p < 0.05). Alveolar type II cells were similarly swollen in CE (423 μm³(0.10)) and CE+S (481 μm³(0.10)) compared with controls (323 μm³(0.07); p < 0.05 vs. CE and CE+S). The number of lamellar bodies was increased and the mean lamellar body volume was decreased in both CE groups compared with the control group (p < 0.05).</p> <p>Conclusion</p> <p>Intratracheal surfactant application before I/R significantly reduces the intraalveolar edema formation and development of atelectases but leads to an increased development of peribronchovascular edema. Morphological changes of alveolar type II cells due to I/R are not affected by surfactant treatment. The beneficial effects of exogenous surfactant therapy are related to the intraalveolar activity of the exogenous surfactant.</p

Activation of TRPC6 channels is essential for lung ischaemia–reperfusion induced oedema in mice

Lung ischaemia–reperfusion-induced oedema (LIRE) is a life-threatening condition that causes pulmonary oedema induced by endothelial dysfunction. Here we show that lungs from mice lacking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox2y/−) or the classical transient receptor potential channel 6 (TRPC6−/−) are protected from LIR-induced oedema (LIRE). Generation of chimeric mice by bone marrow cell transplantation and endothelial-specific Nox2 deletion showed that endothelial Nox2, but not leukocytic Nox2 or TRPC6, are responsible for LIRE. Lung endothelial cells from Nox2- or TRPC6-deficient mice showed attenuated ischaemia-induced Ca2+ influx, cellular shape changes and impaired barrier function. Production of reactive oxygen species was completely abolished in Nox2y/− cells. A novel mechanistic model comprising endothelial Nox2-derived production of superoxide, activation of phospholipase C-γ, inhibition of diacylglycerol (DAG) kinase, DAG-mediated activation of TRPC6 and ensuing LIRE is supported by pharmacological and molecular evidence. This mechanism highlights novel pharmacological targets for the treatment of LIRE