Effect of Tafamidis on Cardiac Function in Patients With Transthyretin Amyloid Cardiomyopathy: A Post Hoc Analysis of the ATTR-ACT Randomized Clinical Trial.

Importance: Tafamidis has been shown to improve survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with placebo. However, its effect on cardiac function has not been fully characterized. Objective: To examine the effect of tafamidis on cardiac function in patients with ATTR-CM. Design, Setting, and Participants: This was an exploratory, post hoc analysis of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), a multicenter, international, double-blind, placebo-controlled phase 3 randomized clinical trial conducted from December 2013 to February 2018. The ATTR-ACT included 48 sites in 13 counties and enrolled patients aged 18 to 90 years with ATTR-CM. Data were analyzed from July 2018 to September 2023. Intervention: Patients were randomized to tafamidis meglumine, 80 mg or 20 mg, or placebo for 30 months. Main Outcomes and Measures: Patients were categorized based on left ventricular (LV) ejection fraction at enrollment as having heart failure with preserved ejection fraction (≥50%), mildly reduced ejection fraction (41% to 49%), or reduced ejection fraction (≤40%). Changes from baseline to month 30 in LV ejection fraction, LV stroke volume, LV global longitudinal strain, and the ratio of early mitral inflow velocity to septal and lateral early diastolic mitral annular velocity (E/e') were compared in patients receiving tafamidis, 80 mg, vs placebo. Results: A total of 441 patients were randomized in ATTR-ACT, and 436 patients had available echocardiographic data. Of 436 included patients, 393 (90.1%) were male, and the mean (SD) age was 74 (7) years. A total of 220 (50.5%), 119 (27.3%), and 97 (22.2%) had heart failure with preserved, mildly reduced, and reduced LV ejection fraction, respectively. Over 30 months, there was less pronounced worsening in 4 of the echocardiographic measures in patients receiving tafamidis, 80 mg (n = 176), vs placebo (n = 177) (least squares mean difference: LV stroke volume, 7.02 mL; 95% CI, 2.55-11.49; P = .002; LV global longitudinal strain, -1.02%; 95% CI, -1.73 to -0.31; P = .005; septal E/e', -3.11; 95% CI, -5.50 to -0.72; P = .01; lateral E/e', -2.35; 95% CI, -4.01 to -0.69; P = .006). Conclusions and Relevance: Compared with placebo, tafamidis, 80 mg, attenuated the decline of LV systolic and diastolic function over 30 months in patients with ATTR-CM. Approximately half of patients had mildly reduced or reduced LV ejection fraction at enrollment, suggesting that ATTR-CM should be considered as a possible diagnosis in patients with heart failure regardless of underlying LV ejection fraction. Trial Registration: ClinicalTrials.gov Identifier: NCT01994889.

Characteristics and management of very elderly patients with heart failure: a retrospective, population cohort study.

AIMS: Unmet needs exist in the diagnosis and treatment of heart failure (HF) in the elderly population. Our aim was to analyse and compare data of diagnostics and management of very elderly patients (aged ≥85 years) compared with younger patients (aged 18-84 years) with HF in Sweden. METHODS: Incidence of ≥2 HF diagnosis (ICD-10) was identified from primary/secondary care in Uppsala and Västerbotten during 2010-2015 via electronic medical records linked to data from national health registers. Analyses investigated the diagnosis, treatment patterns, hospitalizations and outpatient visits, and mortality. RESULTS: Of 8702 patients, 27.7% were ≥85 years old, women (60.2%); most patients (80.7%) had unknown left ventricular ejection fraction; key co-morbidities comprised anaemia, dementia, and cerebrovascular disease. More very elderly patients received cardiovascular disease (CVD)-related management after diagnosis in primary care (13.6% vs. 6.5%; P < 0.0001), but fewer patients underwent echocardiography (19.3% vs. 42.9%; P < 0.0001). Within 1 year of diagnosis, very elderly patients were less likely to be hospitalized (all-cause admissions per patient: 1.9 vs. 2.3; P < 0.0001; CVD-related admissions per patient: 1.8 vs. 2.1; P = 0.0004) or prescribed an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) plus a ß-blocker (45.2% vs. 56.9%; P < 0.0001) or an ACEI/ARB plus a ß-blocker plus a mineralocorticoid receptor antagonist (15.4% vs. 31.7%; P < 0.0001). One-year mortality was high in patients ≥85 years old, 30.5% (CI: 28.3-32.7%) out of 1797 patients. CONCLUSIONS: Despite the large number of very elderly patients with newly diagnosed HF in Sweden, poor diagnostic work-up and subsequent treatment highlight the inequality of care in this vulnerable population.

Healthcare resource utilisation and costs associated with a heart failure diagnosis: a retrospective, population-based cohort study in Sweden.

OBJECTIVES: To examine healthcare resource use (HRU) and costs among heart failure (HF) patients using population data from Sweden. DESIGN: Retrospective, non-interventional cohort study. SETTING: Two cohorts were identified from linked national health registers (cohort 1, 2005-2014) and electronic medical records (cohort 2, 2010-2012; primary/secondary care patients from Uppsala and Västerbotten). PARTICIPANTS: Patients (aged ≥18 years) with primary or secondary diagnoses of HF (≥2 International Classification of Diseases and Related Health Problems, 10th revision classification) during the identification period of January 2005 to March 2015 were included. OUTCOME MEASURES: HRU across the HF phenotypes was assessed with logistic regression. Costs were estimated based on diagnosis-related group codes and general price lists. RESULTS: Total annual costs of secondary care of prevalent HF increased from SEK 6.23 (€0.60) to 8.86 (€0.85) billion between 2005 and 2014. Of 4648 incident patients, HF phenotype was known for 1715: reduced ejection fraction (HFrEF): 64.5%, preserved ejection fraction (HFpEF): 35.5%. Within 1 year of HF diagnosis, the proportion of patients hospitalised was only marginally higher for HFrEF versus HFpEF (all-cause (95% CI): 64.7% (60.8 to 68.4) vs 63.7% (60.8 to 66.5), HR 0.91, p=0.14; cardiovascular disease related (95% CI): 61.1% (57.1 to 64.8) vs 60.9% (58.0 to 63.7), HR 0.93, p=0.28). Frequency of hospitalisations and outpatient visits per patient declined after the first year. All-cause secondary care costs in the first year were SEK 122 758 (€12 890)/patient/year, with HF-specific care accounting for 69% of the costs. Overall, 10% of the most expensive population (younger; predominantly male; more likely to have comorbidities) incurred ~40% of total secondary care costs. CONCLUSIONS: HF-associated costs and HRU are high, especially during the first year of diagnosis. This is driven by high hospitalisations rates. Understanding the profile of resource-intensive patients being at younger age, male sex and high Charlson comorbidity index scores at the time of the HF diagnosis is most likely a sign of more severe disease.

Recurrent heart failure hospitalizations increase the risk of cardiovascular and all-cause mortality in patients with heart failure in Sweden: a real-world study.

AIMS: Heart failure (HF) is a leading cause of hospitalization and is associated with high morbidity and mortality. We examined the impact of recurrent HF hospitalizations (HFHs) on cardiovascular (CV) mortality among patients with HF in Sweden. METHODS AND RESULTS: Adults with incident HF were identified from linked national health registers and electronic medical records from 01 January 2005 to 31 December 2013 for Uppsala and until 31 December 2014 for Västerbotten. CV mortality and all-cause mortality were evaluated. A time-dependent Cox regression model was used to estimate relative CV mortality rates for recurrent HFHs. Assessment was also done for ejection fraction-based HF phenotypes and for comorbid atrial fibrillation, diabetes, or chronic renal impairment. Overall, 3878 patients with HF having an index hospitalization were included, providing 9691.9 patient-years of follow-up. Patients were relatively old (median age: 80 years) and were more frequently male (55.5%). Compared with patients without recurrent HFHs, the adjusted hazard ratio (HR [95% confidence interval; CI]) for CV mortality and all-cause mortality were statistically significant for patients with one, two, three, and four or more recurrent HFHs. The risk of CV mortality and all-cause mortality increased approximately six-fold in patients with four or more recurrent HFHs vs. those without any HFHs (HR [95% CI]: 6.26 [5.24-7.48] and 5.59 [4.70-6.64], respectively). Similar patterns were observed across the HF phenotypes and patients with comorbidities. CONCLUSIONS: There is a strong association between recurrent HFHs and CV and all-cause mortality, with the risk increasing progressively with each recurrent HFH.

Clinical profile of rural community hospital inpatients in Sweden - a register study.

OBJECTIVE: Patients in Sweden's rural community hospitals have not been clinically characterised. We compared characteristics of patients in general practitioner-led community hospitals in northern Sweden with those admitted to general hospitals. DESIGN: Retrospective register study. SETTING: Community and general hospitals in Västerbotten and Norrbotten counties, Sweden. PATIENTS: Patients enrolled at community hospitals and hospitalised in community and general hospitals between 1 January 2010 and 31 December 2014. OUTCOME MEASURES: Age, sex, number of admissions, main, secondary and total number of diagnoses. RESULTS: We recorded 16,133 admissions to community hospitals and 60,704 admissions to general hospitals. Mean age was 76.8 and 61.2 years for community and general hospital patients (p < .001). Women were more likely than men to be admitted to a community hospital after age adjustment (odds ratio (OR): 1.11; 95% confidence interval (CI): 1.09-1.17). The most common diagnoses in community hospital were heart failure (6%) and pneumonia (5%). Patients with these diagnoses were more likely to be admitted to a community than a general hospital (OR: 2.36; 95% CI: 2.15-2.59; vs. OR: 3.32: 95% CI: 2.77-3.98, respectively, adjusted for age and sex). In both community and general hospitals, doctors assigned more diagnoses to men than to women (both p<.001). CONCLUSIONS: Patients at community hospitals were predominantly older and women, while men were assigned more diagnoses. The most common diagnoses were heart failure and pneumonia. Our observed differences should be further explored to define the optimal care for patients in community and general hospitals.Key pointsThe patient characteristics at Swedish general practitioner-led rural community hospitals have not yet been reported. This study characterises inpatients in community hospitals compared to those referred to general hospitals.• Patients at community hospitals were predominantly older, with various medical conditions that would have led to a referral to general hospitals elsewhere in Sweden. • Compared to men, women were more likely to be admitted to community hospitals than to general hospitals, even after adjustment for age. To the best of our knowledge, this pattern has not been reported in other countries with community hospitals. • In both community hospitals and general hospitals, doctors assigned more diagnoses to men than to women.

Efficacy of Tafamidis in Patients With Hereditary and Wild-Type Transthyretin Amyloid Cardiomyopathy: Further Analyses From ATTR-ACT.

OBJECTIVES: Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), this study aimed to determine whether there is a differential effect between variant transthyretin amyloidosis (ATTRv) and wild-type transthyretin (ATTRwt). BACKGROUND: ATTR-CM is a progressive, fatal disorder resulting from mutations in the ATTRv or the deposition of denatured ATTRwt. METHODS: In pre-specified analyses from ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial), baseline characteristics, all-cause mortality, and change from baseline to month 30 in 6-min walk test distance and Kansas City Cardiomyopathy Questionnaire Overall Summary score were compared in patients with ATTRwt and ATTRv. RESULTS: There were 335 patients with ATTRwt (201 tafamidis, 134 placebo) and 106 with ATTRv (63 tafamidis, 43 placebo) enrolled in ATTR-ACT. Patients with ATTRwt (vs. ATTRv) had less advanced disease at baseline and a lower rate of disease progression over the study. The reduction in all-cause mortality with tafamidis compared with placebo was not different between ATTRwt (hazard ratio: 0.706 [95% confidence interval (CI): 0.474 to 1.052]; p = 0.0875) and ATTRv (hazard ratio: 0.690 [95% CI: 0.408 to 1.167]; p = 0.1667). Tafamidis was associated with a similar reduction (vs. placebo) in the decline in 6-min walk test distance in ATTRwt (mean ± SE difference from placebo, 77.14 ± 10.78; p < 0.0001) and ATTRv (79.61 ± 29.83 m; p = 0.008); and Kansas City Cardiomyopathy Questionnaire Overall Summary score in ATTRwt (12.72 ± 2.10; p < 0.0001) and ATTRv (18.18 ± 7.75; p = 0.019). CONCLUSIONS: Pre-specified analyses from ATTR-ACT confirm the poor prognosis of untreated ATTRv-related cardiomyopathy compared with ATTRwt, but show the reduction in mortality and functional decline with tafamidis treatment is similar in both disease subtypes. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT]; NCT01994889).

Leptin levels are not affected by enalapril treatment after an uncomplicated myocardial infarction, but associate strongly with changes in fibrinolytic variables in men.

Leptin, an adipocyte-derived hormone, is involved in the regulation of body weight and is associated with obesity-related complications, notably cardiovascular disease (CVD). A putative link between obesity and CVD could be induction of plasminogen activator inhibitor-1 (PAI-1) synthesis by leptin. In this study, we hypothesized that the beneficial effect of the angiotensin-converting enzyme inhibitor (ACEi) enalapril on PAI-1 levels is mediated by effects on leptin levels. The association between leptin and components of the fibrinolytic system was evaluated in a non-prespecified post hoc analysis of a placebo-controlled randomized, double-blind trial where the effect of the ACEi enalapril on fibrinolysis was tested. A total of 46 men and 37 women were randomized to treatment with enalapril or placebo after (median 12 months) an uncomplicated myocardial infarction. At baseline, the participants were stable and had no signs of congestive heart failure. Leptin and fibrinolytic variables (mass concentrations of PAI-1, tissue plasminogen activator (tPA) and tPA-PAI complex) were measured at baseline, and after 10 days, 6 months and 12 months. Enalapril treatment did not change leptin levels, which increased significantly during 1 year of follow-up (p = .007). Changes in leptin levels were strongly associated with changes of tPA mass (p = .001), tPA-PAI complex (p = .003) and of PAI-1 (p = .006) in men, but not in women. Leptin levels are not influenced by treatment with an ACEi. In contrast, leptin associates strongly with changes in fibrinolytic variables notably with a sex difference, which could be of importance for obesity-related CVD.

Patients' experiences of person-centred integrated heart failure care and palliative care at home: an interview study.

OBJECTIVES: Patients with severe heart failure (HF) suffer from a high symptom burden and high mortality. European and Swedish guidelines for HF care recommend palliative care for these patients. Different models for integrated palliative care and HF care have been described in the literature. No studies were found that qualitatively evaluated these models. The purpose of this study is to describe patients' experiences of a new model of person-centred integrated HF and palliative care at home. METHOD: Interviews were conducted with 12 patients with severe HF (New York Heart Association class IIIâ€"IV) and included in the research project of Palliative advanced home caRE and heart FailurE caRe (PREFER). Qualitative content analysis was used for data analysis. RESULTS: Two themes and a total of five categories were identified. The first theme was feeling secure and safe through receiving care at home with the categories: having access to readily available care at home, being followed up continuously and having trust in the team members' ability to help. The second theme was being acknowledged as both a person and a patient, with the following two categories: being met as a person, participating in decisions about one's care and receiving help for symptoms of both HF and comorbidities. CONCLUSIONS: Person-centred integrated HF and palliative care provides a secure environment and holistic care for patients with severe HF. This approach is a way to improve the care management in this population. TRIAL REGISTRATION NUMBER: NCT01304381; Results.

Relation of Lipid-Lowering Therapy to Need for Aortic Valve Replacement in Patients With Asymptomatic Mild to Moderate Aortic Stenosis.

In this study, we aimed to determine if pretreatment low-density lipoprotein (LDL) levels and aortic stenosis (AS) severity alter the efficacy of lipid-lowering therapy on reducing aortic valve replacement (AVR). We used 1,687 patients with asymptomatic mild-to-moderate AS, who were randomly assigned (1:1) to 40/10 mg simvastatin/ezetimibe combination versus. placebo in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial. Pretreatment LDL levels (>4 mmol/L) and peak aortic jet velocity (3 m/s) were used to partition study participants into 4 groups, which were followed for a primary endpoint of AVR. Cox regression with tests for interaction was used to study the effect of randomized treatment in each subgroup. During a median follow-up of 4.3 years (IQR 4.2 to 4.7 years; total 7,396 patient-years of follow-up), 478 (28%) patients underwent AVR and 146 (9%) died. A significant risk dependency was detected between simvastatin/ezetimibe combination, LDL levels and mild versus moderate AS on rates of AVR (p = 0.01 for interaction). In stratified analyses, randomized treatment, therefore, reduced the rate of AVR in patients with LDL levels >4 mmol and mild AS at baseline (HR 0.4; 95% CI: 0.2 to 0.9). There was no detectable effect of randomized treatment on the need for AVR in the 3 other participants subgroups. We conclude, that in a secondary analysis from a prospective randomized clinical trial, treatment with simvastatin/ezetimibe combination reduced the need for AVR in a subset of patients with mild AS and high pretreatment LDL levels (Unique identifier on clinicaltrials.gov: NCT00092677).

Flawed conclusions on the Västerbotten Intervention Program by San Sebastian et .al.

An evaluation of Västerbotten Intervention Programme (VIP) was recently conducted by San Sebastian et al. (BMC Public Health 19:202, 2019). Evaluation of health care interventions of this kind require 1) an understanding of both the design and the nature of the intervention, 2) correct definition of the target population, and 3) careful choice of the appropriate evaluation method. In this correspondence, we review the approach used by San Sebastian et al. as relates to these three criteria. Within this framework, we suggest important explanations for why the conclusions drawn by these authors contradict a large body of research on the effectiveness of the VIP.

Epidemiology of heart failure and trends in diagnostic work-up: a retrospective, population-based cohort study in Sweden.

PURPOSE: The purpose of this study was to examine the trends in heart failure (HF) epidemiology and diagnostic work-up in Sweden. METHODS: Adults with incident HF (≥2 ICD-10 diagnostic codes) were identified from linked national health registers (cohort 1, 2005-2013) and electronic medical records (cohort 2, 2010-2015; primary/secondary care patients from Uppsala and Västerbotten). Trends in annual HF incidence rate and prevalence, risk of all-cause and cardiovascular disease (CVD)-related 1-year mortality and use of diagnostic tests 6 months before and after first HF diagnosis (cohort 2) were assessed. RESULTS: Baseline demographic and clinical characteristics were similar for cohort 1 (N=174,537) and 2 (N=8,702), with mean ages of 77.4 and 76.6 years, respectively; almost 30% of patients were aged ≥85 years. From 2010 to 2014, age-adjusted annual incidence rate of HF/1,000 inhabitants decreased (from 3.20 to 2.91, cohort 1; from 4.34 to 3.33, cohort 2), while age-adjusted prevalence increased (from 1.61% to 1.72% and from 2.15% to 2.18%, respectively). Age-adjusted 1-year all-cause and CVD-related mortality was higher in men than in women among patients in cohort 1 (all-cause mortality hazard ratio [HR] men vs women 1.07 [95% CI 1.06-1.09] and CVD-related mortality subdistribution HR for men vs women 1.04 [95% CI 1.02-1.07], respectively). While 83.5% of patients underwent N-terminal pro-B-type natriuretic peptide testing, only 36.4% of patients had an echocardiogram at the time of diagnosis, although this increased overtime. In the national prevalent HF population (patients with a diagnosis in 1997-2004 who survived into the analysis period; N=273,999), death from ischemic heart disease and myocardial infarction declined between 2005 and 2013, while death from HF and atrial fibrillation/flutter increased (P<0.0001 for trends over time). CONCLUSION: The annual incidence rate of HF declined over time, while prevalence of HF has increased, suggesting that patients with HF were surviving longer over time. Our study confirms that previously reported epidemiological trends persist and remain to ensure proper diagnostic evaluation and management of patients with HF.

Testosterone, sex hormone-binding globulin and risk of cardiovascular events: A report from the Outcome Reduction with an Initial Glargine Intervention trial.

AIMS: Testosterone and its binding protein sex hormone-binding globulin have been associated with cardiovascular disease and dysglycaemia. However, information on the prognostic implication in patients at high cardiovascular risk with dysglycaemia is inconsistent. The study objective was to determine whether testosterone and/or sex hormone-binding globulin predict cardiovascular events or death in dysglycaemic patients. METHODS: Dysglycaemic males at high cardiovascular risk ( n = 5553) who participated in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial and provided baseline blood samples were studied. Testosterone and sex hormone-binding globulin were measured at baseline and used to estimate free testosterone. Low levels of total and free testosterone were defined as ≤300 ng/dl and ≤7 ng/dl, respectively. Patients were followed for six years for cardiovascular events (defined as the composite of cardiovascular death, non-fatal myocardial infarction or stroke) and all-cause mortality. RESULTS: The mean total and free testosterone levels were 416.6 ng/dl and 8.4 ng/dl, and low levels were present in 13% and 37% of the patients. The median sex hormone-binding globulin level was 35 nmol/l. In Cox regression models adjusted for age, previous diseases and pharmacological treatment, neither total nor free testosterone predicted cardiovascular events. However, a one-standard-deviation increase in sex hormone-binding globulin predicted both cardiovascular events (hazard ratio 1.07; 95% confidence interval 1.00-1.14; p = 0.03) and all-cause mortality (hazard ratio 1.13; 95% confidence interval 1.06-1.21; p < 0.01). CONCLUSION: Sex hormone-binding globulin, but not total testosterone, predicts cardiovascular disease and all-cause mortality in dysglycaemic males at high cardiovascular risk.

Impacts of person-centred integrated chronic heart failure and palliative home care on pharmacological heart failure treatment: a substudy of a randomised trial.

OBJECTIVE: Patients with chronic heart failure (CHF) may be insufficiently treated pharmacologically. Recently, we presented a person-centred integrated Palliative advanced homecaRE and heart FailurE caRe (PREFER) strategy and compared it with usual care (control). Patients managed according to PREFER had improved health-related quality of life and markedly reduced hospitalisations compared with the control group. We hypothesised that these improvements may have been partly due to better drug treatments within the PREFER strategy. Thus, our aim in this study was to explore the management of drug treatments in the PREFER group compared with the control group. METHODS: Doses and numbers of drugs and the number of patients receiving the target doses based on current guidelines were measured and compared between the groups at the start and finish of the study. RESULTS: The percentages of ACE inhibitors (ACEIs) or mineralocorticoid receptor antagonists (MRAs) increased, while loop diuretics decreased in the PREFER arm during the study, although the differences were not significant. Beta-receptor blockers (BBs) decreased somewhat in both groups. The number of patients treated with MRAs differed the most between groups, and increased from 10 (28%) to 15 (48%) in the PREFER arm compared with 13 (35%) vs 13 (39%) in the control group. The change in patients receiving full target doses (+8 vs. +1) of the ACEIs/angiotensin receptor blockers, BBs and MRAs were significantly higher (p=0009) in the PREFER arm than in the control arm. CONCLUSIONS: Person-centred integrated care of patients with severe CHF was associated with increased evidence-based drug treatments, especially MRAs. CLINICAL TRIAL NUMBER: NCT01304381.

Effect of simvastatin and ezetimibe on suPAR levels and outcomes.

BACKGROUND AND AIMS: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown. METHODS: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model. A 1-year Cox analysis, adjusted for established cardiovascular risk factors, allocation to study treatment, peak aortic valve velocity and baseline suPAR, was performed to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE). RESULTS: After 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%-11.5%) in the placebo group, but only by 4.1% (1.9%-6.2%) in the group with lipid-lowering treatment (p<0.001). In a multivariate 1-year analysis, 1-year suPAR was strongly associated with all-cause mortality, hazard ratio (HR) = 2.05 (1.17-3.61); MCE 1.40 (1.01-1.92); and AVE 1.42 (1.02-1.99) (all p<0.042) for each doubling of suPAR; but was not associated with ICE. CONCLUSIONS: Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677).

A mixed methods study of Tai Chi exercise for patients with chronic heart failure aged 70 years and older.

Aims and objectives: This study aimed to evaluate Tai Chi group training among patients with chronic heart failure (CHF) aged 70 years and older. Background: Physical activity is recommended for CHF treatment. Tai Chi is found to be beneficial to different patient groups, although few studies focus on older patients with CHF. Design: A mixed methods study. Participants were randomly assigned to Tai Chi training twice a week for 16 weeks (N = 25) or control (N = 20). Quantitative data were collected at baseline, at the end of the training period and 6 months after training, assessing self-rated fatigue and quality of life, natriuretic peptides and physical performance. Individual qualitative interviews were conducted with participants (N = 10) in the Tai Chi training group. Results: No statistical differences between the Tai Chi training group and the control group in quality of life or natriuretic peptides was found. After 16 weeks, the training group tended to rate more reduced activity and the control group rated more mental fatigue. Participants in the training group rated increased general fatigue at follow-up compared with baseline. Qualitative interviews showed that Tai Chi training was experienced as a new, feasible and meaningful activity. The importance of the leader and the group was emphasized. Improvements in balance were mentioned and there was no physical discomfort. Conclusion: Tai Chi was experienced as a feasible and meaningful form of physical exercise for patients with CHF aged over 70 years despite lack of achieved health improvement. Further investigations, using feasibility and meaningfulness as outcome variables seems to be useful.

SuPAR predicts postoperative complications and mortality in patients with asymptomatic aortic stenosis.

Background: We evaluated whether early measurement of soluble urokinase plasminogen activator receptor (suPAR) could predict future risk of postoperative complications in initially asymptomatic patients with mild-moderate aortic stenosis (AS) undergoing aortic valve replacement (AVR) surgery. Methods: Baseline plasma suPAR levels were available in 411 patients who underwent AVR surgery during follow-up in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox analyses were used to evaluate suPAR in relation to all-cause mortality and the composite endpoint of postoperative complications (all-cause mortality, congestive heart failure, stroke and renal impairment) occurring in the 30-day postoperative period. Results: Patients with initially higher levels of suPAR were at increased risk of postoperative mortality with a HR of 3.5 (95% CI 1.4 to 9.0, P=0.008) and postoperative complications with a HR of 2.7 (95% CI 1.5 to 5.1, P=0.002), per doubling in suPAR. After adjusting for the European System for Cardiac Operative Risk Evaluation or Society of Thoracic Surgeons risk score, suPAR remained associated with postoperative mortality with a HR 3.2 (95% CI 1.2 to 8.6, P=0.025) and 2.7 (95% CI 1.0 to 7.8, P=0.061); and postoperative complications with a HR of 2.5 (95% CI 1.3 to 5.0, P=0.007) and 2.4 (95% CI 1.2 to 4.8, P=0.011), respectively. Conclusion: Higher baseline suPAR levels are associated with an increased risk for postoperative complications and mortality in patients with mild-moderate, asymptomatic AS undergoing later AVR surgery. Further validation in other subsets of AS individuals are warranted. Trial registration number: NCT00092677; Post-results.

Effect Modifications of Lipid-Lowering Therapy on Progression of Aortic Stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis [SEAS] Study).

Observational studies indicate that low-density lipoprotein (LDL) cholesterol acts as a primary contributor to an active process leading to aortic stenosis (AS) development. However, randomized clinical trials have failed to demonstrate an effect of lipid lowering on impeding AS progression. This study explored if pretreatment LDL levels and AS severity altered the efficacy of lipid-lowering therapy. The study goal was evaluated in the analysis of surviving patients with baseline data in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of 1,873 asymptomatic patients with mild-to-moderate AS. Serially measured peak aortic jet velocity was the primary effect estimate. Linear mixed model analysis adjusted by baseline peak jet velocity and pretreatment LDL levels was used to assess effect modifications of treatment. Data were available in 1,579 (84%) patients. In adjusted analyses, lower baseline peak aortic jet velocity and higher pretreatment LDL levels increased the effect of randomized treatment (p = 0.04 for interaction). As such, treatment impeded progression of AS in the highest quartile of LDL among patients with mild AS at baseline (0.06 m/s per year slower progression vs placebo in peak aortic jet velocity, 95% confidence interval 0.01 to 0.11, p = 0.03), but not in the 3 other quartiles of LDL. Conversely, among patients with moderate AS, there was no detectable effect of treatment in any of the pretreatment LDL quartiles (all p ≥0.14). In conclusion, in a non-prespecified post hoc analysis, the efficacy of lipid-lowering therapy on impeding AS progression increased with higher pretreatment LDL and lower peak aortic jet velocity (SEAS study: NCT00092677).

NTproBNP and ST2 as predictors for all-cause and cardiovascular mortality in elderly patients with symptoms suggestive for heart failure.

BACKGROUND: A new biomarker, suppression of tumorigenicity 2 (ST2) has been introduced as a marker for fibrosis and hypertrophy. Its clinical value in comparison with N-terminal pro-hormone of brain natriuretic peptide /Amino-terminal pro-B-type natriuretic peptide (NTproBNP) in predicting mortality in elderly patients with symptoms of heart failure (HF) is still unclear. AIM: To evaluate the prognostic value for all-cause- and cardiovascular mortality of ST2 or NTproBNP and the combination of these biomarkers. PATIENTS AND METHODS: One hundred seventy patients patients with clinical symptoms of HF (77 (45%) were with verified HF) were recruited from one selected primary health care center (PHC) in Sweden and echocardiography was performed in all patients. Blood samples were obtained from 159 patients and stored frozen at -70 °C. NTproBNP was analyzed at a central core laboratory using a clinically available immunoassay.ST2 was analyzed with Critical Diagnostics Presage ST2 ELISA immunoassay. RESULTS: We studied 159 patients (mean age 77 ± 8.3 years, 70% women). During ten years of follow up 78 patients had died, out of which 50 deaths were for cardiovascular reasons. Continuous NTproBNP and ST2 were both significantly associated with all-cause mortality (1.0001; 1.00001-1.0002, p = 0.04 and 1.03; 1.003-1.06, p = 0.03), NTproBNP but not ST2 remained significant for cardiovascular mortality after adjustments (1.0001; 1.00001-1.0002, p = 0.03 and 1.01; 0.77-1.06, p = 0.53), respectively. NTproBNP above median (>328 ng/L) compared to below median was significantly associated with all-cause mortality(HR: 4.0; CI :2.46-6.61; p < 0.001) and cardiovascular mortality (HR: 6.1; CI: 3.11-11.95; p < 0.001). Corresponding analysis for ST2 above median (25.6 ng/L) was not significantly associated neither with all-cause mortality (HR; 1.4; CI: 0.89-2.77) nor cardiovascular mortality (HR: 1.3; CI: 0.73-2.23) and no significant interaction of NTproBNP and ST2 (OR: 1.1; CI: 0.42-3.12) was found. CONCLUSION: In elderly patients with symptoms of heart failure ST2 was not superior to NTproBNP to predict all cause or cardiovascular mortality. Furthermore, it is unclear if the combination of ST2 and NTproBNP will improve long-term prognostication beyond what is achieved by NTproBNP alone.

Symptom Relief and Palliative Care during the Last Week of Life among Patients with Heart Failure: A National Register Study.

BACKGROUND: Heart failure is a disease with high morbidity, mortality, and physical and psychological burden. More knowledge about the care provided for patients with heart failure close to death is needed. OBJECTIVE: The aim was to describe key aspects of palliative care during the last week of life in patients with heart failure, as reported by healthcare professionals. DESIGN: This is a national register study. SETTING/SUBJECTS: The study included 3981 patients with diagnosed heart failure as the underlying cause of death. MEASUREMENTS: Data were obtained from the Swedish Register of Palliative Care, a national quality register that focuses on patients' last week of life, independent of diagnosis or care setting. The register includes information about care interventions connected with key aspects of palliative care. Data are reported retrospectively by a nurse or physician at the healthcare unit where the patient dies. RESULTS: Only 4.2% of patients with heart failure received specialized palliative care. In their last week of life, symptom prevalence was high, validated scales were seldom used, and symptoms were unsatisfactorily relieved. Around one-fifth (17%) of the patients in the study died alone. Less than half of family members had been offered bereavement support (45%). Moreover, one-third (28%) of the patients and more than half (61%) of the family members were reported to have had end-of-life discussions with a physician during the illness trajectory. CONCLUSION: The results indicate inadequate palliative care for patients with heart failure during their last week of life.

Family members' experiences of integrated palliative advanced home and heart failure care: A qualitative study of the PREFER intervention.

ABSTRACTObjective:Chronic heart failure is a disease with high morbidity and symptom burden for patients, and it also places great demands on family members. Patients with heart failure should have access to palliative care for the purpose of improving quality of life for both patients and their families. In the PREFER randomized controlled intervention, patients with New York Heart Association classes III-IV heart failure received person-centered care with a multidisciplinary approach involving collaboration between specialists in palliative and heart failure care. The aim of the present study was to describe family members' experiences of the intervention, which integrated palliative advanced home and heart failure care. METHOD: This study had a qualitative descriptive design based on family member interviews. Altogether, 14 family members participated in semistructured interviews for evaluation after intervention completion. The data were analyzed by means of content analysis. RESULTS: Family members expressed gratitude and happiness after witnessing the patient feeling better due to symptom relief and empowerment. They also felt relieved and less worried, as they were reassured that the patient was being cared for properly and that their own responsibility for care was shared with healthcare professionals. However, some family members also felt as though they were living in the shadow of severe illness, without receiving any support for themselves. SIGNIFICANCE OF RESULTS: Several benefits were found for family members from the PREFER intervention, and our results indicate the significance of integrated palliative advanced home and heart failure care. However, in order to improve this intervention, psychosocial professionals should be included on the intervention team and should contribute by paying closer attention and providing targeted support for family members.