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Abstract Aims The detailed sub‐categories of death and hospitalization, and the impact of comorbidities on cause‐specific outcomes, remain poorly understood in heart failure (HF) with preserved ejection fraction (HFpEF). We sought to evaluate rates and predictors of cardiovascular (CV) and non‐CV outcomes in HFpEF. Methods The Karolinska–Rennes study was a bi‐national prospective observational study designed to characterize HFpEF (ejection fraction ≥45%). Patients were followed for cause‐specific death and hospitalization. Baseline characteristics were pre‐selected based on clinical relevance and potential eligibility criteria for HFpEF trials. The associations between characteristics and cause‐specific outcomes were assessed with univariable and multivariable Cox regressions. Results Five hundred thirty‐nine patients [56% females; median (inter‐quartile range) age 79 (72–84) years; NT‐proBNP/BNP 2448 (1290–4790)/429 (229–805) ng/L] were included. Over 1196 patient‐years follow‐up [median (min, max) 744 days (13–1959)], there were 159 (29%) deaths (13 per 100 patient‐years: CV 5.1 per 100, dominated by HF 3.9 per 100; and non‐CV 5.8 per 100, dominated by cancer, 2.3 per 100). There were 723 hospitalizations in 338 patients (63%; 60 per 100 patient‐years: CV 33 per 100, dominated by HF 17 per 100; and non‐CV 27 per 100, dominated by lung disease 5 per 100). Higher age and natriuretic peptides, lower serum natraemia and NYHA class III–IV were independent predictors of CV death; lower serum natraemia, anaemia and stroke of non‐CV death; and anaemia and lower serum natraemia of non‐CV death or hospitalizations. There were no apparent predictors of CV death or hospitalization. Conclusions In a clinical cohort hospitalized and diagnosed with HFpEF, death and hospitalization rates were roughly similar for CV and non‐CV causes. CV deaths were predicted primarily by severity of HF; non‐CV deaths primarily by anaemia and prior stroke. Lower serum sodium predicted both. Hospitalizations were difficult to predict.

In the recent years, there has been a burgeoning interest in Takotsubo syndrome (TTS), which is renowned as a specific form of reversible myocardial dysfunction. Despite the extensive literature available on TTS, clinicians still face several practical challenges associated with the diagnosis and management of this phenomenon. This potentially results in the underdiagnosis and improper management of TTS in clinical practice. The present paper, the first part (part-1) of the consensus report, aims to cover diagnostic and therapeutic challenges associated with TTS along with certain recommendations to combat these challenges.

Takotsubo syndrome (TTS) still remains as an enigmatic phenomenon. In particular, long-term challenges (including clinical recurrence and persistent symptoms) and specific entities in the setting of TTS have been the evolving areas of interest. On the other hand, a significant gap still exists regarding the proper risk-stratification of this phenomenon in the short and long terms. The present paper, the second part (part-2) of the consensus report, aims to discuss less well-known aspects of TTS including specific entities, challenges after recovery and risk-stratification.

Abstract Aims The prevalence of iron deficiency (ID) in newly diagnosed heart failure (HF) and the progression of ID in patients after initiation of HF therapy are unknown. We aimed to describe the natural trajectory of ID in patients with new onset HF during the first year after HF diagnosis, assessing associations between ID, clinical factors, and quality of life (QoL). Methods and results A prospective cohort of patients with new onset HF in hospitals or outpatient clinics at five major hospitals in Stockholm, Sweden, during 2015–2018 were analysed with clinical assessment, electrocardiogram, blood samples including iron levels, Minnesota living with heart failure questionnaire (MLHFQ), and echocardiogram at baseline and after 12 months. Of 547 patients with new‐onset HF, 482 (88%) had complete iron data at baseline. Median age was 70 years (interquartile range 61–77) and 311 (65%) were men; 55% of patients had ejection fraction (EF) ≤ 40%, 19% had EF 41–49%, and 26% had HF with preserved EF (HFpEF) [Correction added on 26 June 2024, after first online publication: The ‘Mean age was 70 years’ has been corrected to ‘Median age was 70 years’ in this version.]. At baseline, 163 patients (34%) had ID defined as ferritin

Abstract Background Epicardial adipose tissue (EAT) surrounds the heart and is hypothesised to play a role in the development of heart failure (HF). In this study, we first investigated the differences in gene expression between epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) in patients undergoing elective coronary artery bypass graft (CABG) surgery (n = 21; 95% male). Secondly, we examined the association between EAT and SAT in patients at risk for HF stage A (n = 12) and in pre-HF patients, who show signs but not symptoms of HF, stage B (n = 9). Results The study confirmed a distinct separation between EAT and SAT. In EAT 17 clusters of genes were present, of which several novel gene modules are associated with characteristics of HF. Notably, seven gene modules showed significant correlation to measures of HF, such as end diastolic left ventricular posterior wall thickness, e’mean, deceleration time and BMI. One module was particularly distinct in EAT when compared to SAT, featuring key genes such as FLT4, SEMA3A, and PTX3, which are implicated in angiogenesis, inflammation regulation, and tissue repair, suggesting a unique role in EAT linked to left ventricular dysfunction. Genetic expression was compared in EAT across all pre-HF and normal phenotypes, revealing small genetic changes in the form of 18 differentially expressed genes in ACC/AHA Stage A vs. Stage B. Conclusions The roles of subcutaneous and epicardial fat are clearly different. We highlight the gene expression difference in search of potential modifiers of HF progress. The true implications of our findings should be corroborated in other studies since HF ACC/AHA stage B patients are common and carry a considerable risk for progression to symptomatic HF.

Background Data on the benefits of cardiac resynchronization therapy (CRT) in patients with severe heart failure symptoms are limited. We investigated the relative effects of CRT in patients with ambulatory New York Heart Association (NYHA) IV versus III functional class at the time of device implantation. Methods and Results In this meta‐analysis, we pooled patient‐level data from the MIRACLE (Multicenter InSync Randomized Clinical Evaluation), MIRACLE‐ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation), and COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trials. Outcomes evaluated were time to the composite end point of the first heart failure hospitalization or all‐cause mortality, and time to all‐cause mortality alone. The association between CRT and outcomes was evaluated using a Bayesian hierarchical Weibull survival regression model. We assessed if this association differed between NYHA III and IV groups by adding an interaction term between CRT and NYHA class as a random effect. A sensitivity analysis was performed by including data from RAFT (Resynchronization‐Defibrillation for Ambulatory Heart Failure). Our pooled analysis included 2309 patients. Overall, CRT was associated with a longer time to heart failure hospitalization or all‐cause mortality (adjusted hazard ratio [aHR], 0.79 [95% credible interval [CI], 0.64–0.99]; posterior probability or P=0.044), with a similar association with time to all‐cause mortality (aHR, 0.78 [95% CI, 0.59–1.03]; P=0.083). Associations of CRT with outcomes were not significantly different for those in NYHA III and IV classes (ratio of aHR, 0.72 [95% CI, 0.30–1.27]; P=0.23 for heart failure hospitalization/mortality; ratio of aHR, 0.70 [95% CI, 0.35–1.34]; P=0.27 for all‐cause mortality alone). The sensitivity analysis, including RAFT data, did not show a significant relative CRT benefit between NYHA III and IV classes. Conclusions Overall, there was no significant difference in the association of CRT with either outcome for patients in NYHA functional class III compared with functional class IV.

Abstract New or mild heart failure (HF) is mainly caused by left ventricular dysfunction. We hypothesised that gene expression differ between the left (LV) and right ventricle (RV) and secondly by type of LV dysfunction. We compared gene expression through myocardial biopsies from LV and RV of patients undergoing elective coronary bypass surgery (CABG). Patients were categorised based on LV ejection fraction (EF), diastolic function and NT-proBNP into pEF (preserved; LVEF ≥ 45%), rEF (reduced; LVEF

Abstract Aims Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with cardiovascular (CV) and non‐CV events, but long‐term risk is poorly studied. We assessed incidence and predictors of the long‐term CV and non‐CV events. Methods and results Patients presenting with acute HF, EF ≥ 45%, and N‐terminal pro‐brain natriuretic peptide > 300 ng/L were enrolled in the Karolinska‐Rennes study in 2007–11 and were reassessed after 4–8 weeks in a stable state. Long‐term follow‐up was conducted in 2018. The Fine–Gray sub‐distribution hazard regression was used to detect predictors of CV and non‐CV deaths, investigated separately from baseline acute presentation (demographic data only) and from the 4–8 week outpatient visit (including echocardiographic data). Of 539 patients enrolled [median age 78 (interquartile range: 72–84) years; 52% female], 397 patients were available for the long‐term follow‐up. Over a median follow‐up time from acute presentation of 5.4 (2.1–7.9) years, 269 (68%) patients died, 128 (47%) from CV and 120 (45%) from non‐CV causes. Incidence rates per 1000 patient‐years were 62 [95% confidence interval (CI) 52–74] for CV and 58 (95% CI 48–69) for non‐CV death. Higher age and coronary artery disease (CAD) were independent predictors of CV death, and anaemia, stroke, kidney disease, and lower body mass index (BMI) and sodium concentrations of non‐CV death. From the stable 4–8 week visit, anaemia, CAD, and tricuspid regurgitation (>3.1 m/s) were independent predictors of CV death, and higher age of non‐CV death. Conclusions In patients with acute decompensated HFpEF, over 5 years of follow‐up, nearly two‐thirds of patients died, half from CV and the other half from non‐CV causes. CAD and tricuspid regurgitation were associated with CV death. Stroke, kidney disease, lower BMI, and lower sodium were associated with non‐CV death. Anaemia and higher age were associated with both outcomes. [Correction added on 24 March 2023, after first online publication: In the first sentence of the Conclusions, ‘two‐thirds’ has been inserted before ‘of patients died...’ in this version.]

Abstract Aim We present the baseline characteristics of the PREFERS Stockholm epidemiological study on the natural history and course of new onset heart failure (HF) aiming to improve phenotyping focusing on HF with preserved left ventricular ejection fraction (HFpEF) pathophysiology. Methods and results New onset HF patients diagnosed in hospital or at outpatient HF clinics were included at five Stockholm hospitals 2015–2018 and characterized by N‐terminal pro brain natriuretic peptide (NT‐proBNP), biomarkers, echocardiography, and cardiac magnetic resonance imaging (subset). HFpEF [left ventricular ejection fraction (LVEF) ≥ 50%] was compared with HF with mildly reduced LVEF (HFmrEF; LVEF 41–49%) and with HF with reduced LVEF (HFrEF; LVEF ≤ 40%). We included 547 patients whereof HFpEF (n = 137; 25%), HFmrEF (n = 61; 11%), and HFrEF (n = 349; 64%). HFpEF patients were older (76; 70–81 years; median; interquartile range) than HFrEF (67; 58–74; P 34 mL/m2 in 57% vs. 61% (P = 0.040). HFmrEF patients were intermediary between HFpEF and HFrEF for LV mass, LV volumes, and RV volumes but had the highest proportion of left ventricular hypertrophy and the lowest proportion of elevated E/é. Conclusions Phenotype data in new onset HF patients recruited in a broad clinical setting showed that 25% had HFpEF, were older, more often women, and had greater comorbidity burden. PREFERS is well suited to further explore biomarker and imaging components of HFpEF pathophysiology and may contribute to the emerging knowledge of HF epidemiology. Clinical trial registration: Clinicaltrials.gov identifier: NCT03671122.

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

Abstract Aims In the heart failure (HF) with preserved ejection fraction (HFpEF) PARAGON‐HF trial, sacubitril/valsartan vs. valsartan improved mortality/morbidity in patients with left ventricular ejection fraction (LVEF) below median (57%). We assessed eligibility for sacubitril/valsartan based on four scenarios. Methods and results Eligibility was assessed in the Karolinska‐Rennes study (acute HFpEF, LVEF ≥ 45%, and N‐terminal pro‐B‐type natriuretic peptide ≥300 pg/mL subsequently assessed as outpatients including echocardiography) in (i) a trial scenario (all trial criteria); (ii) a pragmatic scenario (selected trial criteria); (iii) LVEF below lower limit of normal range (

Abstract Aims Heart failure (HF) with preserved ejection fraction (HFpEF) has poor long‐term prognosis. We assessed rates and predictors of outcome 10 years after an acute episode of HF. Methods and results The Karolinska‐Rennes (KaRen) study enrolled HFpEF patients with acute HF, ejection fraction ≥ 45%, and N‐terminal pro‐brain natriuretic peptide > 300 ng/L in 2007–11. Clinical data were collected at enrolment and after 4–8 weeks including detailed echocardiography. Follow‐up data were collected 10 years after study initiation, starting from 6 months after enrolment until 2018 assessed by telephone. Independent predictors of primary (all‐cause mortality or HF hospitalization) and secondary (all‐cause mortality) outcomes were assessed by multivariable Cox regression. Of 539 patients, long‐term follow‐up data were available for 397 patients [52% female; median (interquartile range) age 79 (73, 84) years]. Over a follow‐up of 5.44 (2.06–7.89) years, 1, 3, 5, and 10 year mortality rates were 15%, 31%, 47%, and 74%, respectively, with an incidence rate of 130/1000 patient‐years. The primary outcome was met in 84% of the population, with an incidence rate of 227/1000 patient‐years. The independent predictors of the primary outcome were tricuspid regurgitation peak velocity (m/s) [hazard ratio 1.87 (1.34–2.62)], diabetes mellitus [1.75 (1.11–2.74)], and cancer [1.75 (1.01–3.03)] while female sex was associated with reduced risk [0.64 (0.41–0.98)]. Conclusions In HFpEF, 1, 3, 5, and 10 year mortality was 15%, 31%, 47%, and 74% and mortality or first HF hospitalization was 35%, 54%, 67%, and 84%, respectively. Independent predictors of mortality or HF hospitalization were tricuspid regurgitation peak velocity, diabetes mellitus, cancer, and male sex. In clinical management of HFpEF, attention should be paid to both cardiac and non‐cardiac conditions.

AimsExtracellular vesicles (EVs) were investigated as potential biomarkers associated with heart failure (HF) pathophysiology in patients undergoing elective coronary artery bypass surgery characterized by HF phenotype.Materials and methodsPatients with preoperative proxy-diagnoses of HF types i.e., preserved (HFpEF; n = 19) or reduced ejection fraction (HFrEF; n = 20) were studied and compared to patients with normal left ventricular function (n = 42). EVs in plasma samples collected from the coronary sinus, an arterial line, and from the right atrium were analyzed by flow cytometry. We studied EVs of presumed cardiomyocyte origin [EVs exposing Connexin-43 + Caveolin-3 (Con43 + Cav3) and Connexin-43 + Troponin T (Con43 + TnT)], of endothelial origin [EVs exposing VE-Cadherin (VE-Cad)] and EVs exposing inflammatory markers [myeloperoxidase (MPO) or pentraxin3 (PTX3)].ResultsMedian concentrations of EVs exposing Con43 + TnT and Con43 + Cav3 were approximately five to six times higher in coronary sinus compared to radial artery indicative of cardiac release. Patients with HFrEF had high trans-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas HFpEF had elevated gradients of Con43 + Cav3 EVs but lower gradients of Con43 + TnT. Coronary sinus concentrations of both Con43 + TnT and Con43 + Cav3 correlated significantly with echocardiographic and laboratory measures of HF. MPO-EV concentrations were around two times higher in the right atrium compared to the coronary sinus, and slightly higher in HFpEF than in HFrEF. EV concentrations of endothelial origin (VE-Cad) were similar in all three patient groups.ConclusionCon43 + TnT and Con43 + Cav3 EVs are released over the heart indicating cardiomyocyte origin. In HFrEF the EV release profile is indicative of myocardial injury and myocardial stress with elevated trans-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas in HFpEF the profile indicates myocardial stress with less myocardial injury.

Abstract Aims Echocardiographic predictors of outcomes in heart failure with preserved ejection fraction (HFpEF) have not been systematically or independently validated. We aimed at identifying echocardiographic predictors of cardiovascular events in a large cohort of patients with HFpEF and to validate these in an independent large cohort. Methods and results We assessed the association between echocardiographic parameters and cardiovascular outcomes in 515 patients with heart failure with preserved left ventricular (LV) ejection fraction (>50%) in the MEtabolic Road to DIAstolic Heart Failure (MEDIA) multicentre study. We validated out findings in 286 patients from the Karolinska‐Rennes Prospective Study of HFpEF (KaRen). After multiple adjustments including N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), the significant predictors of death or cardiovascular hospitalization were pulmonary arterial systolic pressure > 40 mmHg, respiratory variation in inferior vena cava diameter > 0.5, E/e' > 9, and lateral mitral annular s' 35% 1 year risk. Adding these four echocardiographic variables on top of clinical variables and NT‐proBNP yielded significant net reclassification improvement (33.8%, P

Objective: Cardiac resynchronization therapy (CRT) has been shown to reduce mortality in selected patients with heart failure with reduced ejection fraction (HFrEF). CRT Survey-II was a snapshot survey to assess current clinical practice with regard to CRT. Herein, we aimed to compare Turkish data with other countries of European Society of Cardiology (ESC). Methods: The survey was conducted between October 2015 and December 2016 in 42 ESC member countries. All consecutive patients who underwent a de novo CRT implantation or a CRT upgrade were eligible. Results: A total of 288 centers included 11,088 patients. From Turkey, 16 centers recruited 424 patients representing 12.9% of all implantations. Compared to the entire cohort, Turkish patients were younger with a lower proportion of men and a higher proportion with ischemic etiology. Electrocardiography (ECG) showed sinus rhythm in 81.5%, a QRS duration of

Abstract Aims In heart failure (HF) with preserved ejection fraction (HFpEF), microvascular inflammation is proposed as an underlying mechanism. Myeloperoxidase (MPO) is associated with vascular dysfunction and prognosis in congestive HF. Methods and results MPO, MPO‐related biomarkers, and echocardiography were assessed in 86 patients, 4–8 weeks after presentation with acute HF (EF ≥ 45%), and in 46 healthy controls. Patients were followed up for median 579 days (Q1;Q3 276;1178) regarding the composite endpoint all‐cause mortality or HF hospitalization. Patients were 73 years old, 51% were female, EF was 64% (Q1;Q3 58;68), E/e′ was ratio 10.8 (8.3;14.0), and left atrial volume index (LAVI) was 43 mL/m2 (38;52). Controls were 60 (57;62) years old (vs. patients; P 14, uric acid and SDMA were elevated (421 vs. 344 μM, P = 0.012; 0.54 vs. 0.47 μM, P = 0.039, respectively), and MPO was 121 vs. 98 ng/mL (P = 0.090). The ratios of arginine/ADMA (112 vs. 162; P

Abstract Aims Despite evidence‐based therapeutic approaches, target blood pressure is obtained by less than half of patients with hypertension. Hypertension is associated with a significant risk for heart failure, in particular heart failure with preserved left ventricular (LV) ejection fraction (HFpEF). Although treatment is suggested to be given early after hypertension diagnosis, there is still no evidence‐based medical treatment for HFpEF. We aim to study the underlying mechanisms behind the transition from uncomplicated hypertension to hypertensive heart disease (HHD) and HFpEF. To this end, we will combine cardiac imaging techniques and measurements of circulating fibrosis markers to longitudinally monitor fibrosis development in patients with hypertension. Methods and results In a prospective cohort study, 250 patients with primary hypertension and 60 healthy controls will be characterized at inclusion and after 1 and 6 years. Doppler echocardiography, cardiac magnetic resonance imaging, and electrocardiogram will be used for measures of cardiac structure and function over time. Blood biomarkers reflecting myocardial fibrosis, inflammation, and endothelial dysfunction will be analysed. As a proxy for HFpEF development, the primary endpoint is to measure echocardiographic changes in LV function and structure (E/e′ and LAVI) and to relate these measures of LV filling to blood pressure, biomarkers, electrocardiogram, and cardiac magnetic resonance. Conclusions We aim to study the timeline and transition from uncomplicated hypertension to HHD and HFpEF. In order to identify subjects prone to develop HHD and HFpEF, we want to find biomarkers and cardiac imaging variables to explain disease progression. Ultimately, we aim at finding new pathways to prevent HFpEF.

Abstract Aims Neuregulin1‐β (NRG1‐β) is released from microvascular endothelial cells in response to inflammation with compensatory cardioprotective effects. Circulating NRG1‐β is elevated in heart failure (HF) with reduced ejection fraction (HFrEF) but not studied in HF with preserved EF (HFpEF). Methods and results Circulating NRG1‐β was quantified in 86 stable patients with HFpEF (EF ≥45% and N‐terminal pro‐brain natriuretic peptide >300 ng/L), in 86 patients with HFrEF prior to and after left ventricular assist device (LVAD) and/or heart transplantation (HTx) and in 21 healthy controls. Association between NRG1‐β and the composite outcome of all‐cause mortality/HF hospitalization in HFpEF and all‐cause mortality/HTx/LVAD implantation in HFrEF with and without ischaemia assessed as macrovascular coronary artery disease was assessed. In HFpEF, median (25th–75th percentile) NRG1‐β was 6.5 (2.1–11.3) ng/mL; in HFrEF, 3.6 (2.1–7.6) ng/mL (P = 0.035); after LVAD, 1.7 (0.9–3.6) ng/mL; after HTx 2.1 (1.4–3.6) ng/mL (overall P < 0.001); and in controls, 29.0 (23.1–34.3) ng/mL (P = 0.001). In HFrEF, higher NRG1‐β was associated with worse outcomes (hazard ratio per log increase 1.45, 95% confidence interval 1.04–2.03, P = 0.029), regardless of ischaemia. In HFpEF, the association of NRG1‐β with outcomes was modified by ischaemia (log‐rank P = 0.020; Pinteraction = 0.553) such that only in ischaemic patients, higher NRG1‐β was related to worse outcomes. In contrast, in patients without ischaemia, higher NRG1‐β trended towards better outcomes (hazard ratio 0.71, 95% confidence interval 0.48–1.05, P = 0.085). Conclusions Neuregulin1‐β was reduced in HFpEF and further reduced in HFrEF. The opposing relationships of NRG1‐β with outcomes in non‐ischaemic HFpEF compared with HFrEF and ischaemic HFpEF may indicate compensatory increases of cardioprotective NRG1‐β from microvascular endothelial dysfunction in the former (non‐ischaemic HFpEF), but this compensatory mechanism is overwhelmed by the presence of ischaemia in the latter (HFrEF and ischaemic HFpEF).

Abstract Aims This study aims to assess prognostic impact of Framingham criteria for heart failure (FC‐HF) in patients with stable heart failure (HF) with preserved ejection fraction (HFpEF). Methods and results In the prospective Karolinska‐Rennes (KaRen) study, we assessed stable HFpEF patients after an acute HF episode. We evaluated associations between the four descriptive models of HFpEF and the composite endpoint of all‐cause mortality and HF hospitalization. The descriptive models were FC‐HF alone, FC‐HF + natriuretic peptides (NPs) according to the PARAGON trial, FC‐HF + NPs + echocardiographic HFpEF criteria according to European Society of Cardiology HF guidelines, and FC‐HF + NPs + echocardiographic criteria according to the PARAGON trial. Out of the 539 patients enrolled in KaRen, 438 returned for the stable state revisit after 4–8 weeks, 13 (2.4%) patients died before the planned follow‐up, and 88 patients (16%) declined or were unable to return. Three hundred ninety‐nine patients have FC registered at follow‐up, and among these, the four descriptive models were met in 107 (27%), 82 (22%), 61 (21%), and 69 (22%) patients, and not met in 292 (73%). The 107 patients that had FC‐HF at stable state (descriptive model 1) could also be part of the other models because all patients in models 1–4 had to fulfil the FC‐HF. The patients in model 0 did not fulfil the criteria for FC‐HF but could have single FC. Of single FC, only pleural effusion predicted the endpoint [hazard ratio (HR) 3.38, 95% confidence interval (CI) 1.47–7.76, P = 0.004]. Patients without FC‐HF had better prognosis than patients meeting FC‐HF. The unadjusted associations between the four HFpEF descriptive models and the endpoint were HR 1.54, 95% CI 1.14–2.09, P = 0.005; HR 1.71, 95% CI 1.24–2.36, P = 0.002; HR 1.95, 95% CI 1.36–2.81, P = 0.001; and HR 2.05, 95% CI 1.45–2.91, P

Background: Office blood pressure (OBP) is used for diagnosing and treating hypertension but ambulatory blood pressure measurement (ABPM) associates more accurately with patient outcome. BP control is important in secondary prevention but it is unknown whether the use of APBM improves BP-control in this setting. Our objective was to investigate whether physician awareness of ABP after percutaneous coronary intervention (PCI) improved BP-control. Methods: A total of 200 patients performed ABPM before and after their PCI follow-up visit. Patients were randomized to open (O) or concealed (C) ABPM results for the physician at the follow-up visit. The change in ABP and antihypertensive medication in relation to baseline ABP was compared between the two groups. Results: The average OBP (O and C: 128/76 mmHg) and ABP (O: 123/73 mmHg, C: 127/74 mmHg) was well controlled and did not change between the first and second measurement. A slight increase in systolic ABP during night time was observed in the open arm compared to the concealed arm. Among patients with high ABP (>130/80 mm Hg) at baseline more patients in the C compared to O group remained with a high ABP at the end of study 34/44 (77%) vs 19/34 (56%), p = 0.045. There was a positive correlation between baseline systolic ABP and ABP change in both the O (r = 0.41, p

Abstract Background People with chronic kidney disease (CKD) are at an increased risk of developing hyperkalaemia due to their declining kidney function. In addition, these patients are often required to reduce or discontinue guideline-recommended renin-angiotensin-aldosterone system inhibitor (RAASi) therapy due to increased risk of hyperkalaemia. This original research developed a model to quantify the health and economic benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD. Methods A patient-level simulation model was designed to fully characterise the natural history of CKD over a lifetime horizon, and predict the associations between serum potassium levels, RAASi use and long-term outcomes based on published literature. The clinical and economic benefits of maintaining sustained potassium levels and therefore avoiding RAASi discontinuation in CKD patients were demonstrated using illustrative, sensitivity and scenario analyses. Results Internal and external validation exercises confirmed the predictive capability of the model. Sustained potassium management and ongoing RAASi therapy were associated with longer life expectancy (+ 2.36 years), delayed onset of end stage renal disease (+ 5.4 years), quality-adjusted life-year gains (+ 1.02 QALYs), cost savings (£3135) and associated net monetary benefit (£23,446 at £20,000 per QALY gained) compared to an absence of RAASi to prevent hyperkalaemia. Conclusion This model represents a novel approach to predicting the long-term benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD, irrespective of the strategy used to achieve this target, which may support decision making in healthcare.

Abstract Background To address a current paucity of European data, this study developed equations to predict risks of mortality, major adverse cardiac events (MACE) and renin angiotensin-aldosterone system inhibitor (RAASi) discontinuation using time-varying serum potassium and other covariates, in a UK cohort of chronic kidney disease (CKD) patients. Methods This was a retrospective observational study of adult CKD patients listed on the Clinical Practice Research Datalink, with a first record of CKD (stage 3a–5, pre-dialysis) between 2006 and 2015. Patients with heart failure at index were excluded. Risk equations developed using Poisson Generalized Estimating Equations were utilised to estimate adjusted incident rate ratios (IRRs) between serum potassium and adverse outcomes, and identify other predictive clinical factors. Results Among 191,964 eligible CKD patients, 86,691 (45.16%), 30,629 (15.96%) and 9440 (4.92%) experienced at least one hyperkalaemia episode, when defined using serum potassium concentrations 5.0–

2016 ESC GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF ACUTE AND CHRONIC HEART FAILURE.The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC).Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

Background Dosing of renin–angiotensin–aldosterone system inhibitors (RAASi) may be modified to manage associated hyperkalemia risk; however, this approach could adversely affect cardiorenal outcomes. This study investigated real‐world associations of RAASi dose, hyperkalemia, and adverse clinical outcomes in a large cohort of UK cardiorenal patients. Methods and Results This observational study included RAASi‐prescribed patients with new‐onset chronic kidney disease (n=100 572) or heart failure (n=13 113) first recorded between January 2006 and December 2015 in Clinical Practice Research Datalink and linked Hospital Episode Statistics databases. Odds ratios associating hyperkalemia and RAASi dose modification were estimated using logistic generalized estimating equations with normal (

AIM: Between October 2015 and December 2016, 11,088 patients from 42 countries having cardiac resynchronisation therapy (CRT) devices implanted were included in the CRT II Survey. We compared the characteristics of Swiss CRT recipients with the overall European population. METHODS Demographic and procedural data from seven Swiss centres recruiting all consecutive patients undergoing either de-novo CRT implantation or an upgrade to a CRT system were collected and compared with the European population. RESULTS A total of 320 Swiss patients (24.4% female, mean age 71.0 ± 10.2 years, 47% ischaemic cardiomyopathy) were enrolled, which amounts to 38% of all CRT implantations in Switzerland during this period. Of the patients enrolled, 38% had atrial fibrillation, 27% second- or third-degree atrioventricular block, and 68% complete left bundle-branch block. Swiss patients had significantly less often the classical indication of heart failure with a wide QRS complex (40 vs 61%; odds ratio [OR] 0.44, 95% confidence interval [CI] 0.35–0.55; p

Aims. The Cardiac Resynchronization Therapy (CRT) Survey II was conducted between October 2015 and December 2016 and included data from 11088 CRT implantations from 42 countries. The survey’s aim was to report on current European CRT practice. The aim of this study was to compare the Croatian national CRT practice with the European data. Methods. Five centres from Croatia recruited consecutive patients, in a 15-month period, who underwent CRT implantation, primary or an upgrade. Data were collected prospectively by using online database. Results. A total of 115 patients were included in Croatia, which is 33.2% of all CRT implants in Croatia during the study period (total n=346). Median age of the study population was 67 (61–73) years, and 21.2% were women. Primary heart failure (HF) aetiology was nonischemic in 61.1% of patients, and HF with wide QRS was the most common indication for the implantation (73.5%). 80% of patients had complete left bundle branch block, and over two-third had QRS ≥150 ms. Device-related adverse events were recorded in 4.3% of patients. When compared with European countries, Croatian patients were significantly younger (67 vs. 70 years, p=0.012), had similar rate of comorbidities with the exception of higher prevalence of hypertension. Croatian patients significantly more often received CRT-pacemaker when compared with European population (58.3 vs. 29.9%, OR 3.27, 95%CI 2.25–4.74, p