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Background: Haemodialysis access patterns differ internationally. This can not only be explained by differences in patient cohorts. What is considered the right access for the right patient is debated and it is unclear which patient-related factors affect the choice of access. The aim of the study was to investigate how patient-specific factors as body size and comorbidities influenced the choice of haemodialysis access in a real-life setting.

Methods: Retrospective cohort study including all patients receiving a haemodialysis access in Sweden between 2013 and 2022. Data from the Swedish Renal Registry (SNR) and the National Patient Register (NPR) was used. Data regarding age, sex, cause of kidney failure, previous kidney replacement therapy, height and weight (after dialysis), were collected from SNR. Data on comorbidities were extracted both from SNR and the NPR. AV-accesses were grouped into four categories depending on location of artery. Changes in arteriovenous access creation over time and patient-related factors affecting the choice of first access were analysed.

Results: Of 10,170 patients, 9706 with 17,709 accesses were included. The creation of upper-arm fistulas (p = 0.042) and arteriovenous grafts (p = 0.007) increased. Small body size, female sex, diabetes mellitus, vintage, previous haemodialysis treatment (all p < 0.001), age (p = 0.002) and peripheral arterial disease (p = 0.031) led to more central venous catheters. Small body size, female sex, peripheral arterial disease, vintage, previous haemodialysis treatment (all p < 0.001) and diabetes mellitus (p = 0.023) decreased the probability for selecting a forearm fistula. Upper-arm fistulas were preferred over arteriovenous grafts for those with small body size (p < 0.001 for body surface area), female sex (p = 0.003) and previous haemodialysis (p < 0.001).

Conclusions: The use of upper-arm fistulas and arteriovenous grafts is increasing, while forearm arteriovenous fistulas remain the primary access modality. Patient-related factors influencing the choice of access seemed to be related to vessel size and quality, rather than age and cardiovascular comorbidities.

Importance: Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown.

Objective: To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening.

Design, Setting, and Participants: Cross-sectional study of a population-based cohort of women in Sweden (n = 10 528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected.

Exposures: Adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm delivery, small-for-gestational-age infant, and gestational diabetes. The reference category included women with no history of these exposures.

Main Outcomes and Measures: Coronary computed tomography angiography indexes, including any coronary atherosclerosis, significant stenosis, noncalcified plaque, segment involvement score of 4 or greater, and coronary artery calcium score greater than 100. Results: A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk.

Conclusions and Relevance: Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.

Introduction: Mineralocorticoid receptor antagonists (MRAs) reduce mortality and morbidity in patients with heart failure and reduced ejection fraction (HFrEF), but are largely underused. We evaluated the frequency, motives, predictors and outcomes of MRA discontinuation in a real-world heart failure population.

Methods and results: This was a single-centre, retrospective cohort study where medical record-based data were collected on patients with HFrEF between 2010 and 2018. In the final analysis, 572 patients were included that comprised the continued MRA group (n=275) and the discontinued MRA group (n=297). Patients that discontinued MRA were older, had a higher comorbidity index and a lower index estimated glomerular filtration rate (eGFR). Predictors of MRA discontinuations were increased S-potassium, lower eGFR, lower systolic blood pressure, higher frequency of comorbidities and a higher left ventricular ejection fraction. The most common reason for MRA discontinuation was renal dysfunction (n=97, 33%) with 59% of these having an eGFR <30 mL/min/1.73m 2, and elevated S-potassium (n=71, 24%) with 32% of these having an S-potassium >5.5 mmol/L. Discontinuation of MRA increased the adjusted risk of all-cause mortality (HR 1.48; 95% CI 1.07 to 2.05; p=0.019).

Conclusions: Half of all patients with HFrEF initiated on MRA discontinued the treatment. A substantial number of patients discontinued MRA without meeting the guideline-recommended levels of eGFR and S-potassium where mild to moderate hyperkalaemia seems to be the most decisive predictor. Further, MRA discontinuation was associated with increased adjusted risk of all-cause mortality.

Purpose: To develop a model for systematic introduction and to test the feasibility in a chronic disease population. We also investigated how the approach was received by the patients.

Methods and results: The systematic introduction approach is a seven-step procedure: step 1, define a few main criteria; step 2, primary scan patients with the one or two main criteria using computerized medical records/databases/clinical registries; step 3, identify patients applying the other predefined criteria; step 4, evaluate if any examinations/laboratory test updates are required; step 5, summon identified patients to the clinic with an information letter; step 6, discuss treatment with the patient and prescribe if appropriate; and step 7, follow up on initiated therapy and evaluate the applied process. The model was tested in a case study during introduction of the new drug sacubitril-valsartan in a heart failure population. In total, 76 out of 1924 patients were identified to be eligible for sacubitril-valsartan and summoned to the clinic to discuss treatment. Patient experiences with the approach were investigated in an interview study with general inductive approach using qualitative content analysis. This resulted in three final categories: a good approach, role of the information letter, and trust in care.

Conclusions: The systematic introduction approach ensures that strict criteria are used in the selection process and that a treatment can be implemented in eligible patients within a specified population with limited resources and time. The model was effective in our case study and maintained the patient's confidence in healthcare.

Background: The risk of heart failure among diabetic individuals is high, even under tight glycemic control. The correlates and mediators of heart failure risk in individuals with diabetes need more elucidation in large population-based cohorts with long follow-up times and a wide panel of biologically relevant biomarkers.

Methods: In a population-based sample of 3834 diabetic and 90,177 non-diabetic individuals, proportional hazards models and mediation analysis were used to assess the relation of conventional heart failure risk factors and biomarkers with incident heart failure.

Results: Over a median follow-up of 13.8 years, a total of 652 (17.0%) and 5524 (6.1%) cases of incident heart failure were observed in participants with and without diabetes, respectively. 51.4% were women and the mean age at baseline was 48.7 (standard deviation [SD] 12.5) years. The multivariable-adjusted hazard ratio (HR) for heart failure among diabetic individuals was 2.70 (95% confidence interval, 2.49–2.93) compared to non-diabetic participants. In the multivariable-adjusted Cox models, conventional cardiovascular disease risk factors, such as smoking (diabetes: HR 2.07 [1.59–2.69]; non-diabetes: HR 1.85 [1.68–2.02]), BMI (diabetes: HR 1.30 [1.18–1.42]; non-diabetes: HR 1.40 [1.35–1.47]), baseline myocardial infarction (diabetes: HR 2.06 [1.55–2.75]; non-diabetes: HR 2.86 [2.50–3.28]), and baseline atrial fibrillation (diabetes: HR 1.51 [0.82–2.80]; non-diabetes: HR 2.97 [2.21–4.00]) had the strongest associations with incident heart failure. In addition, biomarkers for cardiac strain (represented by nT-proBNP, diabetes: HR 1.26 [1.19–1.34]; non-diabetes: HR 1.43 [1.39–1.47]), myocardial injury (hs-TnI, diabetes: HR 1.10 [1.04–1.16]; non-diabetes: HR 1.13 [1.10–1.16]), and inflammation (hs-CRP, diabetes: HR 1.13 [1.03–1.24]; non-diabetes: HR 1.29 [1.25–1.34]) were also associated with incident heart failure. In general, all these associations were equally strong in non-diabetic and diabetic individuals. However, the strongest mediators of heart failure in diabetes were the direct effect of diabetes status itself (relative effect share 43.1% [33.9–52.3] and indirect effects (effect share 56.9% [47.7-66.1]) mediated by obesity (BMI, 13.2% [10.3–16.2]), cardiac strain/volume overload (nT-proBNP, 8.4% [-0.7–17.4]), and hyperglycemia (glucose, 12.0% [4.2–19.9]).

Conclusions: The findings suggest that the main mediators of heart failure in diabetes are obesity, hyperglycemia, and cardiac strain/volume overload. Conventional cardiovascular risk factors are strongly related to incident heart failure, but these associations are not stronger in diabetic than in non-diabetic individuals. Active measurement of relevant biomarkers could potentially be used to improve prevention and prediction of heart failure in high-risk diabetic patients.

Aims: Impaired renal function is a major contributor to the low proportion of mineralocorticoidreceptor antagonist (MRA) treatment in patients with heart failure with reduced ejection fraction(HFrEF). Our aims were to investigate the impact of MRA treatment on all-cause mortalityand worsening renal function (WRF) in patients with HFrEF and moderately impairedrenal function.

Methods: Retrospective data between 2010–2018 on HFrEF patients from a single-centre hospitalwith estimated glomerular renal function (eGFR) < 60 ml/min/1.73 m2 were analysed. WRF was defined as a decline of by eGFR > 20%.

Results: 416 patients were included, 131 patients on MRA and 285 without MRA, mean age was 77years (SD ± 9) and 82 years (SD ± 9), respectively. Median follow-up was 2 years. 128patients (32%) experienced WRF, 25% in the MRA group and 30% in patients without MRA(p = 0.293). In multivariable analysis, hospitalization for heart failure and systolic blood pressurewere associated with WRF (p = 0.015 and p = <0.001), but not use of MRA (p = 0.421).MRA treatment had no impact on the risk of adjusted all-cause mortality (HR 0.93; 95% CI,0.66–1.32 p = 0.685). WRF was associated with increased adjusted risk of all-cause mortality(HR 1.43; 95% CI, 1.07–1.89 p = 0.014). Use of MRA did not increase the adjusted overallrisk of mortality even when experiencing WRF (HR 1.15; 95% CI, 0.81–1.63 p = 0.422).

Conclusion: In this cohort of elderly HFrEF patients with moderately impaired renal function, MRA didnot increase risk for WRF or all-cause mortality.

Aims: Glomerular filtration rate is an important factor in management of heart failure (HF). Our objective was to validate eight creatinine-based equations for estimating glomerular filtration rate (eGFR) in an HF population against measured glomerular filtration rate.

Methods and results: One hundred forty-six HF patients (mean age 68 +/- 13 years, mean left ventricular ejection fraction 45% +/- 15) within a single-centre hospital that underwent Cr-51-EDTA clearance between 2010 and 2018 were included in this retrospective study. eGFR was estimated by means of Cockcroft-Gault ideal and actual weight, the Modification of Diet in Renal Disease Study (MDRD), simplified MDRD with isotope dilution mass spectroscopy traceable calibration, the Chronic Kidney Disease Epidemiology Collaboration, revised Lund-Malmo, full age spectrum, and the Berlin Initiative Study 1. Mean measured glomerular filtration rate was 42 mL/min/1.73 m(2). Pearson's correlation coefficient (r) had the highest precision for MDRD (r = 0.9), followed by revised Lund-Malmo (r = 0.88). All equations except MDRD (mean difference -4.8%) resulted in an overestimation of the renal function. The accuracy was below 75% for all equations except MDRD.

Conclusions: None of the exclusively creatinine-based methods was accurate in predicting eGFR in HF patients. Our findings suggest that more accurate methods are needed for determining eGFR in patients with HF.

Purpose: The aims of this study were to examine sex differences in a heart failure population with regards to treatment and patient characteristics and to investigate the impact of sex on achieved doses of heart failure medications.

Methods and results: A total of 1924 patients with heart failure in a regional hospital were analysed, 622 patients had ejection fraction <= 40% of which 30% were women. In patients with reduced ejection fraction, women were older (79 +/- 11 vs. 74 +/- 12 years, P < 0.001), had lower body weight (70 +/- 17 vs. 86 +/- 18 kg, P < 0.001), lower estimated glomerular filtration rate (eGFR) (49 +/- 24 vs. 71 +/- 30 ml/min, P < 0.001) and received lower doses of heart failure medications than men. Multivariable linear regression on patients with reduced ejection fraction showed that sex was not associated with achieved dose of any heart failure medication. For angiotensin-converting enzyme inhibitors and angiotensin receptor blockers associated factors were eGFR, systolic blood pressure, age, ejection fraction, and heart rate. For beta-blockers associated factors were body weight, atrial fibrillation and age. For mineralocorticoid receptor antagonists associated factors were eGFR, serum potassium, age, systolic blood pressure, ejection fraction and heart rate.

Conclusion: Women with heart failure and reduced ejection fraction were prescribed lower doses of heart failure medications, were older, had worse renal function, and lower body weight than men. Sex was not independently associated with achieved doses of heart failure medications, instead age, renal function and body weight explained the differences in treatment.

Aim. Sacubitril-valsartan has proven beneficial in heart failure with reduced ejection fraction. Guidelines recommend initiating half-dose sacubitril-valsartan before up-titration even to patients already on target dose angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). To reduce the number of titration steps needed in order to simplify for the patient as well as the clinic, we aimed to investigate the safety and tolerability of switching patients on target dose ACE inhibitors or ARBs directly to maximum-dose sacubitril-valsartan. Methods. This prospective cohort study was conducted between April 2016 and November 2017. A total of 66 patients with heart failure and reduced ejection fraction already on guideline-recommended target dose ACE inhibitors or ARBs (equivalent to enalapril 10 mg twice daily) were switched to maximum-dose sacubitril-valsartan (200 mg twice daily). The patients were followed for twelve months. Results. Patients had a mean age of 72 +/- 10 years, mean systolic blood pressure of 121 +/- 17 mmHg, and 92% were male. At 12-month follow-up, nine patients (14%) had discontinued sacubitril-valsartan, four patients (6%) had a dose reduction, and 17 patients (26%) had developed symptomatic hypotension. No angioedema occurred within the 12-month follow-up and there were no hospitalizations or emergency room visits within the first 14 days. Conclusions. Switching directly from target dose ACE inhibitors or ARBs to maximum-dose sacubitril-valsartan was safe and generally well tolerated.

Aims: This study aims to investigate the eligibility of the Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor (ARNI) with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM‐HF) study to a real‐world heart failure population.

Methods and results: Medical records of all heart failure patients living within the catchment area of Umeå University Hospital were reviewed. This district consists of around 150 000 people. Out of 2029 patients with a diagnosis of heart failure, 1924 (95%) had at least one echocardiography performed, and 401 patients had an ejection fraction of ≤35% at their latest examination. The major PARADIGM‐HF criteria were applied, and 95 patients fulfilled all enrolment criteria and thus were eligible for sacubitril–valsartan. This corresponds to 5% of the overall heart failure population and 24% of the population with ejection fraction ≤ 35%. The eligible patients were significantly older (73.2 ± 10.3 vs. 63.8 ± 11.5 years), had higher blood pressure (128 ± 17 vs. 122 ± 15 mmHg), had higher heart rate (77 ± 17 vs. 72 ± 12 b.p.m.), and had more atrial fibrillation (51.6% vs. 36.2%) than did the PARADIGM‐HF population.

Conclusions: Only 24% of our real‐world heart failure and reduced ejection fraction population was eligible for sacubitril–valsartan, and the real‐world heart failure and reduced ejection fraction patients were significantly older than the PARADIGM‐HF population. The lack of data on a majority of the patients that we see in clinical practice is a real problem, and we are limited to extrapolation of results on a slightly different population. This is difficult to address, but perhaps registry‐based randomized clinical trials will help to solve this issue.