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.

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.

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.

Atrial fibrillation and biomarkers of myocardial fibrosis in heart failure.

OBJECTIVES: Alterations of collagen metabolism present in heart failure promote the fibrotic substrate for the development of atrial fibrillation (AF). Myocardial collagen I synthesis and degradation can be assessed indirectly by circulating biomarkers such as the carboxy terminal propeptide (PICP) and carboxy-terminal telopeptide (CITP), respectively. DESIGN: We examined myocardial collagen type-I metabolism in 143 patients with systolic heart failure (New York Heart Association Class 2-4) in relation to coexisting AF. RESULTS: Mean age was 75 years, blood pressure 134/80 mm Hg, ejection fraction 34%, serum PICP 81 µg/L and CITP 8.3 µg/L, and median plasma brain natriuretic peptide 215 pg/L; 77 were in AF. PICP and CITP were related to left atrial diameter (r = 0.22, P = 0.013, and r = 0.26, P = 0.003) and CITP to pulmonary capillary wedge pressure and C-reactive protein (r = 0.19, P = 0.044, and r = 0.29, P = 0.003). A logistic regression suggested that PICP (odds ratio per 1 µg/L change 1.01, P = 0.012) and left ventricular end-diastolic volume (odds ratio per 1 mL change 0.98, P < 0.001) were independently associated with coexisting AF. CONCLUSION: Collagen type-I metabolism is associated to left atrial size. Heart failure patients with coexisting AF exhibit more altered collagen type-I metabolism than patients in sinus rhythm. This might represent more severe atrial and ventricular fibrosis.

Prevalence, correlates, and prognostic significance of QRS prolongation in heart failure with reduced and preserved ejection fraction.

AIMS: The independent clinical correlates and prognostic impact of QRS prolongation in heart failure (HF) with reduced and preserved ejection fraction (EF) are poorly understood. The rationale for cardiac resynchronization therapy (CRT) in preserved EF is unknown. The aim was to determine the prevalence of, correlates with, and prognostic impact of QRS prolongation in HF with reduced and preserved EF. METHODS AND RESULTS: We studied 25,171 patients (age 74.6 ± 12.0 years, 39.9% women) in the Swedish Heart Failure Registry. We assessed QRS width and 40 other clinically relevant variables. Correlates with QRS width were assessed with multivariable logistic regression, and the association between QRS width and all-cause mortality with multivariable Cox regression. Pre-specified subgroup analyses by EF were performed. Thirty-one per cent had QRS ≥120 ms. Strong predictors of QRS ≥120 ms were higher age, male gender, dilated cardiomyopathy, longer duration of HF, and lower EF. One-year survival was 77% in QRS ≥120 vs. 82% in QRS <120 ms, and 5-year survival was 42 vs. 51%, respectively (P < 0.001). The adjusted hazard ratio for all-cause mortality was 1.11 (95% confidence interval 1.04-1.18, P = 0.001) for QRS ≥120 vs. <120 ms. There was no interaction between QRS width and EF. CONCLUSION: QRS prolongation is associated with other markers of severity in HF but is also an independent risk factor for all-cause mortality. The risk associated with QRS prolongation may be similar regardless of EF. This provides a rationale for trials of CRT in HF with preserved EF.

Association between use of ß-blockers and outcomes in patients with heart failure and preserved ejection fraction.

IMPORTANCE: Heart failure with preserved ejection fraction (HFPEF) may be as common and may have similar mortality as heart failure with reduced ejection fraction (HFREF). ß-Blockers reduce mortality in HFREF but are inadequately studied in HFPEF. OBJECTIVE: To test the hypothesis that ß-blockers are associated with reduced all-cause mortality in HFPEF. DESIGN: Propensity score-matched cohort study using the Swedish Heart Failure Registry. Propensity scores for ß-blocker use were derived from 52 baseline clinical and socioeconomic variables. SETTING: Nationwide registry of 67 hospitals with inpatient and outpatient units and 95 outpatient primary care clinics in Sweden with patients entered into the registry between July 1, 2005, and December 30, 2012, and followed up until December 31, 2012. PARTICIPANTS: From a consecutive sample of 41,976 patients, 19,083 patients with HFPEF (mean [SD] age, 76 [12] years; 46% women). Of these, 8244 were matched 2:1 based on age and propensity score for ß-blocker use, yielding 5496 treated and 2748 untreated patients with HFPEF. Also we conducted a positive-control consistency analysis involving 22,893 patients with HFREF, of whom 6081 were matched yielding 4054 treated and 2027 untreated patients. EXPOSURES: ß-Blockers prescribed at discharge from the hospital or during an outpatient visit, analyzed 2 ways: without consideration of crossover and per-protocol analysis with censoring at crossover, if applicable. MAIN OUTCOMES AND MEASURES: The prespecified primary outcome was all-cause mortality and the secondary outcome was combined all-cause mortality or heart failure hospitalization. RESULTS: Median follow-up in HFPEF was 755 days, overall; 709 days in the matched cohort; no patients were lost to follow-up. In the matched HFPEF cohort, 1-year survival was 80% vs 79% for treated vs untreated patients, and 5-year survival was 45% vs 42%, with 2279 (41%) vs 1244 (45%) total deaths and 177 vs 191 deaths per 1000 patient-years (hazard ratio [HR], 0.93; 95% CI, 0.86-0.996; P = .04). ß-Blockers were not associated with reduced combined mortality or heart failure hospitalizations: 3368 (61%) vs 1753 (64%) total for first events, with 371 vs 378 first events per 1000 patient-years (HR, 0.98; 95% CI, 0.92-1.04; P = .46). In the matched HFREF cohort, ß-blockers were associated with reduced mortality (HR, 0.89; 95% CI, 0.82-0.97, P=.005) and also with reduced combined mortality or heart failure hospitalization (HR, 0.89; 95% CI, 0.84-0.95; P = .001). CONCLUSIONS AND RELEVANCE: In patients with HFPEF, use of ß-blockers was associated with lower all-cause mortality but not with combined all-cause mortality or heart failure hospitalization. ß-Blockers in HFPEF should be examined in a large randomized clinical trial.

Evaluation of an educational programme for family members of patients living with heart failure: a randomised controlled trial.

AIMS AND OBJECTIVES: To evaluate the effect of a group-based multi-professional educational programme for family members of patients with chronic heart failure with regard to quality of life, depression and anxiety. The secondary aim was to investigate the impact of social support and sense of coherence on changes in quality of life, anxiety and depression during the period of the study. BACKGROUND: When a person is diagnosed with heart failure, the daily life of the family members is also affected. DESIGN: Randomised controlled trial. METHODS: A total of 128 family members were randomly assigned to participate in a multi-professional educational programme or a control group. Analysis of variance and regression analysis were used. RESULTS: There were no significant differences in anxiety, depression or quality of life between the intervention group and control group. Adequacy of social network was the only independent variable that explained levels of anxiety and depression after 12 months beyond baseline levels of anxiety (p < 0·001, R(2) = 0·35) and depression (p = 0·021, R(2) = 0·37). Younger family members were found to have a higher quality of life (p < 0·01). CONCLUSION: Improved disease-related knowledge may need to be combined with other target variables to induce desired effects on depression, anxiety and quality of life of family members. Antecedents of depression and anxiety, such as sense of control, may need to be specifically targeted. Our results also suggest that intervention aimed at enhancing social support may be beneficial for family members. RELEVANCE TO CLINICAL PRACTICE: Anxiety and depression did not decrease nor did quality of life improve after the intervention. An educational programme for family members with a component specifically targeting anxiety, depression and quality of life warrants testing. Furthermore, it is important that health care providers understand the influence of social support on anxiety, depression and quality of life when interacting with family members.

Association between use of renin-angiotensin system antagonists and mortality in patients with heart failure and preserved ejection fraction.

CONTEXT: Heart failure with preserved ejection fraction (HFPEF) may be as common and as lethal as heart failure with reduced ejection fraction (HFREF). Three randomized trials of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ie, renin-angiotensin system [RAS] antagonists) did not reach primary end points but may have had selection bias or been underpowered. OBJECTIVE: To test the hypothesis that use of RAS antagonists is associated with reduced all-cause mortality in an unselected population with HFPEF. DESIGN, SETTING, AND PATIENTS: Prospective study using the Swedish Heart Failure Registry of 41,791 unique patients registered from 64 hospitals and 84 outpatient clinics between 2000 and 2011. Of these, 16,216 patients with HFPEF (ejection fraction ≥40%; mean [SD] age, 75 [11] years; 46% women) were either treated (n = 12,543) or not treated (n = 3673) with RAS antagonists. Propensity scores for RAS antagonist use were derived from 43 variables. The association between use of RAS antagonists and all-cause mortality was assessed in a cohort matched 1:1 based on age and propensity score and in the overall cohort with adjustment for propensity score as a continuous covariate. To assess consistency, separate age and propensity score-matched analyses were performed according to RAS antagonist dose in patients with HFPEF and in 20,111 patients with HFREF (ejection fraction <40%) in the same registry. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: In the matched HFPEF cohort, 1-year survival was 77% (95% CI, 75%-78%) for treated patients vs 72% (95% CI, 70%-73%) for untreated patients, with a hazard ratio (HR) of 0.91 (95% CI, 0.85-0.98; P = .008). In the overall HFPEF cohort, crude 1-year survival was 86% (95% CI, 86%-87%) for treated patients vs 69% (95% CI, 68%-71%) for untreated patients, with a propensity score-adjusted HR of 0.90 (95% CI, 0.85-0.96; P = .001). In the HFPEF dose analysis, the HR was 0.85 (95% CI, 0.78-0.83) for 50% or greater of target dose vs no treatment (P < .001) and 0.94 (95% CI, 0.87-1.02) for less than 50% of target dose vs no treatment (P = .14). In the age and propensity score-matched HFREF analysis, the HR was 0.80 (95% CI, 0.74-0.86; P < .001). CONCLUSION: Among patients with heart failure and preserved ejection fraction, the use of RAS antagonists was associated with lower all-cause mortality.

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.

Pre-implant right ventricular function might be an important predictor of the response to cardiac resynchronization therapy.

OBJECTIVE: Cardiac resynchronization therapy is proven efficacious in patients with heart failure (HF). Presence of biventricular HF is associated with a worse prognosis than having only left ventricular (LV) HF and pacing might deteriorate heart function. The aim of the study was to assess a possible significance of right ventricular (RV) pre-implant systolic function to predict response to CRT. DESIGN: We studied 22 HF-patients aged 72 ± 11 years, QRS-duration 155 ± 20 ms and with an LV ejection fraction (EF) of 26 ± 6% before and four weeks after receiving a CRT-device. RESULTS: There were no changes in LV diameters or end systolic volume (ESV) during the study. However, end diastolic volume (EDV) decreased from 226 ± 71 to 211 ± 64 ml (p = 0.02) and systolic maximal velocities (SMV) increased from 2.2 ± 0.4 to 2.6 ± 0.9 cm/s (p = 0.04). Pre-implant RV-SMV (6.2 ± 2.6 cm/s) predicted postoperative increase in LV contractility, p = 0.032. CONCLUSIONS: Pre-implant decreased RV systolic function might be an important way to predict a poor response to CRT implicating that other treatments should be considered. Furthermore we found that 3D- echocardiography and Tissue Doppler Imaging were feasible to detect short-term changes in LV function.

Association of candesartan vs losartan with all-cause mortality in patients with heart failure.

CONTEXT: Angiotensin II receptor blockers (ARBs) reduce combined mortality and hospitalization in patients with heart failure (HF) with reduced left ventricular ejection fraction. Different agents have different affinity for the AT(1) receptor and may have different clinical effects, but have not been tested against each other in HF. OBJECTIVE: To assess the association of candesartan vs losartan with all-cause mortality in patients with HF. DESIGN, SETTING, AND PATIENTS: An HF registry (the Swedish Heart Failure Registry) of 30,254 unique patients registered from 62 hospitals and 60 outpatient clinics between 2000 and 2009. A total of 5139 patients (mean [SD] age, 74 [11] years; 39% women) were treated with candesartan (n = 2639) or losartan (n = 2500). Survival as of December 14, 2009, by ARB agent was analyzed by Kaplan-Meier method and predictors of survival determined by univariate and multivariate proportional hazard regression models, with and without adjustment for propensity scores and interactions. Stratified analyses and quantification of residual confounding were also performed. MAIN OUTCOME MEASURES: All-cause mortality at 1 and 5 years. RESULTS: One-year survival was 90% (95% confidence interval [CI], 89%-91%) for patients receiving candesartan and 83% (95% CI, 81%-84%) for patients receiving losartan, and 5-year survival was 61% (95% CI, 54%-68%) and 44% (95% CI, 41%-48%), respectively (log-rank P < .001). In multivariate analysis with adjustment for propensity scores, the hazard ratio for mortality for losartan compared with candesartan was 1.43 (95% CI, 1.23-1.65; P < .001). The results persisted in stratified analyses. CONCLUSION: In this registry of patients with HF, the use of candesartan compared with losartan was associated with a lower mortality risk.

Sequential biventricular pacing improves regional contractility, longitudinal function and dyssynchrony in patients with heart failure and prolonged QRS.

AIMS: Biventricular pacing (BiP) is an effective treatment in systolic heart failure (HF) patients with prolonged QRS. However, approximately 35% of the patients receiving BiP are classified as non-responders. The aim of this study is to evaluate the acute effects of VV-optimization on systolic heart function. METHODS: Twenty-one HF patients aged 72 (46-88) years, QRS 154 (120-190) ms, were studied with echocardiography, Tissue Doppler Imaging (TDI) and 3D-echo the first day after receiving a BiP device. TDI was performed; during simultaneous pacing (LV-lead pacing 4 ms before the RV-lead) and during sequential pacing (LV 20 and 40 ms before RV and RV 20 and 40 ms before LV-lead pacing). Systolic heart function was studied by tissue tracking (TT) for longitudinal function and systolic maximal velocity (SMV) for regional contractility and signs of dyssynchrony assessed by time-delays standard deviation of aortic valve opening to SMV, AVO-SMV/SD and tissue synchronization imaging (TSI). RESULTS: The TT mean value preoperatively was 4.2 +/- 1.5 and increased at simultaneous pacing to 5.0 +/- 1.2 mm (p < 0.05), and at best VV-interval to 5.4 +/- 1.2 (p < 0.001). Simultaneous pacing achieved better TT distance compared with preoperative in 16 patients (76%). However, it was still higher after VV-optimization in 12 patients 57%. Corresponding figures for SMV were 3.0 +/- 0.7, 3.5 +/- 0.8 (p < 0,01), and 3.6 +/- 0.8 (p < 0.001). Also dyssynchrony improved. CONCLUSIONS: VV-optimization in the acute phase improves systolic heart function more than simultaneous BiP pacing. Long-term effects should be evaluated in prospective randomized trials.

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.

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.

Rationale and design of the Karolinska-Rennes (KaRen) prospective study of dyssynchrony in heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFPEF) is common but not well understood. Electrical dyssynchrony in systolic heart failure is harmful. Little is known about the prevalence and the prognostic impact of dyssynchrony in HFPEF. METHODS AND RESULTS: We have designed a prospective, multicenter, international, observational study to characterize HFPEF and to determine whether electrical or mechanical dyssynchrony affects prognosis. Patients presenting with acute heart failure (HF) will be screened so as to identify 400 patients with HFPEF. Inclusion criteria will be: acute presentation with Framingham criteria for HF, left ventricular ejection fraction>or=45%, brain natriuretic peptide (BNP)>100 pg/mL or NT-proBNP>300 pg/mL. Once stabilized, 4-8 weeks after the index presentation, patients will return and undergo questionnaires, serology, ECG, and Doppler echocardiography. Thereafter, patients will be followed for mortality and HF hospitalization every 6 months for at least 18 months. Sub-studies will focus on echocardiographic changes from the acute presentation to the stable condition and on exercise echocardiography, cardiopulmonary exercise testing, and serological markers. CONCLUSION: KaRen aims to characterize electrical and mechanical dyssynchrony and to assess its prognostic impact in HFPEF. The results might improve our understanding of HFPEF and generate answers to the question whether dyssynchrony could be a target for therapy in HFPEF.

Congestive heart failure with and without atrial fibrillation - different patient populations?

OBJECTIVES: Heart failure (HF) and atrial fibrillation (AF) are common comorbid conditions in hospitalised patients. AF may occur when left ventricular (LV) systolic function deteriorates. The aim was to compare HF patients with AF to patients in sinus rhythm (SR). DESIGN: Echocardiography and a cardiopulmonary exercise test were performed in 67 patients with HF. Peak VO(2) was determined, as were LV-mass, enddiastolic, endsystolic volume indices (EDVI, ESVI), and ejection fraction (EF). RESULTS: EF tended to be higher in AF compared to SR patients (39+/-10 vs. 31+/-10%), LV volume indices were smaller (ESVI:35+/-19 vs. 59+/-25 ml/m(2), p<0.0001, EDVI:56+/-24 vs. 83+/-29 ml/m(2), p<0.001). LV hypertrophy was prevalent (59% vs. 63%) and concentric hypertrophy tended to be more common with AF (50% vs. 21%). Peak VO(2) was similarly reduced in AF and SR (11.4+/-3.2 vs. 12.1+/-4.3 ml/kg*min). CONCLUSIONS: HF patients with AF compared to SR tend to have smaller LV volumes, less compromised systolic function and more frequent LV concentric hypertrophy. Our study supports the concept that AF in HF indicates a different patient population rather than an effect of progressive LV systolic dysfunction.

Prevalence and inter-relationship of different Doppler measures of dyssynchrony in patients with heart failure and prolonged QRS: a report from CARE-HF.

BACKGROUND: Cardiac resynchronisation therapy (CRT) improves mortality and morbidity in heart failure patients with wide QRS. Observational studies suggest that patients having more left ventricular dyssynchrony pre-implantation obtain greater benefit on ventricular function and symptoms with CRT. AIM: To provide an analysis of the prevalence and type of dyssynchrony in patients included in the CARE-HF trial. METHODS: 100 patients 67 (58 to 71) years were examined with echocardiography including tissue doppler imaging before receiving a CRT-pacemaker. Atrio-ventricular dyssynchrony (LVFT/RR) was defined as left ventricular filling time <40% of the RR-interval. Inter-ventricular mechanical delay (IVMD) was measured as the difference in onset of Doppler-flow in the pulmonary and aortic outflow tracts >40 ms. Intra-ventricular (regional) dyssynchrony in a 16-segment model was expressed either as a delayed longitudinal contraction (DLC) during the postsystolic phase or by tissue synchronisation imaging (TSI) with a predefined time-difference in systolic maximal velocities >85 ms. RESULTS: LVFT/RR was present in 34% and IVMD in 60% of patients while intra-ventricular dyssynchrony was present in 85% (DLC) and 86% (TSI) with a high agreement between the measures (Kappascore 0.86-1.00), indicating the methods being interchangeable. Patients with cardiomyopathy (53%) were more likely to have LVFT/RR <40% (45% vs. 21% (p= 0.02)) and more segments affected by intra-ventricular dyssynchrony 4(3, 5) vs. 3(1, 4), p = 0.002, compared to patients with ischemic heart disease. CONCLUSION: The prevalence of intra-ventricular dyssynchrony is high in patients with heart failure, wide QRS and depressed systolic function. Most important, TSI appears to be a fast and reliable method to identify patients with intra-ventricular dyssynchrony likely to benefit from CRT.

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.

Sex differences in systolic heart failure in the elderly: the prognostic importance of left ventricular mass in women.

HYPOTHESIS: We investigated the hypothesis that there are prognostic differences in the importance of left ventricular (LV) mass and function between male and female patients hospitalized with heart failure. METHODS: Patients > or =60 years old hospitalized with New York Heart Association class II-IV heart failure and LV systolic dysfunction were prospectively followed for > or =18 months. At study start, a physical examination and echocardiography were performed, and blood chemistry samples were obtained. RESULTS: Of 158 patients, 66 (42%) women were included and were followed for a mean of 3.1 years. The women were older (77 +/- 7 vs. 74 +/- 7 years, p < 0.01) and had lower mortality (24% vs. 43%, p < 0.05) than the men. No gender differences in etiology or medication were found. LV mass index (LVMI 132 +/- 42 vs. 156 +/- 21 g/m(2), p < 0.01) was lower in women. Mortality in women was related to lower LV ejection fraction, larger LV volumes, and higher LVMI (all p < 0.05). In multivariate analysis, LVMI was the strongest independent mortality predictor in women (adjusted hazard ratio [HR] LMVI >125 g/m(2) 7.4 [1.5-35.5], p = 0.01), whereas this association was not found in men. CONCLUSIONS: In patients hospitalized with systolic heart failure, women had lower mortality than men. In women, an increased LVMI was a stronger predictor of mortality than traditional measures of LV size and function. LVMI should be considered for assessment of prognosis in women with heart failure.