Search

Aims Although body mass index (BMI) is the most commonly used anthropometric measure, newer indices such as the waist-to-height ratio, better reflect the location and amount of ectopic fat, as well as the weight of the skeleton, and may be more useful. Methods and results The prognostic value of several newer anthropometric indices was compared with that of BMI in patients with heart failure (HF) and reduced ejection fraction (HFrEF) enrolled in prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure. The primary outcome was HF hospitalization or cardiovascular death. The association between anthropometric indices and outcomes were comprehensively adjusted for other prognostic variables, including natriuretic peptides. An ‘obesity-survival paradox’ related to lower mortality risk in those with BMI ≥25 kg/m2 (compared with normal weight) was identified but this was eliminated by adjustment for other prognostic variables. This paradox was less evident for waist-to-height ratio (as an exemplar of indices not incorporating weight) and eliminated by adjustment: the adjusted hazard ratio (aHR) for all-cause mortality, for quintile 5 vs. quintile 1, was 1.10 [95% confidence interval (CI) 0.87–1.39]. However, both BMI and waist-to-height ratio showed that greater adiposity was associated with a higher risk of the primary outcome and HF hospitalization; this was more evident for waist-to-height ratio and persisted after adjustment e.g. the aHR for HF hospitalization for quintile 5 vs. quintile 1 of waist-to-height ratio was 1.39 (95% CI 1.06–1.81). Conclusion In patients with HFrEF, alternative anthropometric measurements showed no evidence for an ‘obesity-survival paradox’. Newer indices that do not incorporate weight showed that greater adiposity was clearly associated with a higher risk of HF hospitalization.

Up to 20% of patients in heart failure with reduced ejection fraction (HFrEF) trials are not taking diuretic agents at baseline, but little is known about them.The aim of this study was to examine outcomes in patients with HFrEF not taking diuretic medications and after diuretic medications are started.Patient characteristics and outcomes were compared between patients taking or not taking diuretic drugs at baseline in the ATMOSPHERE (Aliskiren Trial of Minimizing Outcomes for Patients With Heart Failure) and PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) trials combined. Patients starting diuretic medications were also compared with those remaining off diuretic drugs during follow-up. Symptoms (Kansas City Cardiomyopathy Questionnaire Clinical Summary Score [KCCQ-CSS]), hospitalization for worsening heart failure (HF), mortality, and kidney function (estimated glomerular filtration rate slope) were examined.At baseline, the 3,079 of 15,415 patients (20%) not taking diuretic medications had a less severe HF profile, less neurohumoral activation, and better kidney function. They were less likely to experience the primary outcome (hospitalization for HF or cardiovascular death) than patients taking diuretic agents (adjusted HR: 0.77; 95% CI: 0.74-0.80; P 0.001) and death of any cause. Commencement of a diuretic drug was associated with higher subsequent risk for death (adjusted HR: 2.05; 95% CI: 1.99-2.11; P 0.001) and greater decreases in KCCQ-CSS and estimated glomerular filtration rate. The 5 strongest predictors of initiation of diuretic medications were higher N-terminal pro-B-type natriuretic peptide, higher body mass index, older age, history of diabetes, and worse KCCQ-CSS. In PARADIGM-HF, fewer patients who were treated with sacubitril/valsartan commenced diuretic agents (OR: 0.72; 95% CI: 0.58-0.88; P = 0.002).Patients with HFrEF not taking diuretic medications and those who remained off them had better outcomes than patients treated with diuretic agents or who commenced them.

Aims The 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation combining creatinine and cystatin C provides a better estimation of glomerular filtration rate (GFR) compared to the creatinine-only equation. Methods and results CKD-EPI creatinine-cystatin C equation (creatinine-cystatin) was compared to creatinine-only (creatinine) equation in a subpopulation of Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF). Patients were categorized according to difference in eGFR using the two equations: Group 1 (−10 and 10 mL/min/1.73 m2, i.e. creatinine-cystatin more than 10 mL/min higher than creatinine). Cystatin C and creatinine were available in 1966 patients at randomization. Median (interquartile range) eGFR difference was −0.7 (−6.4–4.8) mL/min/1.73 m2. Compared to creatinine, creatinine-cystatin led to a substantial reclassification of chronic kidney disease stages. Overall, 212 (11%) and 355 (18%) patients were reallocated to a better and worse eGFR category, respectively. Compared to patients in Group 2, those in Group 1 (lower eGFR with creatinine-cystatin) had higher mortality and those in Group 3 (higher eGFR with creatinine-cystatin) had lower mortality. Increasing difference in eGFR (due to lower eGFR with creatinine-cystatin compared to creatinine) was associated with increasing elevation of biomarkers (including N-terminal pro-B-type natriuretic peptide and troponin) and worsening Kansas City Cardiomyopathy Questionnaire clinical summary score. The reason why the equations diverged with increasing severity of heart failure was that creatinine did not rise as steeply as cystatin C. Conclusion The CKD-EPI creatinine-only equation may overestimate GFR in sicker patients. Clinical Trial Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01035255.

Heart failure with reduced ejection fraction (HFrEF) and chronic obstructive pulmonary disease (COPD) individually cause significant morbidity and mortality. Their coexistence is associated with even worse outcomes, partly due to suboptimal heart failure therapy, especially underutilisation of beta-blockers. Our aim was to investigate outcomes in HFrEF patients with and without COPD, and the effects of mineralocorticoid receptor antagonists (MRAs) on outcomes.\ud \ud Methods and results:\ud \ud We studied the effect of MRA therapy in a post-hoc pooled analysis of 4397 HFrEF patients in the RALES and EMPHASIS-HF trials. The primary endpoint was the composite of heart failure hospitalisation or cardiovascular death. A total of 625 (14.2%) of the 4397 patients had COPD. Patients with COPD were older, more often male, and smokers, but less frequently treated with a beta-blocker. In patients with COPD, event rates (per 100 person-years) for the primary endpoint and for all-cause mortality were 25.2 (95% confidence interval 22.1–28.7) and 17.2 (14.9–19.9), respectively, compared with 19.9 (18.8–21.1) and 12.8 (12.0–13.7) in participants without COPD. The risks of all-cause hospitalisation and sudden death were also higher in patients with COPD. The benefit of MRA, compared with placebo, was consistent in patients with or without COPD for all outcomes, e.g. hazard ratio for the primary outcome 0.66 (0.50–0.85) for COPD and 0.65 (0.58–0.73) for no COPD (interaction p = 0.93). MRA-induced hyperkalaemia was less frequent in patients with COPD.\ud \ud Conclusions:\ud \ud In RALES and EMPHASIS-HF, one-in-seven patients with HFrEF had coexisting COPD. HFrEF patients with COPD had worse outcomes than those without. The benefits of MRAs were consistent, regardless of COPD status.

Sudden death is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyse the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias.Adverse event reports related to ventricular arrhythmias were examined in PARADIGM-HF. The effect of randomized treatment on two arrhythmia outcomes was analysed: ventricular arrhythmias and the composite of a ventricular arrhythmia, implantable cardioverter defibrillator (ICD) shock or resuscitated cardiac arrest. The risk of death related to a ventricular arrhythmia was examined in time-updated models. The interaction between heart failure aetiology, or baseline ICD/cardiac resynchronization therapy-defibrillator (CRT-D) use, and the effect of sacubitril/valsartan was analysed. Of the 8399 participants, 333 (4.0%) reported a ventricular arrhythmia and 372 (4.4%) the composite arrhythmia outcome. Ventricular arrhythmias were associated with higher mortality. Compared with enalapril, sacubitril/valsartan reduced the risk of a ventricular arrhythmia (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95; p = 0.015) and the composite arrhythmia outcome (HR 0.79, 95% CI 0.65-0.97; p = 0.025). The treatment effect was maintained after adjustment and accounting for the competing risk of death. Baseline ICD/CRT-D use did not modify the effect of sacubitril/valsartan, but aetiology did: HR in patients with an ischaemic aetiology 0.93 (95% CI 0.71-1.21) versus 0.53 (95% CI 0.37-0.78) in those without an ischaemic aetiology (p for interaction = 0.020).Sacubitril/valsartan reduced the incidence of investigator-reported ventricular arrhythmias in patients with HFrEF. This effect may have been greater in patients with a non-ischaemic aetiology.

Background Loop diuretics are the mainstay of congestion treatment in patients with heart failure (HF). We assessed the association between baseline loop diuretic use and outcome. We also compared the increment in risk related to diuretic dose with conventional prognostic enrichment criteria used in the EMPHASIS-HF trial, which included patients with systolic HF and mild symptoms, such as prior hospitalization and elevated natriuretic peptides. Methods Individual analyses were performed according to baseline loop diuretic usage (furosemide-equivalent dose > 40 mg, 1-40 mg, and no furosemide), and according to enrichment criteria adopted in the trial [i.e. recent hospitalization (< 30 days or 30 to 180 days prior to randomization) due to HF or other cardiovascular cause, or elevated natriuretic peptides]. The primary endpoint was a composite of cardiovascular death or HF hospitalization. Results Loop diuretic usage at baseline (HR for > 40 mg furosemide-equivalent dose = 3.16, 95% CI 2.43-4.11; HR for 1-40 mg = 2.06, 95% CI 1.60-2.65) was significantly associated with a higher risk for the primary endpoint in a stepwise manner when compared to no baseline loop diuretic usage. In contrast, the differences in outcome rates were more modest when using history of hospitalization and/or BNP: all HR ranged from 1 (reference, non-HF related CV hospitalization > 30 days) to 2.04 (HF hospitalization < 30 days). The effect of eplerenone on the primary endpoint was consistent across subgroups in both analyses (P for interaction >= 0.2 for all). Conclusions Loop diuretic usage (especially at doses > 40 mg) identified patients at higher risk than history of HF hospitalization and/or high BNP blood concentrations. Graphic abstract

Background : N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma concentrations are independent prognostic markers in patients with heart failure and reduced ejection fraction (HFrEF). Whether a differential risk association between NT-proBNP plasma concentrations and risk of cardiovascular (CV) vs non-CV adverse events exists is not well known. Objective : To assess if there is a differential proportional risk of CV vs non-CV adverse events by NT-proBNP plasma concentrations. Methods : In this post hoc combined analysis of PARADIGM-HF and ATMOSPHERE trials, proportion of CV vs non-CV mortality and hospitalizations were assessed by NT-proBNP levels ( 3000 pg/mL) at baseline using Cox regression adjusting for traditional risk factors. Results : A total of 14,737 patients with mean age of 62 ± 8 years (24% history of atrial fibrillation [AF]) were studied. For CV deaths, the event rates per 1000 patient-years steeply increased from 33.8 in the ≤400 pg/mL group to 142.3 in the ≥3000 pg/mL group, while the non-CV death event rates modestly increased from 9.0 to 22.7, respectively. Proportion of non-CV deaths decreased across the 5 NT-proBNP groups (21.1%, 18.4%, 17.9%, 17.4%, and 13.7% respectively). Similar trend was observed for non-CV hospitalizations (46.4%, 42.6%, 42.9%, 42.0%, and 36.9% respectively). These results remained similar when stratified according to the presence of AF at baseline and prior HF hospitalization within last 12 months. Conclusions : The absolute CV event rates per patient years of follow-up were greater and had higher stepwise increases than non-CV event rates across a broad range of NT-proBNP plasma concentrations indicating a differential risk of CV events at varying baseline NT-proBNP values. These results have implications for future design of clinical trials.

Background Sudden death (SD) and pump failure death (PFD) are the two leading causes of death in patients with heart failure and reduced ejection fraction (HFrEF). Objective Identifying patients at higher risk for mode-specific death would allow better targeting of individual patients for relevant device and other therapies. Methods We developed models in 7156 patients with HFrEF from the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, using Fine-Gray regressions counting other deaths as competing risks. The derived models were externally validated in the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure (ATMOSPHERE) trial. Results NYHA class and NT-proBNP were independent predictors for both modes of death. The SD model additionally included male sex, Asian or Black race, prior CABG or PCI, cancer history, MI history, treatment with LCZ696 vs. enalapril, QRS duration and ECG left ventricular hypertrophy. While LVEF, ischemic etiology, systolic blood pressure, HF duration, ECG bundle branch block, and serum albumin, chloride and creatinine were included in the PFD model. Model discrimination was good for SD and excellent for PFD with Harrell’s C of 0.67 and 0.78 after correction for optimism, respectively. The observed and predicted incidences were similar in each quartile of risk scores at 3 years in each model. The performance of both models remained robust in ATMOSPHERE. Conclusion We developed and validated models which separately predict SD and PFD in patients with HFrEF. These models may help clinicians and patients consider therapies targeted at these modes of death. Trial registration number PARADIGM-HF: ClinicalTrials.gov NCT01035255, ATMOSPHERE: ClinicalTrials.gov NCT00853658. Graphics abstract

Aims Patients with heart failure with reduced ejection fraction (HFrEF) are at significant risk of stroke. Anticoagulation reduces this risk in patients with and without atrial fibrillation (AF), but the risk-to-benefit balance in the latter group, overall, is not favourable. Identification of patients with HFrEF, without AF, at the highest risk of stroke may allow targeted and safer use of prophylactic anticoagulant therapy. Methods and results In a pooled patient-level cohort of the PARADIGM-HF, ATMOSPHERE, and DAPA-HF trials, a previously derived simple risk model for stroke, consisting of three variables (history of prior stroke, insulin-treated diabetes, and plasma N-terminal pro-B-type natriuretic peptide level), was validated. Of the 20 159 patients included, 12 751 patients did not have AF at baseline. Among patients without AF, 346 (2.7%) experienced a stroke over a median follow up of 2.0 years (rate 11.7 per 1000 patient-years). The risk for stroke increased with increasing risk score: fourth quintile hazard ratio (HR) 2.35 [95% confidence interval (CI) 1.60–3.45]; fifth quintile HR 3.73 (95% CI 2.58–5.38), with the first quintile as reference. For patients in the top quintile, the rate of stroke was 21.2 per 1000 patient-years, similar to participants with AF not receiving anticoagulation (20.1 per 1000 patient-years). Model discrimination was good with a C-index of 0.84 (0.75–0.91). Conclusion It is possible to identify a subset of HFrEF patients without AF with a stroke-risk equivalent to that of patients with AF who are not anticoagulated. In these patients, the risk-to-benefit balance might justify the use of prophylactic anticoagulation, but this hypothesis needs to be tested prospectively.

BACKGROUND The incidence of pneumonia and subsequent outcomes has not been compared in patients with heart failure and reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF).OBJECTIVES This study aimed to examine the rate and impact of pneumonia in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) and PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in Heart Failure with Preserved Ejection Fraction) trials.METHODS The authors analyzed the incidence of investigator-reported pneumonia and the rates of HF hospitalization, cardiovascular death, and all-cause death before and after the occurrence of pneumonia, and estimated risk after the first occurrence of pneumonia in unadjusted and adjusted analyses (the latter including N-terminal pro-B-type natriuretic peptide).RESULTS In PARADIGM-HF, 528 patients (6.3%) developed pneumonia after randomization, giving an incidence rate of 29 (95% CI: 27 to 32) per 1,000 patient-years. In PARAGON-HF, 510 patients (10.6%) developed pneumonia, giving an incidence rate of 39 (95% CI: 36 to 42) per 1,000 patient-years. The subsequent risk of all trial outcomes was elevated after the occurrence of pneumonia. In PARADIGM-HF, the adjusted hazard ratio (HR) for the risk of death from any cause was 4.34 (95% CI: 3.73 to 5.05). The corresponding adjusted HR in PARAGON-HF was 3.76 (95% CI: 3.09 to 4.58).CONCLUSIONS The incidence of pneumonia was high in patients with HF, especially HFpEF, at around 3 times the expected rate. A first episode of pneumonia was associated with 4-fold higher mortality. (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF], NCT01035255; Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] With ARB [Angiotensin Receptor Blocker] Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF], NCT01920711) (J Am Coll Cardiol 2021;77:1961-73) (c) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background Sudden death (SD) and pump failure death (PFD) are leading modes of death in heart failure and preserved ejection fraction (HFpEF). Risk stratification for mode-specific death may aid in patient enrichment for new device trials in HFpEF. Methods Models were derived in 4116 patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-Preserve), using competing risks regression analysis. A series of models were built in a stepwise manner, and were validated in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved and Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trials. Results The clinical model for SD included older age, men, lower LVEF, higher heart rate, history of diabetes or myocardial infarction, and HF hospitalization within previous 6 months, all of which were associated with a higher SD risk. The clinical model predicting PFD included older age, men, lower LVEF or diastolic blood pressure, higher heart rate, and history of diabetes or atrial fibrillation, all for a higher PFD risk, and dyslipidaemia for a lower risk of PFD. In each model, the observed and predicted incidences were similar in each risk subgroup, suggesting good calibration. Model discrimination was good for SD and excellent for PFD with Harrell’s C of 0.71 (95% CI 0.68–0.75) and 0.78 (95% CI 0.75–0.82), respectively. Both models were robust in external validation. Adding ECG and biochemical parameters, model performance improved little in the derivation cohort but decreased in validation. Including NT-proBNP substantially increased discrimination of the SD model, and simplified the PFD model with marginal increase in discrimination. Conclusions The clinical models can predict risks for SD and PFD separately with good discrimination and calibration in HFpEF and are robust in external validation. Adding NT-proBNP further improved model performance. These models may help to identify high-risk individuals for device intervention in future trials. Clinical trial registration I-Preserve: ClinicalTrials.gov NCT00095238; TOPCAT: ClinicalTrials.gov NCT00094302; CHARM-Preserved: ClinicalTrials.gov NCT00634712. Graphic abstract

Objectives The purpose of this study was to investigate the effect of sacubitril/valsartan therapy on sudden cardiac death (SCD) according to the use of and eligibility for an implantable ...

Objectives The authors investigated the relationship between past or incident myocardial infarction (MI) and cardiovascular (CV) events in heart failure with preserved ejection fraction (HFpEF). Background MI and HFpEF share some common risk factors. The prognostic significance of MI in patients with HFpEF is uncertain. Methods The authors pooled data from 3 trials—CHARM Preserved (Candesartan Cilexietil in Heart Failure Assessment of Reduction in Mortality and Morbidity), I-Preserve (Irbesartan in Heart Failure With Preserved Systolic Function), and the Americas region of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) (N = 8,916)—and examined whether MI before or following enrollment independently predicted CV death and heart failure (HF) hospitalization. Results At baseline, 2,668 patients (30%) had history of MI. Prior MI was independently associated with greater risk of CV death (4.7 vs. 3.5 events/100 patient-years [py], adjusted hazard ratio [HR]: 1.42 [95% confidence interval (CI): 1.23 to 1.64]; p Conclusions Prior MI in HFpEF is associated with greater CV and sudden death but similar risk of HF outcomes. Patients with HFpEF who experience MI are at high risk of subsequent CV death and HF hospitalization. These data highlight the importance of primary and secondary prevention of MI in patients with HFpEF. (Candesartan Cilexietil in Heart Failure Assessment of Reduction in Mortality and Morbidity [CHARM Preserved]; NCT00634712; Irbesartan in Heart Failure With Preserved Systolic Function [I-Preserve]; NCT00095238; and Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302)

Aims: \ud Frailty, characterized by loss of homeostatic reserves and increased vulnerability to physiological decompensation, results from an aggregation of insults across multiple organ systems. Frailty can be quantified by counting the number of ‘health deficits’ across a range of domains. We assessed the frequency of, and outcomes related to, frailty in patients with heart failure and reduced ejection fraction (HFrEF).\ud \ud Methods and results: \ud Using a cumulative deficits approach, we constructed a 42‐item frailty index (FI) and applied it to identify frail patients enrolled in two HFrEF trials (PARADIGM‐HF and ATMOSPHERE). In keeping with previous studies, patients with FI ≤0.210 were classified as non‐frail and those with higher scores were divided into two categories using score increments of 0.100. Clinical outcomes were examined, adjusting for prognostic variables. Among 13 625 participants, mean (± standard deviation) FI was 0.250 (0.10) and 8383 patients (63%) were frail (FI >0.210). The frailest patients were older and had more symptoms and signs of heart failure. Women were frailer than men. All outcomes were worse in the frailest, with high rates of all‐cause death or all‐cause hospitalization: 40.7 (39.1–42.4) vs. 22.1 (21.2–23.0) per 100 person‐years in the non‐frail; adjusted hazard ratio 1.63 (1.53–1.75) (P

Background: While disease-modifying therapies exist for heart failure (HF) with reduced left ventricular ejection fraction (LVEF), few options are available for patients in the higher range of LVEF (>40%). Sacubitril/valsartan has been compared with a renin-angiotensin-aldosterone–system inhibitor alone in 2 similarly designed clinical trials of patients with reduced and preserved LVEF, permitting examination of its effects across the full spectrum of LVEF. Methods: We combined data from PARADIGM-HF (LVEF eligibility≤40%; n=8399) and PARAGON-HF (LVEF eligibility≥45%; n=4796) in a prespecified pooled analysis. We divided randomized patients into LVEF categories: ≤22.5% (n=1269), >22.5% to 32.5% (n=3987), >32.5% to 42.5% (n=3143), > 42.5% to 52.5% (n=1427), > 52.5% to 62.5% (n=2166), and >62.5% (n=1202). We assessed time to first cardiovascular death and HF hospitalization, its components, and total heart failure hospitlizations, all-cause mortality, and noncardiovascular mortality. Incidence rates and treatment effects were examined across categories of LVEF. Results: Among 13 195 randomized patients, we observed lower rates of cardiovascular death and HF hospitalization, but similar rates of noncardiovascular death, among patients in the highest versus the lowest groups. Overall sacubitril/valsartan was superior to renin-angiotensin-aldosterone–system inhibition for first cardiovascular death or heart failure hospitalization (Hazard Ratio [HR] 0.84 [95% CI, 0.78–0.90]), cardiovascular death (HR 0.84 [95% CI, 0.76–0.92]), heart failure hospitalization (HR 0.84 [95% CI, 0.77–0.91]), and all-cause mortality (HR 0.88 [95% CI, 0.81–0.96]). The effect of sacubitril/valsartan was modified by LVEF (treatment-by-continuous LVEF interaction P =0.02), and benefit appeared to be present for individuals with EF primarily below the normal range, although the treatment benefit for cardiovascular death diminished at a lower ejection fraction. We observed effect modification by LVEF on the efficacy of sacubitril/valsartan in both men and women with respect to composite total HF hospitalizations and cardiovascular death, although women derived benefit to higher ejection fractions. Conclusions: The therapeutic effects of sacubitril/valsartan, compared with a renin-angiotensin-aldosterone–system inhibitor alone, vary by LVEF with treatment benefits, particularly for heart failure hospitalization, that appear to extend to patients with heart failure and mildly reduced ejection fraction. These therapeutic benefits appeared to extend to a higher LVEF range in women compared with men. Clinical Trial Registration: https://www.clinicaltrials.gov . Unique identifiers: NCT01920711 (PARAGON-HF), NCT01035255 (PARADIGM-HF).

In healthcare systems patient engagement and care satisfaction are less than optimal. Different solutions have been proposed to recognise the patient in health care, including person-centred care. The University of Gothenburg Centre for Person-Centred Care (GPCC) steering committee formulated three ‘simple routines’ to initiate, integrate and safeguard person-centred care in daily clinical practice. These routines are: the patient narrative followed by an agreed health plan which is then safeguarded by documentation. Health care professionals need to know how health processes are strengthened in a relationship where patients are accepted as persons with their own will and emotions and in which individual responsibilities and capabilities are highlighted. A person-centred perspective uses ethics as a springboard. Such an ethical view can briefly be formulated by: “To aim for the good life, with and for others in just institutions”. When the starting point is ethics and each person is understood as a unique individual, care actions will never be the same for each patient. By asking for the patients’ understanding of the condition and treatment relative to their lives in general, professionals can understand what health, illness, treatment and care convey to patients and their relatives. The patient narratives are obviously very important in formulating the health plan. Controlled studies have found several benefits from implementing person-centred practices, including improved quality of life, maintained self-efficacy and reduced health costs.

ImportanceHeart failure (HF) treatment recommendations are centered on New York Heart Association (NYHA) classification, such that most apparently asymptomatic patients are not eligible for disease-modifying therapies.ObjectivesTo assess within-patient variation in NYHA classification over time, the association between NYHA class and an objective measure of HF severity (N-terminal pro–B-type natriuretic peptide [NT-proBNP] level), and their association with long-term prognosis in the PARADIGM-HF trial.Design, Setting, and ParticipantsAll patients in PARADIGM-HF were in NYHA class II or higher at baseline and were treated with sacubitril-valsartan during a 6- to 10-week run-in period before randomization. Patients classified as NYHA class I, II, and III in PARADIGM-HF were compared at randomization.ExposuresNYHA class at randomization after 6 to 10 weeks of the run-in period.Main Outcomes and MeasuresPrimary outcome was cardiovascular death or first HF hospitalization. Logistic regression models, areas under the receiver operating characteristic curve (AUC), kernel density estimation overlaps, and Cox proportional hazards models were used.ResultsThe analysis included 8326 patients with known NYHA classification at randomization. Of 389 patients in NYHA class I, 228 (58%) changed functional class during the first year after randomization. Level of NT-proBNP was a poor discriminator of NYHA classification: for NYHA class I vs II, the AUC was 0.51 (95% CI, 0.48-0.54). For NT-proBNP level, estimated kernel density overlap was 93% between NYHA class I vs II, 79% between NYHA I vs III, and 83% between NYHA II vs III. Patients classified as NYHA III displayed a distinctively higher rate of cardiovascular events (NYHA III vs I, hazard ratio [HR], 1.84; 95% CI, 1.44-2.37; NYHA III vs II, HR, 1.49; 95% CI, 1.35-1.64). Patients in NYHA class I and II revealed lower event rates (NYHA II vs I, HR, 1.24; 95% CI, 0.97-1.58). Stratification by NT-proBNP level (Conclusions and RelevanceIn this study, patients in NYHA class I and II overlapped substantially in objective measures and long-term prognosis. Physician-defined “asymptomatic” functional class concealed patients who were at substantial risk for adverse outcomes. NYHA classification might be limited to differentiate mild forms of HF.Trial RegistrationClinicalTrials.gov Identifier: NCT01035255

Aims: Patients with heart failure are at higher risk of progression to end-stage renal disease (ESRD), regardless of ejection fraction (EF). We assessed the renal effects of angiotensin–neprilysin inhibition in a pooled analysis of 13 195 patients with heart failure with reduced and preserved EF. Methods and results: We combined data from PARADIGM-HF (EF ≤40%; n = 8399) and PARAGON-HF (EF ≥45%; n = 4796) in a pre-specified pooled analysis. We assessed the effect of treatment (sacubitril/valsartan vs. enalapril or valsartan) on a composite of either ≥50% reduction in estimated glomerular filtration rate (eGFR), ESRD, or death from renal causes, in addition to changes in eGFR slope. We assessed whether baseline renal function or EF modified the effect of therapy on renal outcomes. At randomization, eGFR was 68 ± 20 ml/min/1.73 m2 in PARADIGM-HF and 63 ± 19 ml/min/1.73 m2 in PARAGON-HF. The composite renal outcome occurred in 70 of 6594 patients (1.1%) in the sacubitril/valsartan group and in 123 of 6601 patients (1.9%) in the valsartan or enalapril group (hazard ratio 0.56, 95% confidence interval [CI] 0.42–0.75; p < 0.001). The mean eGFR change was −1.8 (95% CI −1.9 to −1.7) ml/min/1.73 m2/year for the sacubitril/valsartan group, compared with −2.4 (95% CI −2.5 to −2.2) ml/min/1.73 m2/year for the valsartan or enalapril group. The treatment effect on the composite renal endpoint was not modified by categories of baseline eGFR (p-interaction = 0.64), but was most pronounced in those with baseline EF between 30% and 60% (p-interaction = 0.001). Conclusions: In patients with heart failure, sacubitril/valsartan reduced the risk of serious adverse renal outcomes and slowed decline in eGFR, compared with valsartan or enalapril, independent of baseline renal function.

BACKGROUND Visit-to-visit office blood pressure (BP) variability (BPV) has been associated with morbidity and mortality outcomes in several cardiovascular conditions. The aim of this study was to evaluate the association between BPV and outcomes in patients with heart failure and reduced ejection fraction and the effect of eplerenone on BPV. METHODS AND RESULTS We evaluated the associations between BPV, calculated as SBP coefficient of variation (SBP-CoV = SD/mean × 100%), and the primary composite endpoint of cardiovascular mortality or heart failure hospitalization (HFH), and its components, in 2549 patients from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial. Lower SBP-CoV was independently associated with a higher risk of all the studied outcomes, while higher as well as lower SBP-CoV were associated with a higher risk of cardiovascular death. After a median follow-up period of 21 months the risk of the composite outcome of cardiovascular death or HFH was almost double in the lower SBP-CoV tertile as compared with the intermediate tertile [adjusted hazard ratio: 2.01, 95% confidence interval (1.62-2.51), P

BACKGROUND Sick leave due to common mental disorders (CMDs) is a public health problem in several countries, including Sweden. Given that symptom relief does not necessarily correspond to return to work, health care interventions focusing on factors that have proven important to influence the return to work process, such as self-efficacy, are warranted. Self-efficacy is also a central concept in person-centered care. OBJECTIVE The aim of this study is to evaluate the effects of a person-centered eHealth intervention for patients on sick leave due to CMDs. METHODS A randomized controlled trial of 209 patients allocated to either a control group (107/209, 51.2%) or an intervention group (102/209, 48.8%) was conducted. The control group received usual care, whereas the intervention group received usual care with the addition of a person-centered eHealth intervention. The intervention was built on person-centered care principles and consisted of telephone support and a web-based platform. The primary outcome was a composite score of changes in general self-efficacy (GSE) and level of sick leave at the 6-month follow-up. An intention-to-treat analysis included all participants, and a per-protocol analysis consisted of those using both the telephone support and the web-based platform. RESULTS At the 3-month follow-up, in the intention-to-treat analysis, more patients in the intervention group improved on the composite score than those in the control group (20/102, 19.6%, vs 10/107, 9.3%; odds ratio [OR] 2.37, 95% CI 1.05-5.34; P=.04). At the 6-month follow-up, the difference was no longer significant between the groups (31/100, 31%, vs 25/107, 23.4%; OR 1.47, 95% CI 0.80-2.73; P=.22). In the per-protocol analysis, a significant difference was observed between the intervention and control groups at the 3-month follow-up (18/85, 21.2%, vs 10/107, 9.3%; OR 2.6, 95% CI 1.13-6.00; P=.02) but not at 6 months (30/84, 35.7%, vs 25/107, 23.4%; OR 1.8, 95% CI 0.97-3.43; P=.06). Changes in GSE drove the effects in the composite score, but the intervention did not affect the level of sick leave. CONCLUSIONS A person-centered eHealth intervention for patients on sick leave due to CMDs improved GSE but did not affect the level of sick leave. CLINICALTRIAL ClinicalTrials.gov NCT03404583; https://clinicaltrials.gov/ct2/show/NCT03404583

Background Sick leave due to common mental disorders (CMDs) is a public health problem in several countries, including Sweden. Given that symptom relief does not necessarily correspond to return to work, health care interventions focusing on factors that have proven important to influence the return to work process, such as self-efficacy, are warranted. Self-efficacy is also a central concept in person-centered care. Objective The aim of this study is to evaluate the effects of a person-centered eHealth intervention for patients on sick leave due to CMDs. Methods A randomized controlled trial of 209 patients allocated to either a control group (107/209, 51.2%) or an intervention group (102/209, 48.8%) was conducted. The control group received usual care, whereas the intervention group received usual care with the addition of a person-centered eHealth intervention. The intervention was built on person-centered care principles and consisted of telephone support and a web-based platform. The primary outcome was a composite score of changes in general self-efficacy (GSE) and level of sick leave at the 6-month follow-up. An intention-to-treat analysis included all participants, and a per-protocol analysis consisted of those using both the telephone support and the web-based platform. Results At the 3-month follow-up, in the intention-to-treat analysis, more patients in the intervention group improved on the composite score than those in the control group (20/102, 19.6%, vs 10/107, 9.3%; odds ratio [OR] 2.37, 95% CI 1.05-5.34; P=.04). At the 6-month follow-up, the difference was no longer significant between the groups (31/100, 31%, vs 25/107, 23.4%; OR 1.47, 95% CI 0.80-2.73; P=.22). In the per-protocol analysis, a significant difference was observed between the intervention and control groups at the 3-month follow-up (18/85, 21.2%, vs 10/107, 9.3%; OR 2.6, 95% CI 1.13-6.00; P=.02) but not at 6 months (30/84, 35.7%, vs 25/107, 23.4%; OR 1.8, 95% CI 0.97-3.43; P=.06). Changes in GSE drove the effects in the composite score, but the intervention did not affect the level of sick leave. Conclusions A person-centered eHealth intervention for patients on sick leave due to CMDs improved GSE but did not affect the level of sick leave. Trial Registration ClinicalTrials.gov NCT03404583; https://clinicaltrials.gov/ct2/show/NCT03404583