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Background Heart failure (HF) is a life-threatening condition and optimal handling is necessary to reduce risk of therapy failure. The impact of the duration of HF diagnosis on HF outcome has not previously been examined. The objectives of this study were (I) to evaluate the impact of patient age on clinical outcomes, (II) to evaluate the impact of duration of the HF disease on outcomes, and (III) to evaluate the impact of age and HF duration on B-type Natriuretic Peptide (BNP) concentration in a population of HF patients. Methods and results In the UPSTEP (Use of PeptideS in Tailoring hEart failure Project) study we retrospectively evaluated how age and HF duration affected HF outcome. HF duration was divided into < 1 year, 1–5 years and > 5 years. A multivariate Cox proportional hazard regression analysis showed that HF duration influenced outcome more than age, even when adjusted for comorbidities(< 1 year versus > 5 years: HR 1.65; 95% CI 1.28–2.14; P < 0.0002) on HF mortality and hospitalisations. The influence of age on BNP showed increased BNP as age increased. However, there was a significant effect on BNP concentration when comparing HF duration of less than one year to HF duration to more than five years, even when adjusted for age. Conclusions Patients with longer HF duration had significantly worse outcome compared to those with short HF duration, even when adjusted for patient age and comorbidities. Age did not influence outcome but had an impact on BNP concentration; however, BNP concentration increased as HF duration increased. [ABSTRACT FROM AUTHOR]

Objectives: B-type natriuretic peptide (BNP) levels predict prognosis and outcome in heart failure (HF) patients. To evaluate the optimal cut-off level of BNP to predict death, need for hospitalization, and worsening HF, and also to determine the optimal time to apply the chosen cut-off value.Design: In a sub-study from the Use of PeptideS in Tailoring hEart failure Project or UPSTEP study where tailoring treatment of HF by BNP level was evaluated, we assessed the change in percentage between levels of BNP at study start versus a specific week (2, 6, 10, 16, 24, 36, or 48) during the follow-up period.Results: The optimum cut-off percentage levels were obtained using a Cox proportional regression analysis of death, hospitalization, and worsening HF. A decrease in BNP by less than 40% in week 16 compared with study start and/or a BNP > 300 ng/L presented the highest hazard ratio (HR) for a non-responder to reach a combined endpoint (HR: 2.43; 95% confidence interval or CI: 1.61-3.65; p < 0.00003). This definition gave a 78% risk reduction of cardiovascular (CV) mortality (p > 0.0005) and an 89% risk reduction of HF mortality (p > 0.004), and reduced risk of CV and HF hospitalization for the responders.Conclusions: Patients with a decrease in BNP of more than 40% compared with that at study start and/or a BNP level below 300 ng/L at week 16 had a significantly reduced risk of CV and HF mortality and hospitalization. [ABSTRACT FROM AUTHOR]

The adenosine-requiring physiological index fractional flow reserve (FFR) is the gold-standard method for determining the significance of intermediate lesions, while the resting full-cycle ratio (RFR) is a novel nonhyperaemic index without the need for adenosine administration. The aim of this study was to investigate the degree of concordance between RFR and FFR in indicating the need for revascularisation in patients with intermediate coronary lesions. This was a retrospective, registry-based study utilising data from the SWEDEHEART registry. Patients treated at Ryhov County Hospital in Jönköping, Sweden, between the 1st of January 2020 and the 30th of September 2021, were included. The degree of correlation and concordance between RFR and FFR was determined, both when used with a single cut-off (significant stenosis if RFR ≤0.89) and with a hybrid approach (significant stenosis if RFR ≤0.85, not significant if RFR ≥0.94, and FFR measurement when RFR was in the grey zone 0.86–0.93). The study population consisted of 143 patients with 200 lesions. The overall correlation between FFR and RFR was significant (r = 0.715, R2 = 0.511, p ≤ 0.01). A strong correlation was seen for lesions in the left anterior descending artery (LAD) and the left circumflex artery (LCX) (r = 0.748 and 0.742, respectively, both p ≤ 0.01), while the correlation in the right coronary artery (RCA) was moderate (r = 0.524, p ≤ 0.01). The overall concordance between FFR and RFR using a single cut-off was 79.0%. With a hybrid cut-off approach, the degree of concordance was 91%, with no need of adenosine in 50.5% of the lesions. In conclusion, there was a strong correlation and a high degree of concordance between FFR and RFR in determining the significance of a stenosis. The use of a hybrid approach could improve the identification of physiologically significant stenoses while minimising the use of adenosine. [ABSTRACT FROM AUTHOR]

Aim To determine whether brain natriuretic peptide (BNP)-guided heart failure (HF) treatment improves morbidity and/or mortality when compared with conventional treatment. Methods and results UPSTEP was an investigator-initiated, randomized, parallel group, multicentre study with a PROBE design. Symptomatic patients with worsening HF, New York Heart Association class II–IV, ejection fraction <40% and elevated BNP levels, were included. All patients (n= 279) were treated according to recommended guidelines and randomized to BNP-guided (BNP) or to conventional (CTR) HF treatment. The goal was to reduce BNP levels to <150 ng/L in younger patients and <300 ng/L in elderly patients, respectively. The primary outcome was a composite of death due to any cause, need for hospitalization and worsening HF. The study groups were well matched, including for BNP concentration at entry (mean: 808 vs. 899 ng/L; P= 0.34). There were no significant differences between the groups regarding either the primary outcome (P = 0.18) or any of the secondary endpoints. There were no differences for the pre-specified analyses; days out of hospital, and younger vs. elderly. A subgroup analysis comparing treatment responders (>30% decrease in baseline BNP value) vs. non-responders found improved survival among responders (P< 0.0001 for the primary outcome), and all of the secondary endpoints were also improved. Conclusions Morbidity and mortality were not improved by HF treatment guided by BNP levels. However, BNP responders had a significantly better clinical outcome than non-responders. Future research is needed to elucidate the responsible pathophysiological mechanisms in this sub-population. [ABSTRACT FROM AUTHOR]

Aims: To investigate incidence, predictors and prognostic implications of longitudinal New York Heart Association (NYHA) class changes (i.e. improving or worsening vs. stable NYHA class) in heart failure (HF) across the ejection fraction (EF) spectrum. Methods and results: From the Swedish HF Registry, 13 535 patients with EF and ≥2 NYHA class assessments were considered. Multivariable multinomial regressions were fitted to identify the independent predictors of NYHA change. Over a 1‐year follow‐up, 69% of patients had stable, 17% improved, and 14% worsened NYHA class. Follow‐up in specialty care predicted improving NYHA class, whereas an in‐hospital patient registration, lower EF, renal disease, lower mean arterial pressure, older age, and longer HF duration predicted worsening. The association between NYHA change and subsequent outcomes was assessed with multivariable Cox models. When adjusting for the NYHA class at baseline, improving NYHA class was independently associated with lower while worsening with higher risk of all‐cause and cardiovascular mortality, and first HF hospitalization. After adjustment for the NYHA class at follow‐up, NYHA class change did not predict morbidity/mortality. NYHA class assessment at baseline and follow‐up predicted morbidity/mortality on top of the changes. Results were consistent across the EF spectrum. Conclusion: In a large real‐world HF population, NYHA class trajectories predicted morbidity/mortality after extensive adjustments. However, the prognostic role was entirely explained by the resulting NYHA class, i.e. the follow‐up value. Our results highlight that considering one‐time NYHA class assessment, rather than trajectories, might be the preferable approach in clinical practice and for clinical trial design. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the effects of a brief dyadic cognitive behavioural therapy (CBT) programme on the health-related quality of life (HRQoL), as well as the sense of coherence in atrial fibrillation patients, up to 12 months post atrial fibrillation. Methods: A longitudinal randomised controlled trial with a pre and 12-month post-test recruitment of 163 persons and their spouses, at a county hospital in southern Sweden. In all, 104 persons were randomly assigned to either a CBT (n=56) or a treatment as usual (TAU) group (n=55). The primary outcome was changes in the HRQoL (Euroqol questionnaire; EQ-5D), and the secondary outcomes were changes in psychological distress (hospital anxiety and depression scale; HADS) and sense of coherence (sense of coherence scale; SOC-13). Results: At the 12-month follow-up, the CBT group experienced a higher HRQoL than the TAU group (mean changes in the CBT group 0.062 vs. mean changes in the TAU group −0.015; P=0.02). The sense of coherence improved in the CBT group after the 12-month follow-up, compared to the TAU group (mean changes in the CBT group 0.062 vs. mean changes in the TAU group −0.16; P=0.04). The association between the intervention effect and the HRQoL was totally mediated by the sense of coherence (z=2.07, P=0.04). Conclusions: A dyadic mindfulness-based CBT programme improved HRQoL and reduced psychological distress up to 12 months post atrial fibrillation. The sense of coherence strongly mediated the HRQoL; consequently, the sense of coherence is an important determinant to consider when designing programmes for atrial fibrillation patients. [ABSTRACT FROM AUTHOR]

Aims: Previous analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear.Methods and Results: To determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) ≤45%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62-0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67-0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76-1.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67-1.53, P = 0.97; interactions P < 0.02). Age (74 ± 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P < 0.01; increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P < 0.01; (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02).Conclusion: The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients. [ABSTRACT FROM AUTHOR]

Aims Previous analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear. Methods and results To determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) ≤45%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62 - 0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67 - 0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76 - 1.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67 - 1.53, P = 0.97; interactions P < 0.02). Age (74 ' 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P < 0.01; increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P < 0.01; (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02). Conclusion The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients. [ABSTRACT FROM AUTHOR]

Background: We estimated the effectiveness of serial B-type natriuretic peptide (BNP) blood testing to guide up-titration of medication compared with symptom-guided up-titration of medication in patients with heart failure (HF). Methods: Systematic review and meta-analysis of randomised controlled trials (RCTs). We searched: MEDLINE (Ovid) 1950 to 9/06/2016; Embase (Ovid), 1980 to 2016 week 23; the Cochrane Library; ISI Web of Science (Citations Index and Conference Proceedings). The primary outcome was all-cause mortality; secondary outcomes were death related to HF, cardiovascular death, all-cause hospital admission, hospital admission for HF, adverse events, and quality of life. IPD were sought from all RCTs identified. Random-effects meta-analyses (two-stage) were used to estimate hazard ratios (HR) and confidence intervals (CIs) across RCTs, including HR estimates from published reports of studies that did not provide IPD. We estimated treatment-by-covariate interactions for age, gender, New York Heart Association (NYHA) class, HF type; diabetes status and baseline BNP subgroups. Dichotomous outcomes were analysed using random-effects odds ratio (OR) with 95% CI. Results: We identified 14 eligible RCTs, five providing IPD. BNP-guided therapy reduced the hazard of hospital admission for HF by 19% (13 RCTs, HR 0.81, 95% CI 0.68 to 0.98) but not all-cause mortality (13 RCTs; HR 0.87, 95% CI 0.75 to 1.01) or cardiovascular mortality (5 RCTs; OR 0.88, 95% CI 0.67 to 1.16). For all-cause mortality, there was a significant interaction between treatment strategy and age ( p = 0.034, 11 RCTs; HR 0.70, 95% CI 0.53–0.92, patients < 75 years old and HR 1.07, 95% CI 0.84–1.37, patients ≥ 75 years old); ejection fraction ( p = 0.026, 11 RCTs; HR 0.84, 95% CI 0.71–0.99, patients with heart failure with reduced ejection fraction (HFrEF); and HR 1.33, 95% CI 0.83–2.11, patients with heart failure with preserved ejection fraction (HFpEF)). Adverse events were significantly more frequent with BNP-guided therapy vs. symptom-guided therapy (5 RCTs; OR 1.29, 95% CI 1.04 to 1.60). Conclusion: BNP-guided therapy did not reduce mortality but reduced HF hospitalisation. The overall quality of the evidence varied from low to very low. The relevance of these findings to unselected patients, particularly those managed by community generalists, are unclear. Systematic review registration: PROSPERO CRD42013005335 [ABSTRACT FROM AUTHOR]