Association of a device-based remote management heart failure pathway with outcomes: TriageHF Plus real-world evaluation.

AIMS: Clinical pathways have been shown to improve outcomes in patients with heart failure (HF). Although patients with HF often have a cardiac implantable electronic device, few studies have reported the utility of device-derived risk scores to augment and organize care. TriageHF Plus is a device-based HF clinical pathway (DHFP) that uses remote monitoring alerts to trigger structured telephone assessment for HF stability and optimization. We aimed to evaluate the impact of TriageHF Plus on hospitalizations and describe the associated workforce burden. METHODS AND RESULTS: TriageHF Plus was a multi-site, prospective study that compared outcomes for patients recruited between April 2019 and February 2021. All alert-triggered assessments were analysed to determine the appropriateness of the alert and the workload burden. A negative-binomial regression with inverse probability treatment weighting using a time-matched usual care cohort was applied to estimate the effect of TriageHF Plus on non-elective hospitalizations. A post hoc pre-COVID-19 sensitivity analysis was also performed. The TriageHF Plus cohort (n = 443) had a mean age of 68.8 ± 11.2 years, 77% male (usual care cohort: n = 315, mean age of 66.2 ± 14.5 years, 65% male). In the TriageHF Plus cohort, an acute medical issue was identified following an alert in 79/182 (43%) cases. Fifty assessments indicated acute HF, requiring clinical action in 44 cases. At 30 day follow-up, 39/66 (59%) of initially symptomatic patients reported improvement, and 20 (19%) initially asymptomatic patients had developed new symptoms. On average, each assessment took 10 min. The TriageHF Plus group had a 58% lower rate of hospitalizations across full follow-up [incidence relative ratio: 0.42, 95% confidence interval (CI): 0.23-0.76, P = 0.004]. Across the pre-COVID-19 window, hospitalizations were 31% lower (0.69, 95% CI: 0.46-1.04, P = 0.077). CONCLUSIONS: These data represent the largest real-world evaluation of a DHFP based on multi-parametric risk stratification. The TriageHF Plus clinical pathway was associated with an improvement in HF symptoms and reduced all-cause hospitalizations.

Multispecialty multidisciplinary input into comorbidities along with treatment optimisation in heart failure reduces hospitalisation and clinic attendance.

AIMS: Heart failure (HF) is associated with comorbidities which independently influence treatment response and outcomes. This retrospective observational study (January 2020-June 2021) analysed the impact of monthly HF multispecialty multidisciplinary team (MDT) meetings to address management of HF comorbidities and thereby on provision, cost of care and HF outcomes. METHODS: Patients acted as their own controls, with outcomes compared for equal periods (for each patient) pre (HF MDT) versus post-MDT (multispecialty) meeting. The multispecialty MDT comprised HF cardiologists (primary, secondary, tertiary care), HF nurses, nephrologist, endocrinologist, palliative care, chest physician, pharmacist, clinical pharmacologist and geriatrician. Outcome measures were (1) all-cause hospitalisations, (2) outpatient clinic attendances and (3) cost. RESULTS: 334 patients (mean age 72.5±11 years) were discussed virtually through MDT meetings and follow-up duration was 13.9±4 months. Mean age-adjusted Charlson Comorbidity Index was 7.6±2.1 and Rockwood Frailty Score 5.5±1.6. Multispecialty interventions included optimising diabetes therapy (haemoglobin A1c-HbA1c pre-MDT 68±11 mmol/mol vs post-MDT 61±9 mmol/mol; p<0.001), deprescribing to reduce anticholinergic burden (pre-MDT 1.85±0.4 vs 1.5±0.3 post-MDT; p<0.001), initiation of renin-angiotensin aldosterone system inhibitors in HF with reduced ejection fraction (HFrEF) with advanced chronic kidney disease (9% pre vs 71% post-MDT; p<0.001). Other interventions included potassium binders, treatment of anaemia, falls assessment, management of chest conditions, day-case ascitic, pleural drains and palliative support. Total cost of funding monthly multispecialty meetings was £32 400 and resultant 64 clinic appointments cost £9600. The post-MDT study period was associated with reduction in 481 clinic appointments (cost saving £72150) and reduced all-cause hospitalisations (pre-MDT 1.1±0.4 vs 0.6±0.1 post-MDT; p<0.001), reduction of 1586 hospital bed-days and cost savings of £634 400. Total cost saving to the healthcare system was £664 550. CONCLUSION: HF multispecialty virtual MDT model provides integrated, holistic care across all healthcare tiers for management of HF and associated comorbidities. This approach is associated with reduced clinic attendances and all-cause hospitalisations, leading to significant cost savings.

A comparison of medical therapy and ablation for atrial fibrillation in patients with heart failure.

INTRODUCTION: Atrial fibrillation and heart failure frequently co-exist and the combination is associated with a worse prognosis than either condition alone. A number of pharmacological agents and invasive procedures have been shown to benefit this complex patient group. OBJECTIVE: In this review, we compare different therapeutic approaches to atrial fibrillation and heart failure, including pharmacotherapy, left atrial catheter ablation and pace-and-ablate. EXPERT OPINION: Left atrial catheter ablation is an efficacious option for restoring sinus rhythm and is most likely to provide benefit to those in whom durable sinus rhythm can be expected, and whose life expectancy is not significantly reduced by other pathologies or advanced age. A pace-and-ablate approach, particularly with physiological pacing, may provide more benefit to those with low chance of maintaining sinus rhythm. Both invasive options generally outperform pharmacotherapy, although it is important to individualize the approach for each patient through shared decision-making.

Use of CIED Generated Heart Failure Risk Score (HFRS) Alerts in an Integrated, Multi-Disciplinary Approach to HF Management-A Prospective Cohort Study.

Aim: To evaluate use of CIED-generated Heart Failure Risk Score (HFRS) alerts in an integrated, multi-disciplinary approach to HF management. Methods: We undertook a prospective, single centre outcome study of patients implanted with an HFRS-enabled Medtronic CIED, generating a "high risk" alert between November 2018 and November 2020. All patients generating a "high risk" HFRS alert were managed within an integrated HF pathway. Alerts were shared with local HF teams, prompting patient contact and appropriate intervention. Outcome data on health care utilisation (HCU) and mortality were collected. A validated questionnaire was completed by the HF teams to obtain feedback. Results: 367 "High risk" alerts were noted in 188 patients. The mean patient age was 70 and 49% had a Charlson Comorbidity Score of >6. Mean number of alerts per patients was 1.95 and 44 (23%) of patients had >3 "high risk" alerts in the follow up period. Overall, 75 (39%) patients were hospitalised in the 4−6-week period of the alert; 53 (28%) were unplanned of which 24 (13%) were for decompensated HF. A total of 33 (18%) patients died in the study period. Having three or more alerts significantly increased the risk of hospitalisation for heart failure (HR 2.5, CI 1.1−5.6 p = 0.03). The feedback on the pathway was positive. Conclusions: Patients with "high risk" alerts are co-morbid and have significant HCU. An integrated approach can facilitate timely risk stratification and intervention. Intervention in these patients is not limited to HF alone and provides the opportunity for holistic management of this complex cohort.

Clean air as an experience good in urban China.

The surprise economic shutdown due to COVID-19 caused a sharp improvement in urban air quality in many previously heavily polluted Chinese cities. If clean air is a valued experience good, then this short-term reduction in pollution in spring 2020 could have persistent medium-term effects on reducing urban pollution levels as cities adopt new "blue sky" regulations to maintain recent pollution progress. We document that China's cross-city Environmental Kuznets Curve shifts as a function of a city's demand for clean air. We rank 144 cities in China based on their population's baseline sensitivity to air pollution and with respect to their recent air pollution gains due to the COVID shutdown. The largest experience good effect should take place for cities featuring a high pollution sensitive population and where air quality has sharply improved during the pandemic. The residents of these cities have increased their online discussions focused on environmental protection, and local officials are incorporating "green" industrial subsidies into post-COVID stimulus policies.

Primary care heart failure service identifies a missed cohort of heart failure patients with reduced ejection fraction.

AIMS: We explored whether a missed cohort of patients in the community with heart failure (HF) and left ventricular systolic dysfunction (LVSD) could be identified and receive treatment optimization through a primary care heart failure (PCHF) service. METHODS AND RESULTS: PCHF is a partnership between Inspira Health, National Health Service Cardiologists and Medtronic. The PCHF service uses retrospective clinical audit to identify patients requiring a prospective face-to-face consultation with a consultant cardiologist for clinical review of their HF management within primary care. The service is delivered via five phases: (i) system interrogation of general practitioner (GP) systems; (ii) clinical audit of medical records; (iii) patient invitation; (iv) consultant reviews; and (v) follow-up. A total of 78 GP practices (864 194 population) have participated. In total, 19 393 patients' records were audited. HF register was 9668 (prevalence 1.1%) with 6162 patients coded with LVSD (prevalence 0.7%). HF case finder identified 9725 additional patients to be audited of whom 2916 patients required LVSD codes adding to the patient medical record (47% increase in LVSD). Prevalence of HF with LVSD increased from 0.7% to 1.05%. A total of 662 patients were invited for consultant cardiologist review at their local GP practice. The service found that within primary care, 27% of HF patients identified for a cardiologist consultation were eligible for complex device therapy, 45% required medicines optimization, and 47% of patients audited required diagnosis codes adding to their GP record. CONCLUSION: A PCHF service can identify a missed cohort of patients with HF and LVSD, enabling the optimization of prognostic medication and an increase in device prescription.

Immunotherapy for Metastatic Prostate Cancer: Current and Emerging Treatment Options.

The advent of immunotherapy has revolutionized cancer treatment. Prostate cancer has an immunosuppressive microenvironment and a low tumor mutation burden, resulting in low neoantigen expression. The consensus was that immunotherapy would be less effective in prostate cancer. However, recent studies have reported that prostate cancer does have a high number of DNA damage and repair gene defects. Immunotherapies that have been tested in prostate cancer so far have been mainly vaccines and checkpoint inhibitors. A combination of genomically targeted therapies, with approaches to alleviate immune response and thereby make the tumor microenvironment immunologically hot, is promising.

Protecting the most vulnerable during COVID-19 and beyond: a case report on the remote management of heart failure patients with cardiac implantable electronic devices.

BACKGROUND: Heart failure (HF) patients with cardiac implantable electronic devices (CIEDs) represent an important cohort. They are at increased risk of hospitalization and mortality. We outline how remote-only management strategies, which leverage transmitted health-related data, can be used to optimize care for HF patients with a CIED during the COVID-19 pandemic. CASE SUMMARY: An 82-year-old man with HF, stable on medical therapy, underwent cardiac resynchronization therapy implantation in 2016. Modern CIEDs facilitate remote monitoring by providing real-time physiological data (thoracic impedance, heart rate and rhythm, etc.). The 'Triage Heart Failure Risk Score' (Triage-HFRS), available on Medtronic CIEDs, integrates several monitored physiological parameters into a risk prediction model classifying patients as low, medium, or high risk of HF events within 30 days. In November 2019, the patient was enrolled in an innovative clinical pathway (Triage-HF Plus) whereby any 'high' Triage-HF risk status transmission prompts a phone call-based virtual consultation. A high-risk alert was received via remote transmission on 11 March, triggering a phone call assessment. Upon reporting increasing breathlessness, diuretics were initiated. The prescription was remotely issued and delivered to the patient's home. This approach circumvented the need for all face-to-face reviews, delivering care in an entirely remote manner. DISCUSSION: The challenges posed by COVID-19 have prompted us to think differently about how we deliver care for patients, both now and following the pandemic. Contemporary CIEDs facilitate the ability to remotely monitor HF patients by providing rich physiological data that can help identify individuals at elevated risk of decompensation using automated device-generated alerts.

Air pollution lowers Chinese urbanites' expressed happiness on social media.

High levels of air pollution in China may contribute to the urban population's reported low level of happiness1-3. To test this claim, we have constructed a daily city-level expressed happiness metric based on the sentiment in the contents of 210 million geotagged tweets on the Chinese largest microblog platform Sina Weibo4-6, and studied its dynamics relative to daily local air quality index and PM2.5 concentrations (fine particulate matter with diameters equal or smaller than 2.5 µm, the most prominent air pollutant in Chinese cities). Using daily data for 144 Chinese cities in 2014, we document that, on average, a one standard deviation increase in the PM2.5 concentration (or Air Quality Index) is associated with a 0.043 (or 0.046) standard deviation decrease in the happiness index. People suffer more on weekends, holidays and days with extreme weather conditions. The expressed happiness of women and the residents of both the cleanest and dirtiest cities are more sensitive to air pollution. Social media data provides real-time feedback for China's government about rising quality of life concerns.

Data set from the Union Army samples to study locational choice and social networks.

We describe the publicly available data created by the NIA funded Early Indicators program project, often referred to as the Union Army data, and the subset of these data used in "Persistent Social Networks: Civil War Veterans Who Fought Together Co-Locate in Later Life" (Costa et al., Forthcoming) [1]. This data subset can be used for reproducibility and extensions and also illustrates how the original complex data derived from archival administrative records can be used.

Persistent Social Networks: Civil War Veterans Who Fought Together Co-Locate in Later Life.

We demonstrate the long reach of early social ties in the location decision of individuals and in their older age mortality risk using data on Union Army veterans of the US Civil War (1861-5). We estimate discrete choice migration models to quantify the trade-offs across locations faced by veterans. Veterans were more likely to move to a neighborhood or county where men from their same war company lived and were more likely to move to such areas than to areas where other veterans were located. Veterans also were less likely to move far from their origin and avoided urban immigrant areas and high mortality risk areas. They also avoided areas that opposed the Civil War. This co-location evidence highlights the existence of persistent social networks. Such social networks had long-term consequences: veterans living close to war-time comrades had a 6% lower probability of dying.

DEATH AND THE MEDIA: INFECTIOUS DISEASE REPORTING DURING THE HEALTH TRANSITION.

In the late 19th Century, cities in Western Europe and the United States suffered from high levels of infectious disease. Over a 40 year period, there was a dramatic decline in infectious disease deaths in cities. As such objective progress in urban quality of life took place, how did the media report this trend? At that time newspapers were the major source of information educating urban households about the risks they faced. By constructing a unique panel data base, we find that news reports were positively associated with government announced typhoid mortality counts and the size of this effect actually grew after the local governments made large investments in public water works to reduce typhoid rates. News coverage was more responsive to unexpected increases in death rates than to unexpected decreases in death rates.

Optimal real estate capital durability and localized climate change disaster risk.

The durability of the real estate capital stock could hinder climate change adaptation because past construction anchors the population in beautiful and productive but increasingly-risky coastal areas. However, coastal developers anticipate that their assets face increasing risk and this creates an incentive to seek adaptation strategies. This paper models climate change as a joint process of (1) increasingly destructive storms and (2) a risk of sea-level rise that submerges coastal property. We study how forward-looking developers and real estate investors respond to the new risks along a number of dimensions including their choices of location, capital durability, capital mobility (modular real estate), and maintenance of existing properties. The net effect of such investments is a more resilient urban population.

Declining Mortality Inequality within Cities during the Health Transition.

In the United States in the late 19th and early 20th century, large cities had extremely high death rates from infectious disease. Within major cities such as New York City and Philadelphia, there was significant variation at any point in time in the mortality rate across neighborhoods. Between 1900 and 1930 neighborhood mortality convergence took place in New York City and Philadelphia. We document these trends and discuss their consequences for neighborhood quality of life dynamics and the economic incidence of who gains from effective public health interventions.

China's bullet trains facilitate market integration and mitigate the cost of megacity growth.

Megacity growth in the developing world is fueled by a desire to access their large local labor markets. Growing megacities suffer from high levels of traffic congestion and pollution, which degrade local quality of life. Transportation technology that allows individuals to access the megacity without living within its boundaries offers potentially large social benefits, because individuals can enjoy the benefits of urban agglomeration while not paying megacity real estate rents and suffering from the city's social costs. This paper presents evidence supporting the claim that China's bullet trains are playing this role. The bullet train is regarded as one of the most significant technological breakthroughs in passenger transportation developed in the second half of the 20th century. Starting in 2007, China has introduced several new bullet trains that connect megacities such as Beijing, Shanghai, and Guangzhou with nearby cities. Through facilitating market integration, bullet trains will stimulate the development of second- and third-tier cities. By offering households and firms a larger menu of location alternatives, bullet trains help to protect the quality of life of the growing urban population. We document that this transport innovation is associated with rising real estate prices in the nearby secondary cities.

Increasing circulating IGFBP1 levels improves insulin sensitivity, promotes nitric oxide production, lowers blood pressure, and protects against atherosclerosis.

Low concentrations of insulin-like growth factor (IGF) binding protein-1 (IGFBP1) are associated with insulin resistance, diabetes, and cardiovascular disease. We investigated whether increasing IGFBP1 levels can prevent the development of these disorders. Metabolic and vascular phenotype were examined in response to human IGFBP1 overexpression in mice with diet-induced obesity, mice heterozygous for deletion of insulin receptors (IR(+/-)), and ApoE(-/-) mice. Direct effects of human (h)IGFBP1 on nitric oxide (NO) generation and cellular signaling were studied in isolated vessels and in human endothelial cells. IGFBP1 circulating levels were markedly suppressed in dietary-induced obese mice. Overexpression of hIGFBP1 in obese mice reduced blood pressure, improved insulin sensitivity, and increased insulin-stimulated NO generation. In nonobese IR(+/-) mice, overexpression of hIGFBP1 reduced blood pressure and improved insulin-stimulated NO generation. hIGFBP1 induced vasodilatation independently of IGF and increased endothelial NO synthase (eNOS) activity in arterial segments ex vivo, while in endothelial cells, hIGFBP1 increased eNOS Ser(1177) phosphorylation via phosphatidylinositol 3-kinase signaling. Finally, in ApoE(-/-) mice, overexpression of hIGFBP1 reduced atherosclerosis. These favorable effects of hIGFBP1 on insulin sensitivity, blood pressure, NO production, and atherosclerosis suggest that increasing IGFBP1 concentration may be a novel approach to prevent cardiovascular disease in the setting of insulin resistance and diabetes.

Association of diabetes with increased all-cause mortality following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction in the contemporary era.

BACKGROUND: We investigated the association between diabetes mellitus (DM) and all-cause mortality in a large cohort of consecutive patients treated with primary percutaneous coronary intervention (PPCI) in the contemporary era. METHODS: We conducted a retrospective analysis of a single-centre registry of patients undergoing PPCI for ST-segment elevation myocardial infarction (STEMI) at a large regional PCI centre between 2005 and 2009. All-cause mortality in relation to patient and procedural characteristics was compared between patients with and without DM. RESULTS: Of 2586 patients undergoing PPCI, 310 (12%) had DM. Patients with DM had a higher prevalence of multi-vessel coronary disease (p<0.001) and prior myocardial infarction (p<0.001). Patients with DM were less commonly admitted directly to the interventional centre (p=0.002). Symptom-to-balloon (p<0.001) and door-to-balloon time (p=0.002) were longer in patients with DM. Final infarct-related-artery TIMI-flow grade was lower in patients with DM (p=0.031). All-cause mortality at 30 days (p=0.0025) and 1 year (p<0.0001) was higher in patients with DM. DM was independently associated with increased mortality after multivariate adjustment for potential confounders. CONCLUSIONS: Mortality remains substantially higher in patients with DM following reperfusion for STEMI in comparison with those without diabetes, despite contemporary management with PPCI. Greater co-morbidity, delayed presentation, longer times-to-reperfusion, and less optimal reperfusion may contribute to adverse outcomes.

The insulin-like growth factor-1 receptor is a negative regulator of nitric oxide bioavailability and insulin sensitivity in the endothelium.

OBJECTIVE: In mice, haploinsufficiency of the IGF-1 receptor (IGF-1R(+/-)), at a whole-body level, increases resistance to inflammation and oxidative stress, but the underlying mechanisms are unclear. We hypothesized that by forming insulin-resistant heterodimers composed of one IGF-1Rαß and one insulin receptor (IR), IRαß complex in endothelial cells (ECs), IGF-1R reduces free IR, which reduces EC insulin sensitivity and generation of the antioxidant/anti-inflammatory signaling radical nitric oxide (NO). RESEARCH DESIGN AND METHODS: Using a number of complementary gene-modified mice with reduced IGF-1R at a whole-body level and specifically in EC, and complementary studies in EC in vitro, we examined the effect of changing IGF-1R/IR stoichiometry on EC insulin sensitivity and NO bioavailability. RESULTS: IGF-1R(+/-) mice had enhanced insulin-mediated glucose lowering. Aortas from these mice were hypocontractile to phenylephrine (PE) and had increased basal NO generation and augmented insulin-mediated NO release from EC. To dissect EC from whole-body effects we generated mice with EC-specific knockdown of IGF-1R. Aortas from these mice were also hypocontractile to PE and had increased basal NO generation. Whole-body and EC deletion of IGF-1R reduced hybrid receptor formation. By reducing IGF-1R in IR-haploinsufficient mice we reduced hybrid formation, restored insulin-mediated vasorelaxation in aorta, and insulin stimulated NO release in EC. Complementary studies in human umbilical vein EC in which IGF-1R was reduced using siRNA confirmed that reducing IGF-1R has favorable effects on NO bioavailability and EC insulin sensitivity. CONCLUSIONS: These data demonstrate that IGF-1R is a critical negative regulator of insulin sensitivity and NO bioavailability in the endothelium.