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Abstract Aims Heart failure with reduced ejection fraction (HFrEF) is treatable but guideline‐directed medical therapy (GDMT) may not be affordable or accessible to people living with the disease. Methods and results In this cross‐sectional survey, we investigated the price, affordability, and accessibility of four pivotal classes of HFrEF GDMT: angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or angiotensin‐neprilysin inhibitors (ARNI); beta‐blockers; mineralocorticoid receptor antagonists (MRA); and sodium glucose co‐transporter 2 inhibitors (SGLT2i). We sampled online or community pharmacies in 10 countries across a range of World Bank income groups, assessing mean 30 day retail prescription prices, affordability relative to gross national income per capita per month, and accessibility. We reported median price ratios relative to the International Reference Standard. We performed a literature review to evaluate accessibility to GDMT classes through publicly funded drug programmes in each country. HFrEF GDMT prices, both absolute and relative to the international reference, were highest in the United States and lowest in Pakistan and Bangladesh. The most expensive drug was the ARNI, sacubitril/valsartan, with a mean (standard deviation, SD) 30 day price ranging from $11.06 (0.81) in Pakistan to $611.50 (3.54) in United States. The least expensive drug was the MRA, spironolactone, with a mean (SD) 30 day price ranging from $0.18 (0.00) in Pakistan to $12.32 (0.00) in England. Affordability (SD) of quadruple therapy—ARNI, beta‐blockers, MRA, and SGLT2i—was best in high‐income and worst in low‐income countries, ranging from 1.49 (0.00)% of gross national income per capita per month in England to 232.47 (31.47)% in Uganda. Publicly funded drug programmes offset costs for eligible patients, but ARNI and SGLT2i were inaccessible through these programmes in low‐ and middle‐income countries. Price, affordability, and access were substantially improved in all countries by substituting ARNI for ACEi/ARB. Conclusions There was marked variation between countries in the retail price of HFrEF GDMT. Despite higher prices in high‐income countries, GDMT was more accessible and affordable than in low‐ and middle‐income countries. Publicly funded drug programmes in lower income countries increased affordability but limited access to newer HFrEF GDMT classes. Pharmaco‐disparities must be addressed to improve HFrEF outcomes globally.

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by deficient activity of the enzyme alpha-galactosidase. While AFD is recognized as a progressive multi-system disorder, infiltrative cardiomyopathy causing a number of cardiovascular manifestations is recognized as an important complication of this disease. AFD affects both men and women, although the clinical presentation typically varies by sex, with men presenting at a younger age with more neurologic and renal phenotype and women developing a later onset variant with more cardiovascular manifestations. AFD is an important cause of increased myocardial wall thickness, and advances in imaging, in particular cardiac magnetic resonance imaging and T1 mapping techniques, have improved the ability to identify this disease non-invasively. Diagnosis is confirmed by the presence of low alpha-galactosidase activity and identification of a mutation in the GLA gene. Enzyme replacement therapy remains the mainstay of disease modifying therapy, with two formulations currently approved. In addition, newer treatments such as oral chaperone therapy are now available for select patients, with a number of other investigational therapies in development. The availability of these therapies has significantly improved outcomes for AFD patients. Improved survival and the availability of multiple agents has presented new clinical dilemmas regarding disease monitoring and surveillance using clinical, imaging and laboratory biomarkers, in addition to improved approaches to managing cardiovascular risk factors and AFD complications. This review will provide an update on clinical recognition and diagnostic approaches including differentiation from other causes of increased ventricular wall thickness, in addition to modern strategies for management and follow-up.

Abstract Background The LACE index—length of stay (L), acuity (A), Charlson co‐morbidities (C), and emergent visits (E)—predicts 30‐day outcomes following heart failure (HF) hospitalization but is complex to score. A simpler LE index (length of stay and emergent visits) could offer a practical advantage in point‐of‐care risk prediction. Methods and results This was a sub‐study of the patient‐centred care transitions in HF (PACT‐HF) multicentre trial. The derivation cohort comprised patients hospitalized for HF, enrolled in the trial, and followed prospectively. External validation was performed retrospectively in a cohort of patients hospitalized for HF. We used log‐binomial regression models with LACE or LE as the predictor and either 30‐day composite all‐cause readmission or death or 30‐day all‐cause readmission as the outcomes, adjusting only for post‐discharge services. There were 1985 patients (mean [SD] age 78.1 [12.1] years) in the derivation cohort and 378 (mean [SD] age 73.1 [13.2] years) in the validation cohort. Increments in the LACE and LE indices were associated with 17% (RR 1.17; 95% CI 1.12, 1.21; C‐statistic 0.64) and 21% (RR 1.21; 95% CI 1.15, 1.26; C‐statistic 0.63) increases, respectively, in 30‐day composite all‐cause readmission or death; and 16% (RR 1.16; 95% CI 1.11, 1.20; C‐statistic 0.64) and 18% (RR 1.18; 95% CI 1.13, 1.24; C‐statistic 0.62) increases, respectively, in 30‐day all‐cause readmission. The LE index provided better risk discrimination for the 30‐day outcomes than did the LACE index in the external validation cohort. Conclusions The LE index predicts 30‐day outcomes following HF hospitalization with similar or better performance than the more complex LACE index.

Abstract Aims The LE index (Length of hospitalization plus number of Emergent visits ≤6 months) predicts 30 day all‐cause readmission or death following hospitalization for heart failure (HF). We combined N‐terminal pro‐B type natriuretic peptide (NT‐proBNP) levels with the LE index to derive and validate the LENT index for risk prediction at the point of care on the day of hospital discharge. Methods and results In this prospective cohort sub‐study of the Patient‐centred Care Transitions in HF clinical trial, we used log‐binomial regression models with LE index and either admission or discharge NT‐proBNP as the predictors and 30 day composite all‐cause readmission or death as the primary outcome. No other variables were added to the model. We used regression coefficients to derive the LENT index and bootstrapping analysis for internal validation. There were 772 patients (mean [SD] age 77.0 [12.4] years, 49.9% female). Each increment in the LE index was associated with a 25% increased risk of the primary outcome (RR 1.25, 95% CI 1.16–1.35; C‐statistic 0.63). Adjusted for the LE index, every 10‐fold increase in admission and discharge NT‐proBNP was associated with a 48% (RR 1.48; 95% CI 1.10, 1.99; C‐statistic 0.64; net reclassification index [NRI] 0.19) and 56% (RR 1.56; 95% CI 1.08, 2.25; C‐statistic 0.64; NRI 0.21) increased risk of the primary outcome, respectively. The predicted probability of the primary outcome increased to a similar extent with incremental LENT, regardless of whether admission or discharge NT‐proBNP level was used. Conclusions The point‐of‐care LENT index predicts 30 day composite all‐cause readmission or death among patients hospitalized with HF, with improved risk reclassification compared with the LE index. The performance of this simple, 3‐variable index ‐ without adjustment for comorbidities ‐ is comparable to complex risk prediction models in HF. Trial Registration: ClinicalTrials.gov Identifier: NCT02112227

Background Patient‐reported outcomes (PROs) are important measures of treatment response in heart failure. We assessed temporal trends in and factors associated with inclusion of PROs in heart failure randomized controlled trials (RCTs). Methods and Results We searched MEDLINE, Embase, and CINAHL for studies published between January 2000 and July 2020 in journals with an impact factor ≥10. We assessed temporal trends using the Jonckheere‐Terpstra test and conducted multivariable logistic regression to explore trial characteristics associated with PRO inclusion. We assessed the quality of PRO reporting using the Consolidated Standards of Reporting Trials (CONSORT) PRO extension. Of 417 RCTs included, PROs were reported in 226 (54.2%; 95% CI, 49.3%–59.1%), with increased reporting between 2000 and 2020 (P

Purpose To characterise the dynamics and consequences of bullying in academic medical settings, report factors that promote academic bullying and describe potential interventions.Design Systematic review.Data sources We searched EMBASE and PsycINFO for articles published between 1 January 1999 and 7 February 2021.Study selection We included studies conducted in academic medical settings in which victims were consultants or trainees. Studies had to describe bullying behaviours; the perpetrators or victims; barriers or facilitators; impact or interventions. Data were assessed independently by two reviewers.Results We included 68 studies representing 82 349 respondents. Studies described academic bullying as the abuse of authority that impeded the education or career of the victim through punishing behaviours that included overwork, destabilisation and isolation in academic settings. Among 35 779 individuals who responded about bullying patterns in 28 studies, the most commonly described (38.2% respondents) was overwork. Among 24 894 individuals in 33 studies who reported the impact, the most common was psychological distress (39.1% respondents). Consultants were the most common bullies identified (53.6% of 15 868 respondents in 31 studies). Among demographic groups, men were identified as the most common perpetrators (67.2% of 4722 respondents in 5 studies) and women the most common victims (56.2% of 15 246 respondents in 27 studies). Only a minority of victims (28.9% of 9410 victims in 25 studies) reported the bullying, and most (57.5%) did not perceive a positive outcome. Facilitators of bullying included lack of enforcement of institutional policies (reported in 13 studies), hierarchical power structures (7 studies) and normalisation of bullying (10 studies). Studies testing the effectiveness of anti-bullying interventions had a high risk of bias.Conclusions Academic bullying commonly involved overwork, had a negative impact on well-being and was not typically reported. Perpetrators were most commonly consultants and men across career stages, and victims were commonly women. Methodologically robust trials of anti-bullying interventions are needed.Limitations Most studies (40 of 68) had at least a moderate risk of bias. All interventions were tested in uncontrolled before–after studies.