[The IN-HF Registry: the history and the scientific production for the Italian cardiology community]. / Il programma IN-HF: la storia e la produzione scientifica a favore della comunità cardiologica italiana.

The Italian Network on Congestive Heart Failure (IN-CHF) project, later known as IN-HF Online, was launched in 1995 to provide the Italian cardiology community with a digital tool, standardized across the country, for managing outpatients with heart failure (HF), that enabled the creation of a database for clinical, educational and scientific purposes. During its almost three decades of activity, this observational research program has achieved highly positive scientific results. Indeed, IN-HF fostered professional relationships among individuals working in different centers, established a cultural network for the care of HF patients, periodically updated on the scientific advances, and allowed the assessment of several clinical, epidemiological, and prognostic features. These findings have been published in numerous national and international journals, as summarized in the present overview.

Artificial intelligence, big data and heart transplantation: Actualities.

BACKGROUND: As diagnostic and prognostic models developed by traditional statistics perform poorly in real-world, artificial intelligence (AI) and Big Data (BD) may improve the supply chain of heart transplantation (HTx), allocation opportunities, correct treatments, and finally optimize HTx outcome. We explored available studies, and discussed opportunities and limits of medical application of AI to the field of HTx. METHOD: A systematic overview of studies published up to December 31st, 2022, in English on peer-revied journals, have been identified through PUBMED-MEDLINE-WEB of Science, referring to HTx, AI, BD. Studies were grouped in 4 domains based on main studies' objectives and results: etiology, diagnosis, prognosis, treatment. A systematic attempt was made to evaluate studies by the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD). RESULTS: Among the 27 publications selected, none used AI applied to BD. Of the selected studies, 4 fell in the domain of etiology, 6 in the domain of diagnosis, 3 in the domain of treatment, and 17 in that of prognosis, as AI was most frequently used for algorithmic prediction and discrimination of survival, but in retrospective cohorts and registries. AI-based algorithms appeared superior to probabilistic functions to predict patterns, but external validation was rarely employed. Indeed, based on PROBAST, selected studies showed, to some extent, significant risk of bias (especially in the domain of predictors and analysis). In addition, as example of applicability in the real-world, a free-use prediction algorithm developed through AI failed to predict 1-year mortality post-HTx in cases from our center. CONCLUSIONS: While AI-based prognostic and diagnostic functions performed better than those developed by traditional statistics, risk of bias, lack of external validation, and relatively poor applicability, may affect AI-based tools. More unbiased research with high quality BD meant for AI, transparency and external validations, are needed to have medical AI as a systematic aid to clinical decision making in HTx.

Cardiotoxicity, Cardioprotection, and Prognosis in Survivors of Anticancer Treatment Undergoing Cardiac Surgery: Unmet Needs.

BACKGROUND: Anticancer treatments are improving the prognosis of patients fighting cancer. However, anticancer treatments may also increase the cardiovascular (CV) risk by increasing metabolic disorders. Atherosclerosis and atherothrombosis related to anticancer treatments may lead to ischemic heart disease (IHD), while direct cardiac toxicity may induce non-ischemic heart disease. Moreover, valvular heart disease (VHD), aortic syndromes (AoS), and advanced heart failure (HF) associated with CV risk factors and preclinical CV disease as well as with chronic inflammation and endothelial dysfunction may also occur in survivors of anti-carcer treatments. METHODS: Public electronic libraries have been searched systematically looking at cardiotoxicity, cardioprotection, CV risk and disease, and prognosis after cardiac surgery in survivors of anticancer treatments. RESULTS: CV risk factors and disease may not be infrequent among survivors of anticancer treatments. As cardiotoxicity of established anticancer treatments has been investigated and is frequently irreversible, cardiotoxicity associated with novel treatments appears to be more frequently reversible, but also potentially synergic. Small reports suggest that drugs preventing HF in the general population may be effective also among survivors of anticancer treatments, so that CV risk factors and disease, and chronic inflammation, may lead to indication to cardiac surgery in survivors of anticancer treatments. There is a lack of substantial data on whether current risk scores are efficient to predict prognosis after cardiac surgery in survivors of anticancer treatments, and to guide tailored decision-making. IHD is the most common condition requiring cardiac surgery among survivors of anticancer treatments. Primary VHD is mostly related to a history of radiation therapy. No specific reports exist on AoS in survivors of anticancer treatments. CONCLUSIONS: It is unclear whether interventions to dominate cancer- and anticancer treatment-related metabolic syndromes, chronic inflammation, and endothelial dysfunction, leading to IHD, nonIHD, VHD, HF, and AoS, are as effective in survivors of anticancer treatments as in the general population. When CV diseases require cardiac surgery, survivors of anticancer treatments may be a population at specifically elevated risk, rather than affected by a specific risk factor.

Big Data in cardiac surgery: real world and perspectives.

Big Data, and the derived analysis techniques, such as artificial intelligence and machine learning, have been considered a revolution in the modern practice of medicine. Big Data comes from multiple sources, encompassing electronic health records, clinical studies, imaging data, registries, administrative databases, patient-reported outcomes and OMICS profiles. The main objective of such analyses is to unveil hidden associations and patterns. In cardiac surgery, the main targets for the use of Big Data are the construction of predictive models to recognize patterns or associations better representing the individual risk or prognosis compared to classical surgical risk scores. The results of these studies contributed to kindle the interest for personalized medicine and contributed to recognize the limitations of randomized controlled trials in representing the real world. However, the main sources of evidence for guidelines and recommendations remain RCTs and meta-analysis. The extent of the revolution of Big Data and new analytical models in cardiac surgery is yet to be determined.

Right and left ventricular structures and functions in acute HFpEF: comparing the hypertensive pulmonary edema and worsening heart failure phenotypes.

BACKGROUND: Limited data are available on right (RV) and left (LV) ventricular structures and functions in acute heart failure with preserved ejection fraction (AHF-pEF) presenting with hypertensive pulmonary edema (APE) versus predominant peripheral edema (peHF). METHODS AND RESULTS: In a prospective study of consecutive patients with AHF-pEF, 80 patients met inclusion and not exclusion criteria, and underwent echocardiographic and laboratory examination in the emergency ward. The survived (94%) were re-evaluated at the discharge. At admission, systolic, diastolic, pulse blood pressure (BP), and high sensitivity troponin I were higher (all P < 0.05) with APE than with peHF while brain-type natriuretic peptide (BNP), hemoglobin and estimated glomerular filtration rate (eGFR) did not differ between the two phenotypes. LV volumes and EF were comparable between APE and peHF, but APE showed lower relative wall thickness (RWT), smaller left atrial (LA) volume, higher pulse pressure/stroke volume (PP/SV), and higher ratio between the peak velocities of the early diastolic waves sampled by traditional and tissue Doppler modality (mitral E/e', all P < 0.05). Right ventricular and atrial (RA) areas were smaller, tricuspid anular plane systolic excursion (TAPSE) and estimated pulmonary artery peak systolic pressure (sPAP) were higher with APE than with peHF (all P < 0.05) while averaged degree of severity of tricuspid insufficiency was greater with peHF than with APE. At discharge, PP/SV, mitral E/e', sPAP, RV sizes were reduced from admission in both phenotypes (all P < 0.05) and did not differ anymore between phenotypes, whereas LV EF and TAPSE did not show significant changes over time and treatments. CONCLUSION: In AHF-pEF, at comparable BNP and LV EF, hypertensive APE showed eccentric LV geometry but smaller RV and RA sizes, and higher RV systolic function, increased LV ventricular filling and systemic arterial loads. AHF resolution abolished the differences in PP/SV and LV diastolic load between APE and peHF whereas APE remained associated with more eccentric RV and higher TAPSE.

Predicting major events in ambulatory patients with advanced heart failure awaiting heart transplantation: a pilot study.

AIMS: In heart failure (HF), prognostic risk scores focus on all-cause mortality prediction. However, in advanced HF (AdHF) ambulatory patients awaiting heart transplantation (HTx), hospitalizations for acutely decompensated/worsening HF are relevant to clinical decision-making, but unpredicted by common risk functions. METHODS: Among consecutive ambulatory patients added to the waitlist for HTx, event discriminators within 2 years from recruitment were assessed prospectively by area under the curve from receiver-operating characteristic curves, and by Cox proportional hazards models. Primary composite end points included the first between all-cause mortality and acutely decompensated/worsening HF requiring hospitalization and specific treatments. RESULTS: In 89 patients, 36 primary composite events were recorded in a 2-year follow-up (40% of the study sample), and associated with nonischemic etiology and nonsinus rhythm, with lower systolic blood pressure (BP), lower plasma sodium and hemoglobin concentrations, and with higher N-terminal pro-brain natriuretic peptide (NT-proBNP), larger left ventricular (LV) dimensions and lower LV ejection fraction, greater proportion of significant mitral regurgitation, lower tricuspid annulus peak systolic excursion (TAPSE), lower percentage of predicted distance at 6-minute walking test (%p6MWT) and lower global symptoms burden by the Kansas City Cardiomyopathy Questionnaire, lower peak oxygen uptake by cardiopulmonary exercise, and higher wedge pressure by right heart catheterization, as compared with those with no events (P < 0.05). Only Metabolic Exercise Cardiac Kidney Index (MECKI) at recruitment was higher with patients reporting events, which predicted composite end points in addition to and independently of NT-proBNP, and lower systolic BP (all P < 0.05). In an alternative risk model, severe mitral regurgitation and lower TAPSE replaced MECKI and BP but not NT-proBNP (all P < 0.01). CONCLUSION: Higher NT-pro-BNP, lower systolic BP and higher MECKI may contribute to predicting all-cause death and acutely decompensated/worsening HF among ambulatory patients awaiting HTx, with lower TAPSE and severe mitral regurgitation representing further alternative independent prognosticators.

[ANMCO Position paper: Care pathway for advanced heart failure patients candidate for heart transplantation/ventricular assist device]. / Position paper ANMCO: Percorso assistenziale del paziente con insufficienza cardiaca avanzata candidabile a trapianto/assistenza ventricolare meccanica.

Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.

Comparison of Troponin I levels versus myocardial dysfunction on prognosis in sepsis.

In the context of sepsis, we tested the relationship between echocardiographic findings and Troponin, and their impact on prognosis. In this prospective study, we enrolled 325 septic patients (41% with shock), not mechanically ventilated, between October, 2012 and June, 2019 among those admitted to our High-Dependency Unit. By echocardiography within 24 h from the admission, sepsis-induced myocardial dysfunction (SIMD) was defined as left ventricular (LV) systolic dysfunction (speckle-tracking-based global longitudinal peak systolic strain, GLS, > - 14%) and/or right ventricular (RV) systolic dysfunction (Tricuspid Annular Plane Systolic Excursion, TAPSE < 16 mm). Troponin I levels were measured upon admission (T0) and after 24 h (T1); it was considered normal if > 0.1 ng/mL. Mortality was assessed at day-7 and day-28 end-points. One-hundred and forty-two patients had normal Troponin level at T0 and T1 (G1), 69 had abnormal levels at T0 or T1 (G2) and 114 showed abnormal Troponin levels at both T0 and T1 (G3). Compared to G1, patients in G3 had worse LV and RV systolic function (GLS - 11.6 ± 3.4% vs - 14.0 ± 3.5%, p < 0.001; TAPSE 18 ± 0.5 vs 19 ± 0.5 mm, p = 0.047) and greater day-28 (34% vs 20%, p = 0.015) mortality. In a Cox survival analysis including age, Troponin and SOFA score, mortality was predicted by the presence of SIMD (RR 3.24, 95% CI 1.72-6.11, p < 0.001) with no contribution of abnormal Troponin level. While abnormal Troponin levels were associated with SIMD diagnosed by echocardiography, only the presence of SIMD predicted the short- and medium-term mortality rate, without an independent contribution of increased Troponin levels.

Epidemiology of cardiomyopathies: essential context knowledge for a tailored clinical work-up.

Cardiomyopathies (CMPs) are primary disorders of myocardial structure and function in the absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease. Knowledge of the incidence and prevalence of CMPs may help clinicians to compare their observations in clinical practice with expected cases per person-year and to avoid under-reporting in clinical context. Currently, available estimates of prevalence and incidence of CMPs are based on clinical data, collected with a wide variability in population-source, and before the genetic testing evolved as a standard diagnostic tool. This review focuses on the epidemiology of CMPs in subjects aged between 18 and 55 years. A structured up-to-date diagnostic flow-chart for CMPs diagnosis and assessment is proposed to avoid misdiagnosis of CMPs in the young population and in subjects with unexplained cardiac disorders.

Machine Learning and Bioinformatics Framework Integration to Potential Familial DCM-Related Markers Discovery.

OBJECTIVES: Dilated cardiomyopathy (DCM) is characterized by a specific transcriptome. Since the DCM molecular network is largely unknown, the aim was to identify specific disease-related molecular targets combining an original machine learning (ML) approach with protein-protein interaction network. METHODS: The transcriptomic profiles of human myocardial tissues were investigated integrating an original computational approach, based on the Custom Decision Tree algorithm, in a differential expression bioinformatic framework. Validation was performed by quantitative real-time PCR. RESULTS: Our preliminary study, using samples from transplanted tissues, allowed the discovery of specific DCM-related genes, including MYH6, NPPA, MT-RNR1 and NEAT1, already known to be involved in cardiomyopathies Interestingly, a combination of these expression profiles with clinical characteristics showed a significant association between NEAT1 and left ventricular end-diastolic diameter (LVEDD) (Rho = 0.73, p = 0.05), according to severity classification (NYHA-class III). CONCLUSIONS: The use of the ML approach was useful to discover preliminary specific genes that could lead to a rapid selection of molecular targets correlated with DCM clinical parameters. For the first time, NEAT1 under-expression was significantly associated with LVEDD in the human heart.

Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs.

Cancer immunotherapy significantly contributed to an improvement in the prognosis of cancer patients. Immunotherapy, including human epidermal growth factor receptor 2 (HER2)-targeted therapies, immune checkpoint inhibitors (ICI), and chimeric antigen receptor-modified T (CAR-T), share the characteristic to exploit the capabilities of the immune system to kill cancerous cells. Trastuzumab is a monoclonal antibody against HER2 that prevents HER2-mediated signaling; it is administered mainly in HER2-positive cancers, such as breast, colorectal, biliary tract, and non-small-cell lung cancers. Immune checkpoint inhibitors (ICI) inhibit the binding of CTLA-4 or PD-1 to PDL-1, allowing T cells to kill cancerous cells. ICI can be used in melanomas, non-small-cell lung cancer, urothelial, and head and neck cancer. There are two main types of T-cell transfer therapy: tumor-infiltrating lymphocytes (or TIL) therapy and chimeric antigen receptor-modified T (CAR-T) cell therapy, mainly applied for B-cell lymphoma and leukemia and mantle-cell lymphoma. HER2-targeted therapies, mainly trastuzumab, are associated with left ventricular dysfunction, usually reversible and rarely life-threatening. PD/PDL-1 inhibitors can cause myocarditis, rare but potentially fulminant and associated with a high fatality rate. CAR-T therapy is associated with several cardiac toxic effects, mainly in the context of a systemic adverse effect, the cytokines release syndrome.

Severe Cardiac Toxicity Induced by Cancer Therapies Requiring Intensive Care Unit Admission.

A steadying increase of cancer survivors has been observed as a consequence of more effective therapies. However, chemotherapy regimens are often associated with significant toxicity, and cardiac damage emerges as a prominent clinical issue. Many mechanisms sustain chemotherapy-induced cardiac toxicity: direct myocyte damage, arrhythmia induction, coronary vasospasm, and accelerated atherosclerosis. Anthracyclines are the most studied cardiotoxic drugs and represent a clinical model for cardiac damage induced by chemotherapy. In patients suffering from advanced heart failure (HF) because of chemotherapy-related cardiomyopathy, when refractory to optimal medical therapy, mechanical circulatory support or heart transplantation represents an effective treatment. Here, the main mechanisms of cardiac toxicity induced by cancer therapies are analyzed, with a focus on patients requiring intensive care unit (ICU) admission during the course of the disease because of acute cardiac toxicity, takotsubo syndrome, and acute-on-chronic HF in patients suffering from chemotherapy-induced cardiomyopathy. In a subset of patients, cardiac toxicity can be acute and life-threatening, leading to overt cardiogenic shock. The management of critically ill cancer patients poses a unique challenge and requires a multidisciplinary approach. Moreover, no etiologic therapy is available, and only supportive measures can be implemented.

Epigenetic Therapies for Heart Failure: Current Insights and Future Potential.

Despite the current reductionist approach providing an optimal indication for diagnosis and treatment of patients with heart failure with reduced ejection fraction (HFrEF), there are no standard pharmacological therapies for heart failure with preserved ejection fraction (HFpEF). Although in its infancy in cardiovascular diseases, the epigenetic-based therapy ("epidrugs") is capturing the interest of physician community. In fact, an increasing number of controlled clinical trials is evaluating the putative beneficial effects of: 1) direct epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a possible indirect epigenetic interference, eg, metformin, statins, sodium glucose transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial has reported a reduction in first HF hospitalization (any EF value) and cardiovascular death in patients with type 2 diabetes and recent acute coronary syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF seem to benefit from supplementation to the standard therapy with statins, metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, the vasodilator hydralazine, with or without isosorbide dinitrate, did not provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk of incident HF and mortality in affected patients whereas clinical trials based on statins provided mixed results. Furthermore, PUFAs diet supplementation was significantly associated with reduced cardiovascular risk in both HFpEF and HFrEF. Future large trials will reveal whether direct and indirect epitherapy will remain a work in progress or become a useful way to customize the therapy in the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent advancement in the epitherapy as a possible way to improve personalized therapy of HF.

Novel biomarkers useful in surveillance of graft rejection after heart transplantation.

Heart transplantation (HTx) is considered the gold-standard therapy for the treatment of advanced heart failure (HF). The long-term survival in HTx is hindered by graft failure which represents one of the major limitations of the long-term efficacy of HTx. Endomyocardial biopsy (EMB) and the evaluation of donor-specific antibodies (DSA) are currently considered the essential diagnostic tools for surveillance of graft rejection. Recently, new molecular biomarkers (including cell-free DeoxyriboNucleic Acid, exosomes, gene profiling microarray, nanostring, reverse transcriptase multiplex ligation-dependent probe amplification, proteomics and immune profiling by quantitative multiplex immunofluorescence) provide useful information on mechanisms of graft rejection. The ambitious role of a similar change of perspective is aimed at a better and longer graft preservation.

[Cardiology units and organizational models of heart transplantation centers in Italy: a survey by the Italian Association of Hospital Cardiologists-Italian Society of Organ Transplantation (ANMCO-SITO)]. / Cardiologie e modelli organizzativi dei centri trapianto di cuore: indagine ANMCO-SITO.

BACKGROUND: The extent and quality of the involvement of cardiology units in health programs delivered by Italian centers for heart transplantation (HTx) have not been investigated previously. METHODS: The Italian Association of Hospital Cardiologists (ANMCO) and the Italian Society for Organ Transplantation (SITO) developed and delivered a nationwide survey to the Directors of the Italian centers for HTx to investigate the extent to which cardiology units contribute to HTx programs. The survey investigated: (i) the organization of the centers and institutional frame under which cardiology units contributed to HTx programs; (ii) the volumes of procedures and clinical services delivered by cardiology units to HTx centers for listing patients, following those waiting for HTx, managing acute heart failure, selecting and allocating organs to recipients, following and managing organ rejection after HTx. RESULTS: Of the 14 Italian centers involved, 13 provided full responses to the survey. Between 2017-2019, on average, 46% of the respondents performed up to 15 HTx/year, and additional 46% performed between 16 and 30 HTx/year. Of the respondents, 62% were included in a department of cardiac Surgery which did not include a cardiology unit; furthermore, 54% declared not to be included in a formal network for heart failure management. Cardiology units were the source for referrals of candidates to HTx in 85% cases. Of the respondents, 15% declared to be able to provide cardiological services thorough intra-center multidisciplinary team including cardiologists, whereas cardiological services were outsourced in 61% of the respondents. The clinical follow-up of patients waiting for HTx was performed directly by surgeons in 38% of the respondents. Worsening heart failure was managed directly by the HTx center in 33% of the cases using dedicated beds. Post-HTx follow-up, including endomyocardial biopsy, involved external cardiology units in less than 25% of the centers. CONCLUSIONS: The ANMCO-SITO survey shows that in Italy a very wide variability exists in terms of organization of HTx centers and their relationships with cardiology units for delivering specific cardiological services and procedures. In large majority, patient referral to HTx centers is mediated by cardiology units, whereas HTx was rarely included in a structured cardiological network for heart failure management.

Prognostic stratification in septic patients with overt and cryptic shock by speckle tracking echocardiography.

We evaluated the prevalence and prognostic value of left (LV) and right (RV) ventricular systolic dysfunction in the presence of overt and cryptic shock. In this prospective study, between October 2012 and June 2019, we enrolled 354 patients with sepsis, 41% with shock, among those admitted to the Emergency Department High-Dependency Unit. Patients were grouped based on the presence of shock, or by the presence of lactate levels ≥ (LAC +) or < 2 mmol/L (LAC-) evaluated within the first 24 h. By echocardiography performed within 24 h from the admission, LV systolic dysfunction was defined as global longitudinal strain (GLS) > -14%; RV systolic dysfunction as Tricuspid Annular Plane Systolic Excursion (TAPSE) < 16 mm. All-cause mortality was assessed at day-7 and day-28 follow-up. Mean values of LV GLS (-12.3 ± 3.4 vs -12.9 ± 3.8%) and TAPSE (1.8 ± 0.7 vs 1.8 ± 0.5 cm, all p = NS) were similar in patients with and in those without shock. LV GLS was significantly worse in LAC + than LAC- patients (- 11.2 ± 3.1 vs - 12.9 ± 3.7%, p = 0.001). In patients without shock, as well as in those LAC-, LV dysfunction was associated with increased day-28 mortality rate (78% vs 57% in non-survivors and survivors without shock and 74% vs 53% in non-survivors and survivors LAC-, all p < 0.01). LV (RR 2.26, 95% CI 1.37-3.74) and RV systolic dysfunction (RR 1.85, 95% CI 1.22-2.81) were associated with increased 28-day mortality rate in addition and independent to LAC + (RR 1.81, 95% CI 1.15-2.84). In conclusion, LV and RV ventricular dysfunction were independently associated with an increased mortality rate, altogether with the presence of cryptic shock.

Would You Prescribe Mobile Health Apps for Heart Failure Self-care? An Integrated Review of Commercially Available Mobile Technology for Heart Failure Patients.

Treatment of chronic diseases, such as heart failure, requires complex protocols based on early diagnosis; self-monitoring of symptoms, vital signs and physical activity; regular medication intake; and education of patients and caregivers about relevant aspects of the disease. Smartphones and mobile health applications could be very helpful in improving the efficacy of such protocols, but several barriers make it difficult to fully exploit their technological potential and produce clear clinical evidence of their effectiveness. App suppliers do not help users distinguish between useless/dangerous apps and valid solutions. The latter are few and often characterised by rapid obsolescence, lack of interactivity and lack of authoritative information. Systematic reviews can help physicians and researchers find and assess the 'best candidate solutions' in a repeatable manner and pave the way for well-grounded and fruitful discussion on their clinical effectiveness. To this purpose, the authors assess 10 apps for heart failure self-care using the Intercontinental Marketing Statistics score and other criteria, discuss the clinical effectiveness of existing solutions and identify barriers to their use in practice and drivers for change.