Patient profile and outcomes associated with follow-up in specialty vs. primary care in heart failure.

AIMS: Factors influencing follow-up referral decisions and their prognostic implications are poorly investigated in patients with heart failure (HF) with reduced (HFrEF), mildly reduced (HFmrEF), and preserved (HFpEF) ejection fraction (EF). We assessed (i) the proportion of, (ii) independent predictors of, and (iii) outcomes associated with follow-up in specialty vs. primary care across the EF spectrum. METHODS AND RESULTS: We analysed 75 518 patients from the large and nationwide Swedish HF registry between 2000-2018. Multivariable logistic regression models were fitted to identify the independent predictors of planned follow-up in specialty vs. primary care, and multivariable Cox models to assess the association between follow-up type and outcomes. In this nationwide registry, 48 115 (64%) patients were planned for follow-up in specialty and 27 403 (36%) in primary care. The median age was 76 [interquartile range (IQR) 67-83] years and 27 546 (36.5%) patients were female. Key independent predictors of planned follow-up in specialty care included optimized HF care, that is follow-up in a nurse-led HF clinic [odds ratio (OR) 4.60, 95% confidence interval (95% CI) 4.41-4.79], use of HF devices (OR 3.99, 95% CI 3.62-4.40), beta-blockers (OR 1.39, 95% CI 1.32-1.47), renin-angiotensin system/angiotensin-receptor-neprilysin inhibitors (OR 1.21, 95% CI 1.15-1.27), and mineralocorticoid receptor antagonists (OR 1.31, 95% CI 1.26-1.37); and more severe HF, that is higher NT-proBNP (OR 1.13, 95% CI 1.06-1.20) and NYHA class (OR 1.13, 95% CI 1.08-1.19). Factors associated with lower likelihood of follow-up in specialty care included older age (OR 0.29, 95% CI 0.28-0.30), female sex (OR 0.89, 95% CI 0.86-0.93), lower income (OR 0.79, 95% CI 0.76-0.82) and educational level (OR 0.77, 95% CI 0.73-0.81), higher EF [HFmrEF (OR 0.65, 95% CI 0.62-0.68) and HFpEF (OR 0.56, 95% CI 0.53-0.58) vs. HFrEF], and higher comorbidity burden, such as presence of kidney disease (OR 0.91, 95% CI 0.87-0.95), atrial fibrillation (OR 0.85, 95% CI 0.81-0.89), and diabetes mellitus (OR 0.92, 95% CI 0.88-0.96). A planned follow-up in specialty care was independently associated with lower risk of all-cause [hazard ratio (HR) 0.78, 95% CI 0.76-0.80] and cardiovascular death (HR 0.76, 95% CI 0.73-0.78) across the EF spectrum, but not of HF hospitalization (HR 1.06, 95% CI 1.03-1.10). CONCLUSIONS: In a large nationwide HF population, referral to specialty care was linked with male sex, younger age, lower EF, lower comorbidity burden, better socioeconomic environment and optimized HF care, and associated with better survival across the EF spectrum. Our findings highlight the need for greater and more equal access to HF specialty care and improved quality of primary care.

Young patients with heart failure: clinical characteristics and outcomes. Data from the Swedish Heart Failure, National Patient, Population and Cause of Death Registers.

AIMS: The prevalence and hospitalizations of patients with heart failure (HF) aged <55 years have increased in Sweden during the last decades. We aimed to compare characteristics of younger and older patients with HF, and examine survival in patients <55 years compared with matched controls. METHODS AND RESULTS: All patients ≥18 years in the Swedish Heart Failure Register from 2003 to 2014 were included. Data were merged with National Patient and Cause of Death Registers. Among 60 962 patients, 3752 (6.2%) were <55 years, and were compared with 7425 controls from the Population Register. Compared with patients ≥55 years, patients <55 years more frequently had registered diagnoses of obesity, dilated cardiomyopathy, congenital heart disease, and an ejection fraction <40% (9.8% vs. 4.7%, 27.2% vs. 5.5%, 3.7% vs. 0.8%, 67.9% vs. 45.1%, respectively; all P < 0.001). One-year all-cause mortality was 21.2%, 4.2%, and 0.3% in patients ≥55 years, patients <55 years, and controls <55 years, respectively (all P < 0.001). Patients <55 years had a five times higher mortality risk compared with controls [hazard ratio (HR) 5.48, 95% confidence interval (CI) 4.45-6.74]; the highest HR was in patients 18-34 years (HR 38.3, 95% CI 8.70-169; both P < 0.001). At the age of 20, the estimated life-years lost was up to 36 years for 50% of patients, with declining estimates with increasing age. CONCLUSION: Patients with HF <55 years had different comorbidities than patients ≥55 years. The highest mortality risk relative to that of controls was among the youngest patients.

Prevalence of, associations with, and prognostic role of anemia in heart failure across the ejection fraction spectrum.

BACKGROUND: The role of anemia in heart failure with mid-range and preserved ejection fraction (HFmrEF, EF 40-49% and HFpEF, EF ≥50%) is unknown. We aimed to compare prevalence of, associations with, and prognostic role of anemia in HF across the EF spectrum. METHODS: In patients from the Swedish HF Registry, we assessed the associations between clinical characteristics and anemia (hemoglobin <120 g/L in women and <130 g/L in men) by multivariable logistic regression, and between anemia, composite of all-cause death and HF hospitalization and all-cause death alone by multivariable Cox regression. RESULTS: Of 49,985 patients with HF (anemia = 34%), 23% had HFpEF (anemia = 41%), 21% had HFmrEF (anemia = 35%) and 55% had HFpEF (anemia = 32%). Higher EF was independently associated with higher likelihood of concomitant anemia. Important predictors of anemia across the EF spectrum were male sex, older age, worse New York Heart Association class and renal function, lower systolic blood pressure, higher N-Terminal B-type natriuretic peptides levels, diabetes, valvular disease and in-patient status. Anemia had adjusted hazard ratios (95% CI) for mortality or HF hospitalization 1.24 (1.18-1.30) in HFpEF, 1.26 (1.19-1.34) in HFmrEF and 1.14 (1.10-1.19) in HFrEF; pinteractionEF = 0.003; and for mortality 1.28 (1.20-1.36) in HFpEF, 1.21 (1.13-1.29) in HFmrEF, and 1.30 (1.24-1.35) in HFrEF; pinteractionEF = 0.22. CONCLUSIONS: In this nation-wide registry, prevalence of anemia was higher in HFpEF vs. HFmrEF vs. HFrEF, but was associated with a similarly increased risk of death across the EF spectrum, with greater risk of death or HF hospitalization in HFpEF and HFmrEF vs. HFrEF.

Limited value of NT-proBNP as a prognostic marker of all-cause mortality in patients with heart failure with preserved and mid-range ejection fraction in primary care: A report from the swedish heart failure register.

Aim: The prognostic value of natriuretic peptides in the management of heart failure (HF) patients with ejection fraction (EF) <40% is well established, but is less known for those with EF ≥40% managed in primary care (PC). Therefore, the aim of this study is to describe the prognostic significance of plasma NT-proBNP in such patients managed in PC.Subjects: We included 924 HF patients (48% women) with EF ≥40% and NT-proBNP registered in the Swedish Heart Failure Registry. Follow-up was 1100 ± 687 days.Results: One-, three- and five-year mortality rates were 8.1%, 23.9% and 44.7% in patients with EF 40-50% (HFmrEF) and 7.3%, 23.6% and 37.2% in patients with EF ≥50% (HFpEF) (p = 0.26). Patients with the highest mean values of NT-proBNP had the highest all-cause mortality but wide standard deviations (SDs). In univariate regression analysis, there was an association only between NT-proBNP quartiles and all-cause mortality. In HFmrEF patients, hazard ratio (HR) was 1.96 (95% CI 1.60-2.39) p < 0.0001) and in HFpEF patients, HR was 1.72 (95% CI 1.49-1.98) p < 0.0001). In a multivariate Cox proportional hazard regression analysis, adjusted for age, NYHA class, atrial fibrillation and GFR class, this association remained regarding NT-proBNP quartiles [HR 1.83 (95% CI 1.38-2.44), p < 0.0001] and [HR 1.48 (95% CI 1.16-1.90), p = 0.0001], HFmrEF and HFpEF, respectively.Conclusion: NT-proBNP has a prognostic value in patients with HF and EF ≥40% managed in PC. However, its clinical utility is limited due to high SDs and the fact that it is not independent in this population which is characterized by high age and much comorbidity.Key pointsIt is uncertain whether NT-proBNP predicts risk in heart failure with preserved ejection fraction (EF > 40%, HFpEF) managed in primary care.We show that high NT-proBNP predicts increased all-cause mortality in HFpEF-patients managed in primary care.The clinical use is however limited due to large standard deviations, many co-morbidities and high age.Many of these co-morbidities contribute to all-cause mortality and management of these patients should also focus on these co-morbidities.

The Swedish Heart Failure Registry: a living, ongoing quality assurance and research in heart failure.

Heart failure (HF) represents a global pandemic. Although in HF with reduced ejection fraction (HFrEF) randomized controlled trials have provided effective treatments, prognosis still remains poor, with signals of undertreatment. HF with mid-range EF (HFmrEF) has no evidence-based therapy, and its characterization is ongoing. Trials in HF with preserved EF (HFpEF) have failed to provide any effective treatment, but there are several concerns about their design. Thus, current challenges in the HF field are: 1) optimizing the use of existing treatments in HFrEF; 2) developing and proving efficacy of new treatments, and of new use of existing treatments in HFpEF and HFmrEF. Here we describe how registry-based research can improve knowledge addressing the unmet needs in HF, and in particular we focus on the contribution of the Swedish Heart Failure Registry to this field.

Type 2 diabetes and heart failure: Characteristics and prognosis in preserved, mid-range and reduced ventricular function.

OBJECTIVE: To study the characteristics and prognostic implications of type 2 diabetes in different heart failure entities from a nationwide perspective. METHODS: This observational study comprised 30,696 heart failure patients prospectively included in the Swedish Heart Failure Registry (SwedeHF) 2003-2011 from specialist care, with mortality information available until December 2014. Patients were categorized into three heart failure entities by their left ventricular ejection fraction (heart failure with preserved ejection fraction: ⩾50%, heart failure with mid-range ejection fraction: 40%-49% and heart failure with reduced ejection fraction: <40%). All-cause mortality stratified by type 2 diabetes and heart failure entity was studied by Cox regression. RESULTS: Among the patients, 22% had heart failure with preserved ejection fraction, 21% had heart failure with mid-range ejection fraction and 57% had heart failure with reduced ejection fraction. The proportion of type 2 diabetes was similar, ≈25% in each heart failure entity. Patients with type 2 diabetes and heart failure with preserved ejection fraction were older, more often female and burdened with hypertension and renal impairment compared with heart failure with mid-range ejection fraction and heart failure with reduced ejection fraction patients among whom ischaemic heart disease was more common. Type 2 diabetes remained an independent mortality predictor across all heart failure entities after multivariable adjustment, somewhat stronger in heart failure with left ventricular ejection fraction below 50% (hazard ratio, 95% confidence interval; heart failure with preserved ejection fraction: 1.32 [1.22-1.43], heart failure with mid-range ejection fraction: 1.51 [1.39-1.65], heart failure with reduced ejection fraction: 1.46 [1.39-1.54]; p-value for interaction, p = 0.0049). CONCLUSION: Type 2 diabetes is an independent mortality predictor across all heart failure entities increasing mortality risk by 30%-50%. In type 2 diabetes, the heart failure with mid-range ejection fraction entity resembles heart failure with reduced ejection fraction in clinical characteristics, risk factor pattern and prognosis.

Association of diuretic treatment at hospital discharge in patients with heart failure with all-cause short- and long-term mortality: A propensity score-matched analysis from SwedeHF.

AIMS: Diuretics are recommended for treating congestive symptoms in heart failure (HF). The short- and long-term prognostic effects of diuretic treatment at hospital discharge have not been studied in randomized clinical trials or in a Western world population. We aimed to determine the association of diuretic treatment at discharge with the risk of short-and long-term all-cause mortality in real-life patients in Sweden with HF irrespective of EF. METHODS AND RESULTS: From a Swedish nationwide HF register 26,218 patients discharged from hospital were included in the present study. A total of 87% of patients were treated with and 13% were not treated with diuretics at hospital discharge. In a 1:1 propensity score-matched cohort of 6564 patients, the association of diuretic treatment at hospital discharge with the risk of 90-day all-cause mortality was neutral (HR 0.89, 95% CI 0.74-1.07, p=0.21) whereas the risk of long-term all-cause mortality (median follow-up: 2.85years) was increased (HR 1.15, 95% CI 1.06-1.24, p<0.001). CONCLUSION: Diuretic treatment at hospital discharge was not associated with short-term mortality whereas it was associated with increased long-term mortality. Although we accounted for a wide range of clinical features, measured or unmeasured factors could still explain this increase in risk. However, our results suggest that diuretic treatment at hospital discharge may be regarded as a marker of increased long-term mortality.

Usefulness of Collagen Carboxy-Terminal Propeptide and Telopeptide to Predict Disturbances of Long-Term Mortality in Patients ≥60 Years With Heart Failure and Reduced Ejection Fraction.

Disturbances of collagen metabolism may alter the myocardial collagen network and contribute to cardiac remodeling and prognosis in heart failure (HF). Collagen type I synthesis and degradation can be assessed indirectly by the circulating biomarkers carboxy-terminal propeptide (PICP) and carboxy-terminal telopeptide (CITP), respectively. We examined the associations between PICP and CITP and long-term mortality in patients with HF. The Optimizing Congestive Heart Failure Outpatient Clinic (OPTIMAL) project studied patients aged ≥60 years with New York Heart Association class II to IV and HF with reduced ejection fraction (EF) hospitalized with acute HF during 1996 to 1999. On entry, mean age was 75 years, blood pressure 134/80 mm Hg, EF 34%, brain natriuretic peptide 312 pg/ml; 55% had atrial fibrillation. Dates of mortality were collected from administrative databases and medical records up until 2008. Follow-up was 9 to 13 years in all 132 patients, and mean survival was 5.5 ± 4.0 years. Baseline PICP tended to be higher, CITP was higher, and the PICP:CITP ratio was lower in the 102 deceased, compared with the 30 patients alive. Multivariable Cox regression analyses including 2 established risk factor models performed for all-cause (n = 101) and cardiovascular mortality (n = 61) show PICP and CITP to be independent predictors for all-cause and cardiovascular mortality. In conclusion, disturbances of collagen type I metabolism have independent prognostic implications for long-term all-cause and cardiovascular mortality in patients with HF with reduced EF. The results suggest excessive degradation to be the predominant disturbance associated with untoward prognosis and adds information on possible target mechanisms for future therapy.

Prognostic Implications of Type 2 Diabetes Mellitus in Ischemic and Nonischemic Heart Failure.

BACKGROUND: Heart failure (HF) is a common and serious complication in type 2 diabetes mellitus (T2DM). The prognosis of ischemic HF and impact of revascularization in such patients have not been investigated fully in a patient population representing everyday practice. OBJECTIVES: This study examined the impact of ischemic versus nonischemic HF and previous revascularization on long-term prognosis in an unselected population of patients with and without T2DM. METHODS: Patients stratified by diabetes status and ischemic or nonischemic HF and history of revascularization in the Swedish Heart Failure Registry (SwedeHF) from 2003 to 2011 were followed up for mortality predictors and longevity. A propensity score analysis was applied to evaluate the impact of previous revascularization. RESULTS: Among 35,163 HF patients, those with T2DM were younger, and 90% had 1 or more associated comorbidities. Ischemic heart disease (IHD) occurred in 62% of patients with T2DM and 47% of those without T2DM, of whom 53% and 48%, respectively, had previously undergone revascularization. T2DM predicted mortality regardless of the presence of IHD, with adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.40 (1.33 to 1.46) and 1.30 (1.22 to 1.39) in those with and without IHD, respectively. Patients with both T2DM and IHD had the highest mortality, which was further accentuated by the absence of previous revascularization (adjusted HR: 0.82 in favor of such treatment; 95% CI: 0.75 to 0.91). Propensity score adjustment did not change these results (HR: 0.87; 95% CI: 0.78 to 0.96). Revascularization did not abolish the impact of T2DM, which predicted mortality in those with (HR: 1.36; 95% CI: 1.24 to 1.48) and without (HR: 1.45; 95% CI: 1.33 to 1.56) a history of revascularization. CONCLUSIONS: Ninety percent of HF patients with T2DM have preventable comorbidities. IHD in patients with T2DM had an especially negative influence on mortality, an impact that was beneficially influenced by previous revascularization.

A comprehensive assessment of the association between anemia, clinical covariates and outcomes in a population-wide heart failure registry.

BACKGROUND: The aim was to investigate the prevalence of, predictors of, and association with mortality and morbidity of anemia in a large unselected cohort of patients with heart failure (HF) and reduced ejection fraction (HFrEF) and to explore if there were specific subgroups of high risk. METHODS: In patients with HFrEF in the Swedish Heart Failure Registry, we assessed hemoglobin levels and associations between baseline characteristics and anemia with logistic regression. Using propensity scores for anemia, we assessed the association between anemia and outcomes with Cox regression, and performed interaction and sub-group analyses. RESULTS: There were 24,511 patients with HFrEF (8303 with anemia). Most important independent predictors of anemia were higher age, male gender and renal dysfunction. One-year survival was 75% with anemia vs. 81% without (p < 0.001). In the matched cohort after propensity score the hazard ratio associated with anemia was for all-cause death 1.34 (1.28-1.40; p < 0.0001), CV mortality 1.28 (1.20-1.36; p < 0.0001), and combined CV mortality or HF hospitalization 1.24 (1.18-1.30; p < 0.0001). In interaction analyses, anemia was associated with greater risk with lower age, male gender, EF 30-39%, and NYHA-class I-II. CONCLUSION: In HFrEF, anemia is associated with higher age, male gender and renal dysfunction and increased risk of mortality and morbidity. The influence of anemia on mortality was significantly greater in younger patients, in men, and in those with more stable HF. The clinical implication of these findings might be in the future to perform targeted treatment studies.

Use of evidence-based therapy and survival in heart failure in Sweden 2003-2012.

AIMS: In heart failure with reduced ejection fraction, drug and device therapy improve survival. We studied contemporary trends in utilization of evidence-based therapy and associated survival. METHODS AND RESULTS: We studied 5908 patients with NYHA class II-IV heart failure, EF <30%, and duration of heart failure ≥6 months registered in the Swedish Heart Failure Registry between 2003 and 2012. Regression using generalized estimation equations was used to examine temporal trends in crude and risk-adjusted rates of utilization of evidence-based heart failure therapy and 30-day, 1-year, and 3-year survival. In 2003 vs. 2012, the risk-adjusted use of therapy and P-values for trends were as follows: renin-angiotensin system antagonists, 88% vs. 86% (P = 0.091); beta-blockers, 85% vs. 93% (P = 0.008); mineralocorticoid receptor antagonists, 53% vs. 42% (P < 0.001); CRT, 2.4% vs. 8.2% (P = 0.074); and implantable cardioverter-defibrillators, 4.0% vs. 10.7% (P = 0.004). During the same period, the risk-adjusted 30-day, 1-year, and 3-year survival was 92% vs. 94% (P = 0.532), 81% vs. 77% (P = 0.260), and 58% vs. 54% (P = 0.425), respectively. CONCLUSIONS: In this large nationwide registry, over the last decade the use of evidence-based drug therapy was high and remained stable over time, but, despite an increased use of device therapy, the absolute use was poor. This was associated with an absence of improvement in survival. The improvements in therapy and prognosis over the last generation may be levelling off, and efforts should be directed at improving implementation of evidence-based therapy.

Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of ≥50.

BACKGROUND: The pathophysiology of heart failure with preserved ejection fraction is poorly understood, but may involve a systemic proinflammatory state. Therefore, statins might improve outcomes in patients with heart failure with preserved ejection fraction defined as ≥50%. METHODS AND RESULTS: Of 46 959 unique patients in the prospective Swedish Heart Failure Registry, 9140 patients had heart failure and ejection fraction ≥50% (age 77±11 years, 54.0% women), and of these, 3427 (37.5%) were treated with statins. Propensity scores for statin treatment were derived from 40 baseline variables. The association between statin use and primary (all-cause mortality) and secondary (separately, cardiovascular mortality, and combined all-cause mortality or cardiovascular hospitalization) end points was assessed with Cox regressions in a population matched 1:1 based on age and propensity score. In the matched population, 1-year survival was 85.1% for statin-treated versus 80.9% for untreated patients (hazard ratio, 0.80; 95% confidence interval, 0.72-0.89; P<0.001). Statins were also associated with reduced cardiovascular death (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98; P=0.026) and composite all-cause mortality or cardiovascular hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.82-0.96; P=0.003). CONCLUSIONS: In heart failure with ejection fraction ≥50%, the use of statins was associated with improved outcomes. The mechanisms should be evaluated and the effects tested in a randomized trial.

Comparative associations between angiotensin converting enzyme inhibitors, angiotensin receptor blockers and their combination, and outcomes in patients with heart failure and reduced ejection fraction.

BACKGROUND: Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are recommended in heart failure with reduced ejection fraction (HFREF), but there is limited data on ARB vs. ACE-I and their combination in unselected populations. The purpose of this study was to compare the associations between the use of ACE-I, ARB and their combination, and outcomes in HFREF. METHODS AND RESULTS: We prospectively studied 22,947 patients with HFREF (ejection fraction<40%) enrolled in the Swedish Heart Failure Registry who received ACE-I but not ARB (n=15,801, 69%), ARB but not ACE-I (n=4335, 19%), their combination (n=571, 2%) or neither (n=2240, 10%). As compared with ACE-I alone, the hazard ratios (HRs) for ARB alone for all-cause mortality was 0.97 (95% CI=0.91-1.03; p=0.27), for HF hospitalization 1.08 (CI=1.02-1.15; p<0.01) and for the composite outcome 1.03 (CI=0.99-1.08; p=0.15). ACE-I and ARB combination had for death HR=0.98 (95% CI=0.84-1.14; p=0.76), for HF hospitalization HR=1.49 (CI=1.33-1.68; p<0.01) and for the composite outcome HR=1.35 (CI=1.21-1.50; p<0.01). Use of neither ACE-I nor ARB was associated with HR for death 1.41 (CI=1.33-1.50; p<0.01), for HF hospitalization 1.16 (CI=1.08-1.25; p<0.01) and for the composite outcome 1.28 (CI=1.21-1.35; p<0.01). CONCLUSION: This large generalizable analysis confirms the current recommendation of using ACE-I as first choice in HFREF. ARB can be considered an alternative in patients who cannot use ACE-I but should not routinely replace ACE-I. The combination of ACE-I and ARB was not associated with additional benefit over either one alone, and may potentially be harmful.

Risk factors, treatment and prognosis in men and women with heart failure with and without diabetes.

OBJECTIVE: To test the hypothesis that risk factor pattern, treatment and prognosis differ between men and women with heart failure (HF) with and without diabetes in the Swedish Heart Failure Registry. METHODS: Patients with (n=8809) and without (n=27 465) type 2 diabetes (T2DM) included in the Swedish Heart Failure Registry (2003-2011) were followed for mortality during a median follow-up of 1.9 years (range 0-8.7 years). All-cause mortality, differences in background and HF characteristics were analysed in women and men with and without T2DM and with a special regard to different age groups. RESULTS: Of 36 274 patients, 24% had T2DM and 39% were women. In patients with T2DM, women were older than men (78 years vs 73 years), more frequently had hypertension, renal dysfunction and preserved ventricular function. Regardless of T2DM status, women with reduced ventricular function, compared with their male counterparts, were less frequently offered, for example, ACE inhibitors/angiotensin receptor II blockers (ARB). Absolute mortality was 48% in women with T2DM, 40% in women without; corresponding male mortality rates were 43% and 35%, respectively. Kaplan-Meier curves revealed shorter longevity in women with T2DM but female sex did not remain a significant mortality predictor following adjustment (OR 95% CI 0.90; 0.79 to 1.03). In those without T2DM, women compared with men lived longer; this pattern remained after adjustment (OR 0.72; 0.66 to 0.78). T2DM was a stronger predictor of mortality in women (OR 1.72; 1.53 to 1.94) than in men (OR 1.47; 1.34 to 1.61). CONCLUSIONS: T2DM is a strong mortality predictor in men and women with HF, somewhat stronger in women. The shorter survival time in women with T2DM and HF related to comorbidities rather than sex per se. Evidence-based management was less prevalent in women. Mechanisms behind these findings remain incompletely understood and need further attention.

Association between renin-angiotensin system antagonist use and mortality in heart failure with severe renal insufficiency: a prospective propensity score-matched cohort study.

AIMS: In heart failure (HF) with reduced ejection fraction (EF), renin-angiotensin receptor (RAS) antagonists reduce mortality. However, severe renal insufficiency was an exclusion criterion in trials. We tested the hypothesis that RAS antagonists are associated with reduced mortality also in HF with severe renal insufficiency. METHODS AND RESULTS: We studied patients with EF ≤39% registered in the prospective Swedish Heart Failure Registry. In patients with creatinine >221 µmol/L or creatinine clearance <30 mL/min, propensity scores for RAS-antagonist use were derived from 36 variables. The association between RAS antagonist use and all-cause mortality was assessed with Cox regression in a cohort matched 1:1 based on age and propensity score. To assess consistency, we performed the same analysis as a 'positive control' in patients without severe renal insufficiency. Between 2000 and 2013, there were 24 283 patients of which 2410 [age, mean (SD), 82 (9), 45% women] had creatinine >221 µmol/L or creatinine clearance <30 mL/min and were treated (n = 1602) or not treated (n = 808) with RAS antagonists. In the matched cohort of 602 vs. 602 patients [age 83 (8), 42% women], RAS antagonist use was associated with 55% [95% confidence interval (CI) 51-59] vs. 45% (41-49) 1-year survival, P < 0.001, with a hazard ratio (HR) for mortality of 0.76 (95% CI 0.67-0.86, P < 0.001). In positive control patients without severe renal insufficiency [n = 21 873; age 71 (12), 27% women], the matched HR was 0.79 (95% CI 0.72-0.86, P < 0.001). CONCLUSION: In HF with severe renal insufficiency, the use of RAS antagonists was associated with lower all-cause mortality. Prospective randomized trials are needed before these findings can be applied to clinical practice.

Determinants of Utility Based on the EuroQol Five-Dimensional Questionnaire in Patients with Chronic Heart Failure and Their Change Over Time: Results from the Swedish Heart Failure Registry.

BACKGROUND: There is limited information on drivers of utilities in patients with chronic heart failure (CHF). OBJECTIVES: To analyze determinants of utility in CHF and drivers of change over 1 year in a large sample from clinical practice. METHODS: We included 5334 patients from the Swedish Heart Failure Registry with EuroQol five-dimensional questionnaire information available following inpatient or outpatient care during 2008 to 2010; 3495 had 1-year follow-up data. Utilities based on Swedish and UK value sets were derived. We applied ordinary least squares (OLS) and two-part models for utility at inclusion and OLS regression for change over 1 year, all with robust standard errors. We assessed the predictive accuracy of both models using cross-validation. RESULTS: Patients' mean age was 73 years, 65% were men, 19% had a left ventricular ejection fraction of 50% or more, 23% had 40% to 49%, 27% had 30% to 39%, and 31% had less than 30%. For both models and value sets, utility at inclusion was affected by sex, age, New York Heart Association class, ejection fraction, hemoglobin, blood pressure, lung disease, diabetes, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, nitrates, antiplatelets, and diuretics. The OLS model performed slightly better than did the two-part model on a population level and for capturing utility ranges. Change in utility over 1 year was influenced by age, sex, and (measured at inclusion) disease duration, New York Heart Association class, blood pressure, ischemic heart disease, lung disease, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and antiplatelets. CONCLUSIONS: Utilities in CHF and their change over time are influenced by diverse demographic and clinical factors. Our findings can be used to target clinical interventions and for economic evaluations of new therapies.

Association between use of statins and outcomes in heart failure with reduced ejection fraction: prospective propensity score matched cohort study of 21 864 patients in the Swedish Heart Failure Registry.

BACKGROUND: In heart failure (HF) with reduced ejection fraction, randomized trials of statins did not demonstrate improved outcomes. However, randomized trials may not always be generalizable. The aim was to determine whether statins are associated with improved outcomes in an unselected nationwide population of patients with HF with reduced ejection fraction overall and in relation to ischemic heart disease (IHD). METHODS AND RESULTS: In the Swedish Heart Failure Registry, 21 864 patients with HF with reduced ejection fraction (age ± SD, 72±12 years; 29% women), of whom 10 345 (47%) were treated with statins, were studied. Propensity scores for statin use were derived from 42 baseline variables. The associations between statin use and outcomes were assessed with Cox regressions in a population matched 1:1 based on propensity score and age and in the overall population with adjustment for propensity score and age. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular mortality; HF hospitalization; and combined all-cause mortality or cardiovascular hospitalization. Survival at 1 year in the matched population was 83% for statin-treated versus 79% for untreated patients (hazard ratio, 0.81; 95% confidence interval, 0.76-0.86; P<0.001). In the unmatched population, 1-year survival was 85% for statin-treated versus 79% for untreated patients, hazard ratio after adjustment for propensity score and age was 0.84 (95% confidence interval, 0.80-0.89; P<0.001). No examined baseline variables interacted with statin use except for IHD (P=0.001), with a hazard ratio of 0.76 (95% confidence interval, 0.70-0.82, P<0.001) with IHD and 0.95 (95% confidence interval, 0.85-1.07; P=0.430 without IHD. Statin use was also associated with reduced risk for all 3 secondary outcomes. CONCLUSIONS: In an unselected nationwide population of patients with HF with reduced ejection fraction, statins were associated with improved outcomes, specifically in the presence of IHD. This contrasts with previous randomized controlled trials. Additional randomized controlled trials with more generalized inclusion or focused on IHD may be warranted.

Gender, underutilization of cardiac resynchronization therapy, and prognostic impact of QRS prolongation and left bundle branch block in heart failure.

AIMS: It has been suggested that cardiac resynchronization therapy (CRT) is less utilized, dyssynchrony occurs at narrower QRS, and CRT is more beneficial in women compared with men. We tested the hypotheses that (i) CRT is more underutilized and (ii) QRS prolongation and left bundle branch block (LBBB) are more harmful in women. METHODS AND RESULTS: We studied 14 713 patients (28% women) with left ventricular ejection fraction (LVEF) <40% in the Swedish Heart Failure Registry. In women vs. men, CRT was present in 4 vs. 7% (P < 0.001) and was absent but with indication in 30 vs. 31% (P = 0.826). Next, among 13 782 patients (28% women) without CRT, 9% of women and 17% of men had non-specific intraventricular conduction delay (IVCD) and 27% of women and 24% of men had LBBB. One-year survival with narrow QRS was 85% in women and 88% in men, with IVCD 74 and 78%, and with LBBB 84 and 82%, respectively. Compared with narrow QRS, IVCD had a multivariable hazard ratio of 1.24 (95% CI 1.05-1.46, P = 0.011) in women and 1.30 (95% CI 1.19-1.42, P < 0.001) in men, and LBBB 1.03 (95% CI 0.91-1.16, P = 0.651) in women and 1.16 (95% CI 1.07-1.26, P < 0.001) in men, P for interaction between gender and QRS morphology, 0.241. CONCLUSIONS: While the proportion with CRT was lower in women, CRT was equally underutilized in both genders. QRS prolongation with or without LBBB was not more harmful in women than in men. Efforts to improve CRT implementation should be directed equally towards women and men.