Previous heart failure hospitalization, spironolactone, and outcomes in heart failure with preserved ejection fraction - a secondary analysis of TOPCAT.

BACKGROUND: Hospitalization for heart failure (HHF) is associated with poor postdischarge outcomes but the role of time since most recent HHF and potential treatment interactions are unknown. We aimed to assess history of and time since previous HHF, associations with composite of cardiovascular (CV) death and total HHF, first HHF and interactions with randomization to spironolactone, in heart failure with preserved ejection fraction. METHODS AND RESULTS: We assessed these objectives using uni- and multivariable regressions and spline analyses in TOPCAT-Americas. Among 1,765 patients, 66% had a previous HHF. Over a median of 2.9 years, 1,064 composite events of CV death or total HHFs occurred. Previous HHF was associated with more severe HF, and was independently associated with the composite outcome (HR 1.26, 95%CI 1.05-1.52, P = .014), and all secondary outcomes. A shorter time since most recent HHF appeared to be associated with subsequent first HHF, but not the composite of CV death or total HHF. Spironolactone had a significant interaction with previous HHF (interaction-P .046). Patients without a previous HHF had a larger effect of spironolactone on the composite outcome (HR 0.63, 95%CI 0.46-0.87, P = .005) than patients with a previous HHF (HR 0.91, 95%CI 0.78-1.06, P = .224). CONCLUSION: In TOPCAT-Americas, previous HHF was associated with CV death and first and total HHF. Duration since most recent HHF seemed to be associated with time to first HHF only. Spironolactone was associated with better outcomes in patients without a previous HHF. This interaction is hypothesis-generating and requires validation in future trials.

Left ventricular ejection fraction digit bias and reclassification of heart failure with mildly reduced vs reduced ejection fraction based on the 2021 definition and classification of heart failure.

AIMS: Aims were to evaluate (1) reclassification of patients from heart failure with mildly reduced (HFmrEF) to reduced (HFrEF) ejection fraction when an EF = 40% was considered as HFrEF, (2) role of EF digit bias, ie, EF reporting favouring 5% increments; (3) outcomes in relation to missing and biased EF reports, in a large multinational HF registry. METHODS AND RESULTS: Of 25,154 patients in the European Society of Cardiology (ESC) HF Long-Term registry, 17% had missing EF and of those with available EF, 24% had HFpEF (EF≥50%), 21% HFmrEF (40%-49%) and 55% HFrEF (<40%) according to the 2016 ESC guidelines´ classification. EF was "exactly" 40% in 7%, leading to reclassifying 34% of the HFmrEF population defined as EF = 40% to 49% to HFrEF when applying the 2021 ESC Guidelines classification (14% had HFmrEF as EF = 41% to 49% and 62% had HFrEF as EF≤40%). EF was reported as a value ending with 0 or 5 in ∼37% of the population. Such potential digit bias was associated with more missing values for other characteristics and higher risk of all-cause death and HF hospitalization. Patients with missing EF had higher risk of all-cause and CV mortality, and HF hospitalization compared to those with recorded EF. CONCLUSIONS: Many patients had reported EF = 40%. This led to substantial reclassification of EF from old HFmrEF (40%-49%) to new HFrEF (≤40%). There was considerable digit bias in EF reporting and missing EF reporting, which appeared to occur not at random and may reflect less rigorous overall care and worse outcomes.

Associations between rheumatoid arthritis, incident heart failure, and left ventricular ejection fraction.

BACKGROUND: Rheumatoid arthritis (RA) is an independent risk factor for heart failure (HF). Yet, the association between RA and left ventricular ejection fraction (LVEF) in incident HF is not well studied, nor are outcomes of HF in RA by LVEF. METHODS: We identified incident HF patients between 2003 and 2018 through the Swedish Heart Failure Registry, enriched with data from national health registers. Using logistic regression, associations between a prior diagnosis of RA and LVEF among HF patients and vs age, sex, and geographical area matched general population controls without HF were assessed. Additionally, associations between HF with vs without a prior diagnosis of RA, by LVEF, and outcomes up to 5 years after HF diagnosis were investigated using Cox regression. LVEF was primarily dichotomized at 40% and secondarily categorized as <40%, 40% to 49%, and ≥50%. Covariates included demographics and cardiovascular comorbidities. RESULTS: Among 20,916 incident HF patients, 331 (1.6%) had RA vs 1,047/103,501 (1.0%) of HF-free controls. The odds ratio (OR) for RA was 1.4 (95% CI: 1.1-1.8) in LVEF<40% vs HF-free controls and 1.6 (95% CI: 1.3-2.0) in LVEF≥40% vs HF-free controls. Among HF patients, RA was more common in HF with LVEF ≥40% (1.9%) vs LVEF<40% (1.3%), corresponding to OR 1.4 (95% CI: 1.1-1.7). No associations between RA and cardiovascular outcomes were observed across LVEF. An association between RA and all-cause mortality was observed only for patients with LVEF<40% (hazard ratio: 1.4; 95% CI: 1.1-1.8). CONCLUSIONS: RA was independently associated with incident HF, particularly HF with LVEF≥40%. RA did not associate with cardiovascular outcomes following HF diagnosis but was associated with increased risk of all-cause mortality in HF with LVEF<40%.

Eligibility for Dapagliflozin and Empagliflozin in a Real-world Heart Failure Population.

BACKGROUND: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), and EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with APreserved Ejection Fraction) trials. METHODS AND RESULTS: Selection criteria were applied to the Swedish HF registry outpatient population according to 3 scenarios: (i) a "trial scenario" applying all selection criteria; (ii) a "pragmatic scenario" applying the most clinically relevant criteria; and (iii) a "label scenario" following the regulatory agencies labels. Of the 49,317 patients, 55% had an ejection fraction of less than 40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had ejection fraction of 40% or greater and were assessed based on EMPEROR-Preserved and DELIVER. Eligibility using trial, pragmatic, and label scenarios was 35%, 61%, and 80% for DAPA-HF; 31%, 55%, and 81% for EMPEROR-Reduced; 30%, 61%, and 74% for DELIVER; and 32%, 59%, and 75% for EMPEROR-Preserved, respectively. The main selection criteria limiting eligibility were HF duration and N-terminal pro-B type natriuretic peptide levels. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality and morbidity.Clinical Highlights: Large clinical trials for the approval of new drugs in heart failure often apply numerous selection criteria, limiting the generalizability of trial findings to real-world populations. We assessed eligibility for dapagliflozin and empagliflozin according to trial criteria, the more practical criteria usually applied in daily practice for treatment selection, and the criteria mandated by regulatory agencies, in a real-word heart failure population. Our results from the Swedish Heart Failure Registry show that a great number of patients with heart failure might be candidates for these therapies, which have been shown to significantly decrease morbidity and mortality; therefore, their use should be implemented in clinical practice. LAY SUMMARY: When strictly applying selection criteria used in clinical trials, only one-third of a real-world heart failure population is eligible for treatment with empagliflozin and dapagliflozin. Adopting approaches that consider the most meaningful criteria, that is, those most clinically relevant or those mandated by regulatory agencies, significantly broadened eligibility. These results might contribute to future trial design taking into consideration the characteristics of real-world populations, feasibility, and potential cost benefits. CONCLUSIONS: In a real-world HF setting, eligibility for sodium glucose co-transporter-2 inhibitors was similar whether selection criteria from DAPA-HF or EMPEROR-Reduced were applied in HFrEF, or EMPEROR-Preserved or DELIVER in HFpEF. These data might help stakeholders assessing the consequences of future trial eligibility.

Cardiac resynchronization therapy with or without defibrillator in patients with heart failure.

AIMS: Randomized data on the efficacy/safety of cardiac resynchronization therapy with vs. without defibrillator (CRT-D,-P) in heart failure with reduced ejection fraction (HFrEF) are scarce. We aimed to evaluate survival associated with use of CRT-D vs. CRT-P in a contemporary cohort with HFrEF. METHODS AND RESULTS: Patients from Swedish HF Registry treated with CRT-D/CRT-P and fulfilling criteria for primary prevention defibrillator use were included. Logistic regression was used to evaluate predictors of CRT-D non-use. All-cause mortality was compared in CRT-D vs. CRT-P by Cox regression in a 1 : 1 propensity-score-matched cohort. Of 1988 patients with CRT, 1108 (56%) had CRT-D and 880 (44%) CRT-P. Older age, higher ejection fraction (EF), female sex, and the lack of referral to HF nurse-led outpatient clinic were major determinants of CRT-D non-use. After matching, 645 CRT-D patients were compared with 645 with CRT-P. The CRT-D use was associated with lower 1- and 3-year all-cause mortality [hazard ratio (HR):0.76, 95% confidence interval (CI):0.58-0.98; HR: 0.82, 95% CI: 0.68-0.99, respectively]. Results were consistent in all pre-specified subgroups except for CRT-D use being associated with lower 3-year mortality in patients with an EF < 30% but not in those with an EF ≥ 30% (HR: 0.73, 95% CI: 0.59-0.89 and HR: 1.24, 95% CI: 0.83-1.85, respectively; P-interaction = 0.02). CONCLUSION: In a contemporary HFrEF cohort, CRT-D was associated with lower mortality compared with CRT-P. The CRT-D use was less likely in older patients, females, and in patients not referred to HF nurse-led outpatient clinic. Our findings support the use of CRT-D vs. CRT-P in HFrEF, in particular with severely reduced EF.

Cryoablation of atypical atrioventricular nodal reentry tachycardia.

AIM: Data on ablation for atypical recurrent atrioventricular nodal reentry tachycardia (AVNRT) and long-term follow-up are generally sparse. Furthermore, the rate of recurrence and safety of cryoablation for atypical AVNRT has not been established. We compared patients cryoablated for atypical AVNRT and typical AVNRT during long-term follow-up. METHODS: All patients (n = 2612) who underwent catheter ablation for AVNRT at the Karolinska University Hospital between January 2009 and August 2019 were analyzed. A total of 91 patients undergoing first-time cryoablation for atypical AVNRT were included. A control group with first-time cryoablation for typical AVNRT was matched in a 1:1 ratio. Patients were followed-up for recurrences for a median of 5.0 years (interquartile range: 3.1-7.5 years). RESULTS: After 5 years, AVNRT recurrence occurred in 10 patients (11.0%) in the atypical AVNRT group and in 8 patients (8.8%) in the typical AVNRT group (hazard ratio: 1.31 [95% confidence interval: 0.52-3.32]; p = 0.568). The duration of the index procedure was significantly longer for atypical compared to typical AVNRT ablation (132.1 ± 49.2 min vs. 110.1 ± 38.8 min; p = 0.001). Transient AV blocks occurred in a similar fashion in the atypical compared to typical group (11 [12.1%] vs. 4 [4.9%]; p = 0.103). However, no ablation induced persistent AV block developed in either group. CONCLUSION: Cryoablation for atypical AVNRT showed similar rate of recurrences and safety compared to typical AVNRT during long-term follow-up.

Association Between ß-Blockers and Outcomes in Heart Failure With Preserved Ejection Fraction: Current Insights From the SwedeHF Registry.

BACKGROUND: ß-Blockers have an uncertain effect in heart failure with a preserved ejection fraction of 50% or higher (heart failure with preserved ejection fraction [HFpEF]). METHODS AND RESULTS: We included patients with HFpEF from the Swedish Heart Failure Registry (SwedeHF) enrolled from 2011 through 2018. In a 2:1 propensity-score matched analysis (ß-blocker use vs nonuse), we assessed the primary outcome first HF hospitalization, the coprimary outcome cardiovascular (CV) death, and the secondary outcomes of all-cause hospitalization and all-cause death. We performed intention-to-treat and a per-protocol consistency analyses. There were a total of 14,434 patients (median age 79 years, IQR 71-85 years, 51% women); 80% were treated with a ß-blocker at baseline. Treated patients were younger and had higher rates of atrial fibrillation and coronary artery disease, and higher N-terminal pro-B-type natriuretic peptide levels. In the 4412:2206 patient matched cohort, at 5 years, 42% (95% CI 40%-44%) vs 44% (95% CI 41%-47%) had a HF admission and 38% (IQR 36%-40%) vs 40% (IQR 36%-42%) died from CV causes. In the intention-to-treat analysis, ß-blocker use was not associated with HF admissions (hazard ratio 0.95 [95% CI 0.87-1.05, P = .31]) or CV death (hazard ratio 0.94 [95% CI 0.85-1.03, P = .19]). In the subgroup analyses, men seemed to have a more favorable association between ß-blockers and outcomes than did women. There were no associations between ß-blocker use and secondary outcomes. CONCLUSIONS: In patients with HFpEF, ß-blocker use is common but not associated with changes in HF hospitalization or cardiovascular mortality. In the absence of a strong rational and randomized control trials the case for ß-blockers in HFpEF remains inconclusive. BULLET POINTS: ● The effect of ß-blockers with heart failure with preserved ejection fraction of 50% or greater is uncertain.● In a propensity score-matched heart failure with preserved ejection fraction analysis in the SwedeHF registry, ß-blockers were not associated with a change in risk for heart failure admissions or cardiovascular deaths. LAY SUMMARY: The optimal treatment for heart failure with a preserved pump function remains unknown. Despite the lack of scientific studies, ß-blockers are very commonly used. When matching patients with a similar risk profile in a large heart failure registry, the use of ß-blockers for the treatment of heart failure with a preserved pump function was not associated with any changes in heart failure hospital admissions or cardiovascular death.

A population-based study of post-endovascular aortic repair rupture during 15 years.

OBJECTIVE: The devastating event of a ruptured abdominal aortic aneurysm (rAAA) in patients who have survived a previous AAA repair, either elective or urgent, is a feared and quite uncommon event. It has been suggested to partly explain the loss of the early survival benefit for endovascular aortic repair (EVAR) vs open surgical repair (OSR). The main objective of this study was to report the national incidence rate, risk factors and outcome of post-EVAR ruptures. Secondarily, the national incidence rate of ruptures after OSR (post-OSR ruptures) was investigated. METHODS: We conducted a nationwide, population-based, retrospective cohort study using the inpatient and outpatient entries for all patients >40 years of age, receiving their first (index) surgical procedure for AAA, from 2001 to 2015. Only patients surviving their index procedure were included. The primary outcome was rAAA, registered after discharge from the index procedure (EVAR or OSR), identified in the Swedish National Patient Registry and the Cause of Death Registry. RESULTS: In total, 14,859 patients survived their primary (index) AAA procedure. There were 6470 EVAR procedures, 5893 for intact AAA (iAAA) and 577 for rAAA. Of the 6470 EVAR patients, 86 cases of post-EVAR rupture were identified, corresponding with a cumulative incidence of 1.3% over a mean follow-up time of 3.9 years. The incidence rate was 3.4 (95% confidence interval [CI], 2.7-4.2)/1000 person-years. The independent risk factors identified for post-EVAR rupture were rAAA at index surgery HR 2.4 (95% CI, 1.4-4.1, p 0.002) and age (hazard ratio, 1.1; 95% CI, 1.0-1.1; P < .001). Freedom from post-EVAR rupture was 99%, 98%, and 96% at 3, 5, and 10 years, respectively. Total and postoperative mortality after post-EVAR rupture were 42% and 17% (30 days), 45% and 22% (90 days), and 53% and 33% (1 year). The incidence rate of post-OSR rupture was 0.9/1000 person-years (95% CI, 0.7-1.2). CONCLUSIONS: Post-EVAR rupture is a rare complication that can occur at any time after the index EVAR procedure. This finding may have implications for the discussion of limited follow-up programs and for the choice of procedure in patients with an AAA with a long life expectancy. An rAAA as the indication for the index surgery and age were identified as risk factors for post-EVAR rupture. The mortality associated with post-EVAR rupture is high, but lower than that of primary rAAA. The much lower risk of post-OSR rupture was confirmed, but must not be neglected as a possible late complication.

Association Between Use of Primary-Prevention Implantable Cardioverter-Defibrillators and Mortality in Patients With Heart Failure: A Prospective Propensity Score-Matched Analysis From the Swedish Heart Failure Registry.

BACKGROUND: Most randomized trials on implantable cardioverter-defibrillator (ICD) use for primary prevention of sudden cardiac death in heart failure with reduced ejection fraction enrolled patients >20 years ago. We investigated the association between ICD use and all-cause mortality in a contemporary heart failure with reduced ejection fraction cohort and examined relevant subgroups. METHODS: Patients from the Swedish Heart Failure Registry fulfilling the European Society of Cardiology criteria for primary-prevention ICD were included. The association between ICD use and 1-year and 5-year all-cause and cardiovascular (CV) mortality was assessed by Cox regression models in a 1:1 propensity score-matched cohort and in prespecified subgroups. RESULTS: Of 16 702 eligible patients, only 1599 (10%) had an ICD. After matching, 1305 ICD recipients were compared with 1305 nonrecipients. ICD use was associated with a reduction in all-cause mortality risk within 1 year (hazard ratio, 0.73 [95% CI, 0.60-0.90]) and 5 years (hazard ratio, 0.88 [95% CI, 0.78-0.99]). Results were consistent in all subgroups including patients with versus without ischemic heart disease, men versus women, those aged <75 versus ≥75 years, those with earlier versus later enrollment in the Swedish heart failure registry, and patients with versus without cardiac resynchronization therapy. CONCLUSIONS: In a contemporary heart failure with reduced ejection fraction population, ICD for primary prevention was underused, although it was associated with reduced short- and long-term all-cause mortality. This association was consistent across all the investigated subgroups. These results call for better implementation of ICD therapy.

Heart Failure in Patients Undergoing Elective and Emergency Noncardiac Surgery: Still a Poorly Addressed Risk Factor.

BACKGROUND: Noncardiac surgery is increasingly offered to an older, more comorbid population. The aim was to characterize patients with the diagnosis of heart failure (HF) undergoing elective and emergency noncardiac surgery in a broad, contemporary Swedish cohort, and to assess the short- and long-term mortality in patients with HF as compared with patients without HF. METHODS AND RESULTS: Data from 200,638 and 97,129 patients undergoing elective and emergency surgical procedures at 23 Swedish university, county, and district hospitals during 2007 to 2013 were analyzed through linkage of the surgical Orbit Database to the National Patient and the Cause of Death registries. In total 7212 patients (3.6%) with a diagnosis of HF before surgery underwent elective and 6455 patients (6.6%) underwent emergency surgery. Patients with HF were older had more comorbidities, and higher mortality than patients without HF. Crude and adjusted risk ratios for 30-day mortality after elective surgery were 5.36 (95% confidence interval [CI] 4.67-6.16) and 1.79 (95% CI 1.50-2.14) (adjusted for comorbidities, surgical risk level, age, and sex). Corresponding data for emergency surgery was 3.84 (95% CI 3.58-4.12) and 1.48 (95% CI 1.31-1.62). Mortality in patients with HF after elective surgery at 30 days, 90 days, and 1 year was 3.2%, 6.5%, and 16.2% and after emergency surgery it was 13.7%, 22.4%, and 39.3%. CONCLUSIONS: Patients with HF undergoing elective or emergency noncardiac surgery in a modern surgical setting have a substantial mortality risk and HF is both a risk factor and a strong marker for increasd risk. The reasons for the high mortality are not well-understood and warrant further attention.

Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study.

BACKGROUND: Coronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF. METHODS AND RESULTS: We assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54-159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0-68, P = .023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization. CONCLUSIONS: In this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV- and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.

Long-term outcome of patients with invasive electrophysiology procedure-related cardiac tamponade.

AIMS: Iatrogenic cardiac tamponades are a rare but dreaded complication of invasive electrophysiology procedures (EPs). Their long-term impact on clinical outcomes is unknown. This study analysed the risk of death or serious cardiovascular events in patients suffering from EP-related cardiac tamponade requiring pericardiocentesis during long-term follow-up. METHODS AND RESULTS: Out of 19 997 invasive EPs at the Karolinska University Hospital between January 1998 and September 2018, all patients with EP-related periprocedural cardiac tamponade were identified (n = 60) and matched (1:3 ratio) to a control group (n = 180). After a follow-up of 5 years, the composite primary endpoint - death from any cause, acute myocardial infarction, transitory ischaemic attack (TIA)/stroke, and hospitalization for heart failure - occurred in significantly more patients in the tamponade than in the control group [12 patients (20.0%) vs. 19 patients (10.6%); hazard ratio (HR) 2.53 (95% confidence interval, CI 1.15-5.58); P = 0.021]. This was mainly driven by a higher incidence of TIA/stroke in the tamponade than in the control group [HR 3.75 (95% CI 1.01-13.97); P = 0.049]. Death from any cause, acute myocardial infarction, and hospitalization for heart failure did not show a significant difference between the groups. Hospitalization for pericarditis occurred in significantly more patients in the tamponade than in the control group [HR 36.0 (95% CI 4.68-276.86); P = 0.001]. CONCLUSION: Patients with EP-related cardiac tamponade are at higher risk for cerebrovascular events during the first 2 weeks and hospitalization for pericarditis during the first months after index procedure. Despite the increased risk for early complications tamponade patients have a good long-term prognosis without increased risk for mortality or other serious cardiovascular events.

Fidelity Assessment of a Social Work-Led Intervention Among Patients with Firearm Injuries.

PURPOSE: To support future development and refinement of social work-led intervention programs among patients with firearm injuries and to demonstrate how a fidelity assessment can be used to adjust and refine intervention delivery in an ongoing trial. METHODS: We conducted a fidelity assessment of a randomized controlled trial of a social work-led intervention among patients with a firearm injury. RESULTS: We found that our study intervention was well implemented, meeting 70% of the fidelity assessment score items, however noted lower fidelity with client-based items. DISCUSSION: As a result of fidelity assessment findings, we refined intervention delivery to improve implementation fidelity including beginning to review cases of all patients each month, rather than focusing on patients in crisis. Our fidelity assessment process and findings offer insight into the challenges of implementing an intervention among patients with firearm injuries and highlights the value of monitoring intervention fidelity during an ongoing trial.

Alcohol-related hospitalization is associated with increased risk of ischaemic stroke among low-risk patients with atrial fibrillation.

Aims: Patients with atrial fibrillation (AF) under the age of 65 and CHA2DS2-VASc risk score of 0 in men or 1 in women are considered to be at low risk for ischaemic stroke, and therefore without benefit of oral anticoagulation therapy. The objective of this study is to assess the incidence and predictors of ischaemic stroke among low-risk patients with AF identified from a National Patient Register. Methods and results: A retrospective study of 25 252 low-risk AF patients (age 18-64) out of total 345 123 AF patients identified from the Swedish Nationwide Patient Register for the period 1 January 2006 to 31 December 2012. During a median follow-up of 5.0 (interquartile range 2.9-6.8) years, ischaemic stroke occurred at an annual rate of 0.34 per 100 patient-years [95% confidence interval (CI) 0.31-0.38]. Significant predictors of stroke were age, hazard ratio (HR) 1.06 (CI 1.05-1.08) per incremental year, and previous alcohol-related hospitalization HR 2.01 (CI 1.45-2.79). Intracerebral bleeding events were rare and not statistically different HR 2.05 (CI 0.76-5.56) between patients with and without alcohol-related hospitalizations. Use of oral anticoagulants was associated with lower risk for ischaemic stroke, HR 0.78 (CI 0.63-0.97). Conclusion: The presence of a previous hospitalization with an alcohol-related disease was associated with a small but significant increase in the risk of stroke among low-risk AF patients. More research about relation between alcohol use and ischaemic stroke in AF patients is warranted.

HFpEF and HFrEF Display Different Phenotypes as Assessed by IGF-1 and IGFBP-1.

BACKGROUND: Anabolic drive is impaired in heart failure with reduced ejection fraction (HFrEF) but insufficiently studied in heart failure with preserved ejection fraction (HFpEF). Insulin-like growth factor 1 (IGF-1) mediates growth hormone effects and IGF binding protein 1 (IGFBP-1) regulates IGF-1 activity. We tested the hypothesis that HFpEF and HFrEF are similar with regard to IGF-1 and IGFBP-1. METHODS AND RESULTS: In patients with HFpEF (n = 79), HFrEF (n = 85), and controls (n = 136), we analyzed serum IGF-1 and IGFBP-1 concentrations, correlations, and associations with outcome. Age-standardized scores of IGF-1 were higher in HFpEF, median arbitrary units (interquartile range); 1.21 (0.57-1.96) vs HFrEF, 0.09 (-1.40-1.62), and controls, 0.22 (-0.47-0.96), P overall <.001. IGFBP-1 was increased in HFpEF, 48 (28-79), and HFrEF, 65 (29-101), vs controls, 27(14-35) µg/L, P overall <.001. These patterns persisted after adjusting for metabolic and HF severity confounders. IGF-1 was associated with outcomes in HFrEF, hazard ratio per natural logarithmic increase in IGF-1 SD score 0.51 (95% confidence interval 0.32-0.82, P = .005), but not significantly in HFpEF. IGFBP-1 was not associated with outcomes in either HFpEF nor HFrEF. CONCLUSION: HFpEF and HFrEF phenotypes were similar with regard to increased IGFBP-1 concentrations but differed regarding IGF-1 levels and prognostic role. HFrEF and HFpEF may display different impairment in anabolic drive.

Clinical follow-up compared with self-assessment of outcome after medical abortion: a multicentre, non-inferiority, randomised, controlled trial.

BACKGROUND: Medical abortion with mifepristone and prostaglandins is well established. We compared clinical assessment with self-assessment of abortion outcome. METHODS: This randomised, controlled, non-inferiority trial was done in four clinics in Austria, Finland, Norway, and Sweden, between Aug 16, 2011, and Jan 31, 2013. Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation were eligible. Computer-generated block randomisation (block size ten) assigned women in a 1:1 ratio to attend routine clinical follow-up or to self-assess outcome at home with a semiquantitative urine human chorionic gonadotropin (hCG) test 1-3 weeks after abortion. The primary outcome was the percentage of women with complete abortion not requiring further medical or surgical intervention within 3 months. Analysis was per protocol and by intention to treat. The non-inferiority margin was five percentage points. This trial is registered with ClinicalTrials.gov, number NCT01487213. FINDINGS: 924 women were assigned routine follow-up (n=466) or self-assessment (n=458) and included in the intention-to-treat analysis. 901 were included in the per-protocol analysis (n=446 and n=455, respectively). Complete abortion was reported in 432 (95%) of 455 in the routine follow-up group and 419 (94%) of 446 women in the self-assessment group (crude difference -1·0, 95% CI -4·0 to 2·0). 20 (4%) women in the routine follow-up group and 17 (4%) in the self-assessment group required surgery. No women in the routine follow-up group versus three in the self-assessment group had undetected continuing pregnancies. Eight (1·8%) and one (0·2%) women, respectively, had infections (p=0·038). INTERPRETATION: Self-assessment was non-inferior to routine follow-up and could save resources. FUNDING: Nordic Federation of Obstetrics and Gynaecology, European Society of Contraception, Helsinki University Central Hospital, Helse Finnmark, Swedish Research Council, and Stockholm County Council and Karolinska University Hospital.

Immediate versus delayed insertion of an etonogestrel releasing implant at medical abortion-a randomized controlled equivalence trial.

STUDY QUESTION: Does a progestin releasing subdermal contraceptive implant affect the efficacy of medical abortion if inserted at the same visit as the progesterone receptor modulator, mifepristone, at medical abortion? SUMMARY ANSWER: A etonogestrel releasing subdermal implant inserted on the day of mifepristone did not impair the efficacy of the medical abortion compared with routine insertion at 2-4 weeks after the abortion. WHAT IS ALREADY KNOWN: The etonogestrel releasing subdermal implant is one of the most effective long acting reversible contraceptive methods. The effect of timing of placement on the efficacy of mifepristone and impact on prevention of subsequent unintended pregnancy is not known. STUDY DESIGN SIZE, DURATION: This multicentre, randomized controlled, equivalence trial with recruitment between 13 October 2013 and 17 October 2015 included a total of 551 women with pregnancies below 64 days gestation opting for the etonogestrel releasing subdermal implant as postabortion contraception. Women were randomized to either insertion at 1 hour after mifepristone intake (immediate) or at follow-up 2-4 weeks later (delayed insertion). An equivalence design was used due to advantages for women such as fewer visits to the clinic with immediate insertion. The primary outcome was the percentage of women with complete abortion not requiring surgical intervention within 1 month. Secondary outcomes included insertion rates, pregnancy and repeat abortion rates during 6 months follow-up. Analysis was per protocol and by intention to treat. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation and opted for an etonogestrel releasing contraceptive implant were recruited in outpatient family planning clinics in six hospitals in Sweden and Scotland. MAIN RESULTS AND THE ROLE OF CHANCE: Efficacy of medical abortion was 259/275 (94.2%) in the immediate insertion group and 239/249 (96%) in the routine insertion group with a risk difference of 1.8% (95% CI -0.4 to 4.1%), which was within the ±5% margin of equivalence. The insertion rate was 275/277 (98.9%) in the immediate group compared to 187/261 (71.6%) women in the routine group (P < 0.001). At 6 months of follow-up significantly fewer women in the immediate group had become pregnant again (2/277, 0.8%) compared to the routine group (10/261, 3.8%) P = 0.018. LIMITATIONS, REASONS FOR CAUTION: For the main outcome loss to follow-up data was minimized through access to patient records. Efforts were made to reduce loss to follow-up also for secondary outcomes. The results of the sensitivity analysis did not differ from the intention to treat or per protocol analysis. WIDER IMPLICATIONS OF THE FINDINGS: Guidelines on postabortion contraception should be amended to include insertion of the etonogestrel releasing implant at the time of mifepristone intake for medical abortion up to and including a gestation of 63 days. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Swedish Research Council (2012-2844), Stockholm City County and Karolinska Institutet (ALF). The contraceptive implants were provided by Merck and supplied by MSD Sweden. HKK and KGD have received honorariums for giving lectures for MSD/Merck and have participated in the national (HKK and KGD) and international (KGD) medical advisory boards for MSD/Merck. The other authors have nothing to declare. TRIAL REGISTRATION NUMBER: ClinicalTrials number NCT01920022. TRIAL REGISTRATION DATE: 06 August 2013. DATE OF FIRST PATIENT'S ENROLMENT: 13 October 2013.

Human leukocyte antigen class 1 genotype distribution and analysis in persons with active tuberculosis and household contacts from Central Uganda.

BACKGROUND: To determine the distribution of Human leukocyte antigen (HLA) class I genotypes in a Ugandan population of persons with tuberculosis (TB) and establish the relationship between class I HLA types and Mycobacterium tuberculosis (MTB) disease. METHODS: Blood samples were drawn from HIV negative individuals with active TB and HIV negative household controls. DNA was extracted from blood samples and HLA typed by the polymerase chain reaction-sequence specific primer method. The allelic frequencies were determined by direct count. RESULTS: HLA-A*02, B*15, C*07, C*03, B*58, C*04, A*01, A*74, C*02 and A*30 were the dominant genotypes in this Ugandan cohort. There were differences in the distribution of HLA types between the individuals with active TB and the household controls with only HLA-A*03 allele showing a statistically significant difference (p = 0.017 crude; OR = 6.29 and p = 0.016; OR = 11.67 after adjustment for age). However, after applying the Benjamini and Hochberg adjustment for multiple comparisons the difference was no longer statistically significant (p = 0.374 and p = 0.176 respectively). CONCLUSIONS: We identified a number of HLA class I alleles in a population from Central Uganda which will enable us to carry out a functional characterization of CD8+ T-cell mediated immune responses to MTB. Our results do not show a positive association between the HLA class I alleles and TB in this Ugandan population however the study sample was too small to draw any firm conclusions about the role of HLA class I alleles and TB development in Uganda.

Medication errors as malpractice-a qualitative content analysis of 585 medication errors by nurses in Sweden.

BACKGROUND: Many studies address the prevalence of medication errors but few address medication errors serious enough to be regarded as malpractice. Other studies have analyzed the individual and system contributory factor leading to a medication error. Nurses have a key role in medication administration, and there are contradictory reports on the nurses' work experience in relation to the risk and type for medication errors. METHODS: All medication errors where a nurse was held responsible for malpractice (n = 585) during 11 years in Sweden were included. A qualitative content analysis and classification according to the type and the individual and system contributory factors was made. In order to test for possible differences between nurses' work experience and associations within and between the errors and contributory factors, Fisher's exact test was used, and Cohen's kappa (k) was performed to estimate the magnitude and direction of the associations. RESULTS: There were a total of 613 medication errors in the 585 cases, the most common being "Wrong dose" (41 %), "Wrong patient" (13 %) and "Omission of drug" (12 %). In 95 % of the cases, an average of 1.4 individual contributory factors was found; the most common being "Negligence, forgetfulness or lack of attentiveness" (68 %), "Proper protocol not followed" (25 %), "Lack of knowledge" (13 %) and "Practice beyond scope" (12 %). In 78 % of the cases, an average of 1.7 system contributory factors was found; the most common being "Role overload" (36 %), "Unclear communication or orders" (30 %) and "Lack of adequate access to guidelines or unclear organisational routines" (30 %). The errors "Wrong patient due to mix-up of patients" and "Wrong route" and the contributory factors "Lack of knowledge" and "Negligence, forgetfulness or lack of attentiveness" were more common in less experienced nurses. The experienced nurses were more prone to "Practice beyond scope of practice" and to make errors in spite of "Lack of adequate access to guidelines or unclear organisational routines". CONCLUSIONS: Medication errors regarded as malpractice in Sweden were of the same character as medication errors worldwide. A complex interplay between individual and system factors often contributed to the errors.