Under-recognition of heart failure in patients with atrial fibrillation and the impact of gender: a UK population-based cohort study

Background: Patients with atrial fibrillation (AF) complicated by heart failure (HF) have a poor prognosis. We investigated whether long term loop-diuretic therapy in patients with AF and no known diagnosis of HF, as a potential surrogate marker of undiagnosed HF, is also associated with worse outcomes. Methods: Adults with incident AF were identified from UK primary and secondary care records between 2004 and 2016. Repeat prescriptions for loop diuretics, without a diagnosis of HF or documented non-cardiac indication, were classified as ‘isolated’ loop diuretic use. Results: Amongst 124,256 people with incident AF (median 76 years, 47% women), 22,001 (17.7%) had a diagnosis of HF, and 22,325 (18.0%) had isolated loop diuretic use. During 2.9 (LQ-UQ 1–6) years’ follow-up, 12,182 patients were diagnosed with HF (incidence rate 3.2 [95% CI 3.1–3.3]/100 person-years). Of these, 3999 (32.8%) had prior isolated loop diuretic use, including 31% of patients diagnosed with HF following an emergency hospitalisation. The median time from AF to HF diagnosis was 3.6 (1.2–7.7) years in men versus 5.1 (1.8–9.9) years in women (p = 0.0001). In adjusted models, patients with isolated loop diuretic use had higher mortality (HR 1.42 [95% CI 1.37–1.47], p < 0.0005) and risk of HF hospitalisation (HR 1.60 [95% CI 1.42–1.80], p < 0.0005) than patients with no HF or loop diuretic use, and comparably poor survival to patients with diagnosed HF. Conclusions: Loop diuretics are commonly prescribed to patients with AF and may indicate increased cardiovascular risk. Targeted evaluation of these patients may allow earlier HF diagnosis, timely intervention, and better outcomes, particularly amongst women with AF, in whom HF appears to be under-recognised and diagnosed later than in men

Disposable Patterned Electroceutical Dressing (PED-10) Is Safe for Treatment of Open Clinical Chronic Wounds

Objective: To evaluate if patterned electroceutical dressing (PED) is safe for human chronic wounds treatment as reported by wound care providers. Approach: This work reports a pilot feasibility study with the primary objective to determine physically observable effects of PED application on host tissue response from a safety evaluation point of view. For this pilot study, patients receiving a lower extremity amputation with at least one open wound on the part to be amputated were enrolled. Patients were identified through the Ohio State University Wexner Medical Center (OSUWMC) based on inclusion and exclusion criteria through prescreening through the Comprehensive Wound Center's (CWC) Limb Preservation Program and wound physicians and/or providers at OSUWMC. Wounds were treated with the PED before amputation surgery. Results: The intent of the study was to identify if PED was safe for clinical application based on visual observations of adverse or lack of adverse events on skin and wound tissue. The pilot testing performed on a small cohort (N = 8) of patients showed that with engineered voltage regulation of current flow to the open wound, the PED can be used with little to no visually observable adverse effects on chronic human skin wounds. Innovation: The PED was developed as a second-generation tunable electroceutical wound care dressing, which could potentially be used to treat wounds with deeper infections compared with current state of the art that treats wounds with treatment zone limited to the surface near topical application. Conclusion: Technology advances in design and fabrication of electroceutical dressings were leveraged to develop a tunable laboratory prototype that could be used as a disposable low-cost electroceutical wound care dressing on chronic wounds. Design revisions of PED-1 (1 kΩ ballast resistor) circumvented previously observed adverse effects on the skin in the vicinity of an open wound. PED-10 (including a 10 kΩ ballast resistor) was well tolerated in the small cohort of patients (N = 8) on whom it was tested, and the observations reported here warrant a larger study to determine the clinical impact on human wound healing and infection control

The Pulmonary Venous Ridge Length to Stratify Stroke Risk in Atrial Fibrillation

Purpose of Study: To evaluate the left superior pulmonary venous ridge length (RL) and the left atrial appendage fractal dimension (LAA FD) as predictors of cardioembolic ischemic stroke (CVA) and transient ischemic attack (TIA) in patients with atrial fibrillation (AF). Materials, Methods and Procedures: A multicenter, retrospective multicenter study was conducted on patients with AF who underwent cardiac CT prior to catheter ablation between 01/01/2010 and 12/31/2015. Patients were grouped by the presence or absence of prior CVA/TIA. Patients with mitral stenosis, prior mechanical aortic valve replacement, ascending aortic arch atheroma, highrisk patent foramen ovale, history of atrial septal repair or device, preexisting LAA thrombus or intra-cardiac tumor, or prior open-heart surgery were excluded. Further exclusion was performed for patients with sub-optimal or unavailable cardiac CT imaging by investigators blinded to clinical data. Blinded investigators obtained RL by measuring the distance between the left superior pulmonary venous ostium and the internal ostium of the left atrial appendage. LAA FD was calculated using semi-automated volume rendering and processing software (ImageJ, Bethesda, MD) [1] and LAA FD are presented as means (95% confidence interval) and were compared between groups using unpaired t-tests. Logistic regression analysis was used to construct receiver operating curves and to assess the abilities of RL and LAA FD to predict prior CVA/TIA. Results: 225 patients met inclusion criteria. Mean RL were 4.32 (3.80-4.93) and 5.20 (4.93-5.48) for patients with (n=24; mean age: 59.4; 70.8% male) and without (n=165; mean age: 59.3; 75.4% male) prior CVA/TIA, respectively(p=0.033). Mean LAA FD were 2.29 (95% CI: 2.24-2.34) and 2.33 (2.32-2.34) for patients with (n=22; mean age: 60.3; 68.2% male) and without (n=171; mean age: 59.3; 74.9% male) prior CVA/TIA, respectively (p=0.052). In a regression model including LAA FD, RL, and established predictive markers, only RL predicted prior CVA/TIA (OR 0.73; 0.54 to 0.98; p=0.034). Discussion: Lower RL values were associated with prior CVA/TIA, whereas LAA FD values were similar between patients with AF with and without prior CVA/TIA. RL is a novel marker that may refine clinical decision-making regarding anticoagulation goals and treatment decisions for patients with AF. Future studies with larger samples should investigate the clinical utility of RL to improve CVA/TIA risk stratification of patients with AF and prospectively reduce the incidence of CVA/TIA in this population

Validation of U.S. mortality prediction models for hospitalized heart failure in the United Kingdom and Japan: Validation of risk models in decompensated heart failure

Aims: Prognostic models for hospitalised heart failure (HHF) were developed predominantly for patients of European origin in the United States of America; it is unclear whether they perform similarly in other health-care systems or for different ethnicities. We sought to validate published prediction models for HHF in the United Kingdom (UK) & Japan.Methods and Results: Patients in the UK (894) and Japan (3,158) were prospectively enrolled and similar in terms of sex (~60% men) and median age (~77 years). Models predicted that British patients would have a higher mortality than Japanese, which was indeed true both for in-hospital [4.8% vs 2.5%] and 180-day [20.7% vs 9.5%] mortality. The model c-statistics for the published/derivation [range 0.70-0.76] and Japanese [range 0.75-0.77] cohorts were similar and higher than for the UK [0.62-0.75] but models consistently over-estimated mortality in Japan. For in-hospital mortality, OPTIMIZE-HF performed best, providing similar discrimination in published/derivation, UK and Japanese cohorts [c-indices: 0.75 (0.74-0.77); 0.75 (0.68 - 0.81) and 0.77 (0.70 - 0.83)], and least over-estimated mortality in Japan. For 180-day mortality, the cstatistics for ASCEND-HF were similar in published/derivation [0.70] and UK [0.69 (0.64 - 0.74)] cohorts but higher in Japan [0.75 (0.71 - 0.79)]; calibration was good in the UK but again over-estimated mortality in Japan.Conclusion: Calibration of published prediction models appear moderately accurate and unbiased when applied to British patients but consistently overestimate mortality in Japan. Identifying the reason why patients in Japan have a better than predicted prognosis is of great interest

Outcomes of surgical mitral and aortic valve replacements among kidney transplant candidates: implications for valve selection

Background: Limited literature exists that evaluated outcomes of kidney transplant–eligible patients who are having dialysis and who are undergoing valve replacement. Our main objective in this study was to compare mortality, reoperation, and bleeding episodes between bioprosthetic and mechanical valve procedures among kidney transplant–eligible patients who are having dialysis. Methods and Results: We studied 887 and 1925 dialysis patients from the United States Renal Data System, who underwent mitral valve replacement and aortic valve replacement (AVR) after being waitlisted for a kidney transplant (2000–2015), respectively. Time to death, time to reoperation, and time to bleeding requiring hospitalizations were compared separately for AVR and mitral valve replacement. Kaplan–Meier survival curves, Cox proportional hazards model for time to death, accelerated time to event model for time to reoperation, and counting process model for time to recurrent bleeding were used. There were no differences in mortality (hazard ratio [HR], 0.92; 95% CI, 0.77–1.09) or risk of reoperation or risk of significant bleeding events between bioprosthetic and mechanical mitral valve replacement. However, mechanical AVR was associated with a modestly significant less hazard of death (HR, 0.83; 95% CI, 0.74–0.94) compared with bioprosthetic AVR. There were no differences in time to reoperation, or time to significant bleeding events between bioprosthetic and mechanical AVR. Conclusions: For kidney transplant waitlisted patients who are on dialysis and who are undergoing surgical valve replacement, bioprosthetic and mechanical valves have comparable survival, reoperation rates, and bleeding episodes requiring hospitalizations at both mitral and aortic locations. These findings emphasize that an individualized informed decision is recommended when choosing the type of valve for this special group of patients having dialysis

Mortality after admission for heart failure in the UK compared with Japan

Objective Mortality amongst patients hospitalised for heart failure (HHF) in Western and Asian countries may differ, but this has not been investigated using individual patient-level data (IPLD). We sought to remedy this through rigorous statistical analysis of HHF registries and variable selection from a systematic literature review.Methods and results IPLD from registries of HHF in Japan (n=3781) and the UK (n=894) were obtained. A systematic literature review identified 23 models for predicting outcome of HHF. Five variables appearing in 10 or more reports were strongly related to prognosis (systolic blood pressure, serum sodium concentration, age, blood urea nitrogen and creatinine). To compare mortality in the UK and Japan, variables were imputed in a propensity model using inverse probability of treatment weighting (IPTW) and IPTW with logistic regression (doubly robust IPTW). Overall, patients in the UK were sicker and in-patient and post-discharge mortalities were greater, suggesting that the threshold for hospital admission was higher. Covariate-adjusted in-hospital mortality was similar in the UK and Japan (IPTW OR: 1.14, 95% CI 0.70 to 1.86), but 180-day postdischarge mortality was substantially higher in the UK (doubly robust IPTW OR: 2.33, 95% CI 1.58 to 3.43).Conclusions Despite robust methods to adjust for differences in patient characteristics and disease severity, HHF patients in the UK have roughly twice the mortality at 180 days compared with those in Japan. Similar analyses should be done using other data sets and in other countries to determine the consistency of these findings and identify factors that might inform healthcare policy and improve outcomes

Elena+ Care for COVID-19, A Pandemic Lifestyle Care Intervention: Intervention Design and Study Protocol

Background: The current COVID-19 coronavirus pandemic is an emergency on a global scale, with huge swathes of the population required to remain indoors for prolonged periods to tackle the virus. In this new context, individuals’ health-promoting routines are under greater strain, contributing to poorer mental and physical health. Additionally, individuals are required to keep up to date with latest health guidelines about the virus, which may be confusing in an age of social-media disinformation and shifting guidelines. To tackle these factors, we developed Elena+, a smartphone-based and conversational agent (CA) delivered pandemic lifestyle care intervention.Methods: Elena+ utilizes varied intervention components to deliver a psychoeducation-focused coaching program on the topics of: COVID-19 information, physical activity, mental health (anxiety, loneliness, mental resources), sleep and diet and nutrition. Over 43 subtopics, a CA guides individuals through content and tracks progress over time, such as changes in health outcome assessments per topic, alongside user-set behavioral intentions and user-reported actual behaviors. Ratings of the usage experience, social demographics and the user profile are also captured. Elena+ is available for public download on iOS and Android devices in English, European Spanish and Latin American Spanish with future languages and launch countries planned, and no limits on planned recruitment. Panel data methods will be used to track user progress over time in subsequent analyses. The Elena+ intervention is open-source under the Apache 2 license (MobileCoach software) and the Creative Commons 4.0 license CC BY-NC-SA (intervention logic and content), allowing future collaborations; such as cultural adaptions, integration of new sensor-related features or the development of new topics.Discussion: Digital health applications offer a low-cost and scalable route to meet challenges to public health. As Elena+ was developed by an international and interdisciplinary team in a short time frame to meet the COVID-19 pandemic, empirical data are required to discern how effective such solutions can be in meeting real world, emergent health crises. Additionally, clustering Elena+ users based on characteristics and usage behaviors could help public health practitioners understand how population-level digital health interventions can reach at-risk and sub-populations

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Epidemiology, healthcare resource utilisation, identification, and outcomes of different heart failure phenotypes in real world

While international guidelines for the management of heart failure (HF) largely overlap, important regional differences exist in patient characteristics, prescription patterns, healthcare resource utilisation and consequently, in clinical outcomes, between the Western and Asian countries. To date, comparative data on geographic differences in patient characteristics, management and outcomes has either been based on post-hoc analyses from clinical trials, aggregate patient data or from registries that lacked both quantum and generalisability. I therefore performed an individual patient-level analysis of more than one million non-consecutive heart failure hospitalisations across four countries – UK, US, Japan, and Taiwan – using nationally representative electronic health care records (EHR), which captured routine clinical encounters (Specific Aims 1 and 2). Although, multiple studies have been undertaken to efficiently identify patients with HF in the real world using EHR, there is a paucity of evidence on identification and validation of algorithms for identifying patients with specific HF phenotypes, including heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). As part of specific aim 3, I have focussed on improving the ability to identify patients with different HF phenotypes within the EHR, by collecting additional data (including direct questionnaire to General Practitioner’s), and by seeking to understand the impact of different algorithms for identification of HFrEF and HFpEF. HFpEF patients are widely believed to be a heterogenous and can be broadly categorised into two further sub-phenotypes at the population level: 1) young obese patients and 2) older non-obese patients where hypertension, chronic kidney disease, coronary artery disease (CAD) and atrial fibrillation are the predominant drivers. As part of specific aims 4 and 5, I have evaluated the obese HFpEF sub-phenotype and the impact of coronary revascularisation in patients with HFpEF (CAD-HFpEF sub-phenotype) using nationwide EHR.Open Acces

Survival analysis—part 3: intermediate events and the importance of competing risks

Learning objectives: 1. Understand what events can be labelled as intermediate events in survival analysis. 2. Understand why the Kaplan and Meier method cannot be used in the presence of competing events. 3. Regression analysis in the presence of competing events