Association of epicardial adipose tissue with proteomics, coronary flow reserve, cardiac structure and function, and quality of life in heart failure with preserved ejection fraction: insights from the PROMIS-HFpEF study.

AIM: Epicardial adipose tissue (EAT) may play a role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). We investigated associations of EAT with proteomics, coronary flow reserve (CFR), cardiac structure and function, and quality of life (QoL) in the prospective multinational PROMIS-HFpEF cohort. METHODS AND RESULTS: Epicardial adipose tissue was measured by echocardiography in 182 patients and defined as increased if ≥9 mm. Proteins were measured using high-throughput proximity extension assays. Microvascular dysfunction was evaluated with Doppler-based CFR, cardiac structural and functional indices with echocardiography and QoL by Kansas City Cardiomyopathy Questionnaire (KCCQ). Patients with increased EAT (n = 54; 30%) had higher body mass index (32 [28-40] vs. 27 [23-30] kg/m2 ; p < 0.001), lower N-terminal pro-B-type natriuretic peptide (466 [193-1133] vs. 1120 [494-1990] pg/ml; p < 0.001), smaller indexed left ventricular (LV) end-diastolic and left atrial (LA) volumes and tendency to lower KCCQ score. Non-indexed LV/LA volumes did not differ between groups. When adjusted for body mass index, EAT remained associated with LV septal wall thickness (coefficient 1.02, 95% confidence interval [CI] 1.00-1.04; p = 0.018) and mitral E wave deceleration time (coefficient 1.03, 95% CI 1.01-1.05; p = 0.005). Increased EAT was associated with proteomic markers of adipose biology and inflammation, insulin resistance, endothelial dysfunction, and dyslipidaemia but not significantly with CFR. CONCLUSION: Increased EAT was associated with cardiac structural alterations and proteins expressing adiposity, inflammation, lower insulin sensitivity and endothelial dysfunction related to HFpEF pathology, probably driven by general obesity. Potential local mechanical or paracrine effects mediated by EAT remain to be elucidated.

Left atrial reservoir strain improves diagnostic accuracy of the 2016 ASE/EACVI diastolic algorithm in patients with preserved left ventricular ejection fraction: insights from the KARUM haemodynamic database.

AIMS: This study aimed to investigate the incremental value offered by left atrial reservoir strain (LASr) to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) diastolic algorithm to identify elevated left ventricular (LV) filling pressure in patients with preserved ejection fraction (EF). METHODS AND RESULTS: Near-simultaneous echocardiography and right heart catheterization were performed in 210 patients with EF ≥50% in a large, dual-centre study. Elevated filling pressure was defined as invasive pulmonary capillary wedge pressure (PCWP) ≥15 mmHg. LASr was evaluated using speckle-tracking echocardiography. Diagnostic performance of the ASE/EACVI diastolic algorithm was validated against invasive reference and compared with modified algorithms incorporating LASr. Modest correlation was observed between E/e', E/A ratio, and LA volume index with PCWP (r = 0.46, 0.46, and 0.36, respectively; P < 0.001 for all). Mitral e' and TR peak velocity showed no association. The ASE/EACVI algorithm (89% feasibility, 71% sensitivity, 68% specificity) demonstrated reasonable ability (AUC = 0.69) and 68% accuracy to identify elevated LV filling pressure. LASr displayed strong ability to identify elevated PCWP (AUC = 0.76). Substituting TR peak velocity for LASr in the algorithm (69% sensitivity, 84% specificity) resulted in 91% feasibility, 81% accuracy, and stronger agreement with invasive measurements. Employing LASr as per expert consensus (71% sensitivity, 70% specificity) and adding LASr to conventional parameters (67% sensitivity, 84% specificity) also demonstrated greater feasibility (98% and 90%, respectively) and overall accuracy (70% and 80%, respectively) to estimate elevated PCWP. CONCLUSIONS: LASr improves feasibility and overall accuracy of the ASE/EACVI algorithm to discern elevated filling pressures in patients with preserved EF.

Accuracy and diagnostic performance of doppler echocardiography to estimate mean pulmonary artery pressure in heart failure.

BACKGROUND: Multiple echocardiographic algorithms have been proposed to estimate mean pulmonary artery pressure (PAPM ) and assess pulmonary hypertension (PH) likelihood. We assessed the accuracy of four echocardiographic approaches to estimate PAPM in heart failure (HF) patients undergoing near-simultaneous right heart catheterization (RHC), and compared diagnostic performance to identify PH with recommendation-advised tricuspid regurgitation peak velocity (TRVmax ). METHODS: We employed four validated echocardiographic algorithms incorporating tricuspid regurgitation peak or mean gradient, pulmonary regurgitation peak gradient, and right ventricular outflow tract acceleration time to estimate PAPM . Echocardiographic estimates of right atrial pressure were incorporated in all algorithms but one. Association and agreement with invasive PAPM were assessed. Diagnostic performance of all algorithms to identify PH was evaluated and compared with the recommended TRVmax cut-off. RESULTS: In 112 HF patients, all echocardiographic algorithms demonstrated reasonable association (r = .41-.65; p < 0.001) and good agreement with invasive PAPM , with relatively lower mean bias and higher precision observed in algorithms that incorporated tricuspid regurgitation peak or mean gradient. All methods demonstrated strong ability to identify PH (AUC = .70-.80; p < 0.001) but did not outperform TRVmax (AUC = .84; p < 0.001). Echocardiographic estimates of right atrial pressure were falsely elevated in 30% of patients. CONCLUSIONS: Echocardiographic estimates demonstrate reasonable association with invasive PAPM and strong ability to identify PH in HF. However, none of the algorithms outperformed recommendation-advised TRVmax . The incremental value of echocardiographic estimates of right atrial pressure may need to be re-evaluated.

Disproportionate left atrial myopathy in heart failure with preserved ejection fraction among participants of the PROMIS-HFpEF study.

Impaired left atrial (LA) function in heart failure with preserved ejection fraction (HFpEF) is associated with adverse outcomes. A subgroup of HFpEF may have LA myopathy out of proportion to left ventricular (LV) dysfunction; therefore, we sought to characterize HFpEF patients with disproportionate LA myopathy. In the prospective, multicenter, Prevalence of Microvascular Dysfunction in HFpEF study, we defined disproportionate LA myopathy based on degree of LA reservoir strain abnormality in relation to LV myopathy (LV global longitudinal strain [GLS]) by calculating the residuals from a linear regression of LA reservoir strain and LV GLS. We evaluated associations of disproportionate LA myopathy with hemodynamics and performed a plasma proteomic analysis to identify proteins associated with disproportionate LA myopathy; proteins were validated in an independent sample. Disproportionate LA myopathy correlated with better LV diastolic function but was associated with lower stroke volume reserve after passive leg raise independent of atrial fibrillation (AF). Additionally, disproportionate LA myopathy was associated with higher pulmonary artery systolic pressure, higher pulmonary vascular resistance, and lower coronary flow reserve. Of 248 proteins, we identified and validated 5 proteins (involved in cardiomyocyte stretch, extracellular matrix remodeling, and inflammation) that were associated with disproportionate LA myopathy independent of AF. In HFpEF, LA myopathy may exist out of proportion to LV myopathy. Disproportionate LA myopathy is a distinct HFpEF subtype associated with worse hemodynamics and a distinct proteomic signature, independent of AF.

Diagnostic utility of right atrial reservoir strain to identify elevated right atrial pressure in heart failure.

BACKGROUND: Accurate non-invasive estimation of right atrial pressure (RAP) is essential to assess volume status and optimize therapy in heart failure (HF). This study aimed to evaluate the utility of right atrial reservoir strain (RASr) assessed by speckle-tracking echocardiography to identify elevated RAP in HF and compare diagnostic performance with estimated RAP employing inferior vena cava size and collapsibility (RAPIVC), in addition to RA area. METHOD: Association between RASr and invasive RAP (RAPInvasive) was examined in 103 HF subjects that underwent standard echocardiography with speckle-tracking strain analysis directly followed by right heart catheterization. The discriminatory ability of RASr to identify RAPInvasive > 7 mmHg was evaluated and compared with RAPIVC and RA area. RESULTS: RASr demonstrated association with RAPInvasive (ß = -0.41, p < 0.001) and was an independent predictor when adjusted for potential confounders (ß = -0.25, p < 0.001). Further, RASr showcased strong discriminatory ability to identify subjects with RAPInvasive > 7 mmHg (AUC = 0.78; 95% CI 0.68-0.87; p < 0.001). At a cut-off value of -15%, RASr displayed 78% sensitivity and 72% specificity to identify elevated RAPInvasive. In comparison, RAPIVC (AUC = 0.71; 95% CI 0.61-0.81; p < 0.001) demonstrated 89% sensitivity and 32% specificity with high false positive rate. RA area (AUC = 0.66; 95% CI 0.55-0.76, p = 0.005) displayed 64% sensitivity and 53% specificity. CONCLUSIONS: RASr demonstrates good ability to identify elevated RAP and relatively stronger diagnostic performance when compared with conventional non-invasive measures. RASr may be useful as a novel noninvasive estimate of RAP in HF management.

Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study.

BACKGROUND: Coronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF. METHODS AND RESULTS: We assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54-159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0-68, P = .023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization. CONCLUSIONS: In this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV- and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.

Heart Failure in Patients Undergoing Elective and Emergency Noncardiac Surgery: Still a Poorly Addressed Risk Factor.

BACKGROUND: Noncardiac surgery is increasingly offered to an older, more comorbid population. The aim was to characterize patients with the diagnosis of heart failure (HF) undergoing elective and emergency noncardiac surgery in a broad, contemporary Swedish cohort, and to assess the short- and long-term mortality in patients with HF as compared with patients without HF. METHODS AND RESULTS: Data from 200,638 and 97,129 patients undergoing elective and emergency surgical procedures at 23 Swedish university, county, and district hospitals during 2007 to 2013 were analyzed through linkage of the surgical Orbit Database to the National Patient and the Cause of Death registries. In total 7212 patients (3.6%) with a diagnosis of HF before surgery underwent elective and 6455 patients (6.6%) underwent emergency surgery. Patients with HF were older had more comorbidities, and higher mortality than patients without HF. Crude and adjusted risk ratios for 30-day mortality after elective surgery were 5.36 (95% confidence interval [CI] 4.67-6.16) and 1.79 (95% CI 1.50-2.14) (adjusted for comorbidities, surgical risk level, age, and sex). Corresponding data for emergency surgery was 3.84 (95% CI 3.58-4.12) and 1.48 (95% CI 1.31-1.62). Mortality in patients with HF after elective surgery at 30 days, 90 days, and 1 year was 3.2%, 6.5%, and 16.2% and after emergency surgery it was 13.7%, 22.4%, and 39.3%. CONCLUSIONS: Patients with HF undergoing elective or emergency noncardiac surgery in a modern surgical setting have a substantial mortality risk and HF is both a risk factor and a strong marker for increasd risk. The reasons for the high mortality are not well-understood and warrant further attention.

Sex-Based Differences in Heart Failure Across the Ejection Fraction Spectrum: Phenotyping, and Prognostic and Therapeutic Implications.

OBJECTIVES: This study assessed sex-related differences in a large cohort of unselected patients with heart failure (HF) across the ejection fraction (EF) spectrum. BACKGROUND: Females are under-represented in randomized clinical trials. Potential sex-related differences in HF may question the generalizability of trials. METHODS: In the Swedish Heart Failure Registry population multivariate Cox and logistic regression models were fitted to investigate differences in prognosis, prognostic predictors, and treatments across males and females. RESULTS: Of 42,987 patients, 37% were females (55% with HF with preserved EF [HFpEF], 39% with HF with mid-range EF [HFmrEF], and 29% with HF with reduced EF [HFrEF]). Females were older and more symptomatic and more likely to have hypertension and kidney disease but less likely to have diabetes and ischemic heart disease. After adjustments, females were more likely to use beta-blockers and digoxin but less likely to receive HF device therapy. Crude mortality/HF hospitalization rates for HFpEF (hazard ratio [HR]: 1.16) and HFmrEF (HR: 1.14) were significantly higher in females but lower in females with HFrEF (HR: 0.95). After adjustments, the risk was significantly lower in females regardless of EF (HR: 0.80 in HFrEF, HR: 0.91 in HFmrEF, and HR: 0.93 in HFpEF). The main sex-related differences in prognostic predictors concerned diabetes in HFrEF and anemia in HFmrEF. CONCLUSIONS: Males and females with HF showed different characteristics across the EF spectrum. Males reported a lower crude risk of mortality/morbidity in HFpEF and HFmrEF but higher risk of HFrEF, although after adjustments, prognosis was better in females regardless of EF. The observed sex-related differences highlight the need for an adequate representation of females in HF randomized controlled trials to improve generalizability.

N-terminal pro-B-type natriuretic peptide in chronic heart failure: The impact of sex across the ejection fraction spectrum.

OBJECTIVE: The aim was to assess sex-specific differences in N-terminal B-type natriuretic peptide (NT-proBNP) regarding concentrations, predictors of high concentrations, and prognostic role, in a large and unselected population with chronic heart failure (HF) with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF). METHODS AND RESULTS: In 9847 outpatients with HFpEF, HFmrEF, and HFrEF (49 vs. 35 vs. 25% females, respectively) from the Swedish HF Registry, median NT-proBNP concentrations were 1598 ng/L in females vs. 1310 ng/L in males in HFpEF, 1764 vs. 1464 ng/L in HFmrEF, and 2543 vs. 2226 ng/L in HFrEF (p < 0.05 for all). The differences persisted after multiple adjustment. The largest sex-difference in NT-proBNP levels was observed in HFpEF with sinus rhythm, where median concentrations were 1.4 folds higher in females (923 vs. 647 ng/L). Independent predictors of NT-proBNP levels (defined as above the different medians according to sex and HF phenotype) were overall consistent across sexes and EF. NT-proBNP levels were similarly associated with risk of all-cause death/HF hospitalization in both sexes regardless of EF. CONCLUSION: Concentrations of NT-proBNP were higher in females across the EF spectrum, with larger relative differences in HFpEF with sinus rhythm. However, similar predictors of high levels were observed in both sexes. There were no sex-differences in the prognostic role of NT-proBNP. These findings support the use of NT-proBNP for prognostic purposes in chronic HF, regardless of sex.

ST2 in heart failure with preserved and reduced ejection fraction.

OBJECTIVES: Soluble suppression of tumorigenecity 2 (sST2) is prognostic in acute and chronic heart failure with reduced ejection fraction (HFrEF) but less studied in HF with preserved EF (HFpEF). We evaluated sST2 concentrations, correlations with biomarkers and echocardiographic measures of diastolic and systolic function, and associations with outcomes in HFpEF and HFrEF. DESIGN AND RESULTS: A total of 193 subjects from three different cohorts were included. Eighty-six HFpEF patients were obtained from the Karolinska Rennes (KaRen) study, 86 patients with HFrEF were recruited from referrals to Karolinska University Hospital for advanced assessment of HF, and 21 controls were included (ClinicalTrials.gov Identifier for KaRen: NCT01091467). HFrEF and controls cohorts did not have ClinicalTrials.gov registrations. sST2 was lower in HFpEF, median (interquartile range); 23 (17-31) compared to HFrEF; 35 (23-52) µg/L, p < .001. In both HFpEF and HFrEF, sST2 correlated positively with NT-proBNP (HFpEF rs=0.392, p < .001 and HFrEF rs=0.466, p < .001). In HFpEF, sST2 correlated to left atrial volume index (rs=0.276, p = .019) but not to E/E´, nor to left ventricular mass index. sST2 was in HFpEF associated with the composite endpoint of death or HF hospitalization, adjusted hazard ratio (HR) per log increase in sST2 6.62, 95% confidence interval (CI) 1.04-42.28, p = .046, and in HFrEF death, heart transplant or left ventricular assist systems; 3.51, 95% CI 1.05-11.69, p = .041. CONCLUSIONS: In patients with HFpEF compared to HFrEF, crude levels of sST2 were lower but potentially more strongly associated with outcomes. The lower levels of sST2 in HFpEF than in HFrEF may reflect lower degrees of fibrosis, but the potentially stronger association with outcomes may reflect a greater prognostic importance of progressive fibrosis and as such a greater potential for intervention. In conclusion; this study adds to the evidence of sST2 as prognostic marker in both HFpEF and HFrEF.

Cardiogenic shock triggered by phaeochromocytoma crisis after an oral glucose tolerance test: a case report.

BACKGROUND: Phaeochromocytomas are rare catecholamine-producing tumours which typically present with comparatively benign symptoms such as headache, palpitations, sweating, hypertension, and insulin resistance. In rare cases, severe cardiac manifestations have been reported. We describe a patient who developed severe hypoglycaemia after an oral glucose tolerance test (OGTT), potentially triggering a phaeochromocytoma crisis and cardiogenic shock. To the best of our knowledge, only four other cases of hypoglycaemia after OGTT have been reported in patients with phaeochromocytoma, of which none developed a phaeochromocytoma crisis. CASE SUMMARY: A 53-year-old woman with hypertension, dyslipidaemia, and prediabetes presented to the Emergency Department with hypoxia, hyperglycaemia, lactic acidosis, severe left ventricular dysfunction, and pulmonary oedema followed by cardiogenic shock. Onset of symptoms was only few hours after an OGTT during which she had developed severe transient hypoglycaemia. Angiography was performed due to elevated troponin levels and showed a midventricular contraction pattern typical of takotsubo. This was subsequently confirmed by cardiac magnetic resonance imaging. The patient's condition improved during the first 36 h and she was discharged home on Day 7. A positive catecholamine test prompted readmission to the Endocrinology Unit, where computer tomography confirmed the diagnosis of phaeochromocytoma. An adrenalectomy was performed, and the diagnosis was verified histopathologically. DISCUSSION: The possibility of a phaeochromocytoma must be considered as a potential triggering factor in patients presenting with takotsubo cardiomyopathy, in particular, when blood glucose levels fluctuate between severe hypo- and hyperglycaemia.

Patient reported outcome in HFpEF: Sex-specific differences in quality of life and association with outcome.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is associated with poor quality of life (QoL), or patient reported outcome (PRO). Despite female predominance in HFpEF, sex-specific differences in PROs remain poorly studied. We assessed PRO measures and their association with HF-severity and outcome in HFpEF by sex. METHODS AND RESULTS: In 378 patients with HFpEF from the KaRen study, EQ-5D-3L® and Minnesota Living with Heart Failure Questionnaire® (MLHFQ) were assessed. Characteristics and comorbidities were largely similar in women (n = 212, 57%) and men. Women expressed worse QoL in EQ-5D-3L®(EQ-VAS), independent of age and HF-severity, mean (SD), 57 (20) vs. 61 (19), p = 0.010. There was no difference in MLHFQ, 31 (21) vs. 29 (21), p = 0.269. Spearman's correlations with HF-severity (NYHA-class) were for MLHFQ in women rs 0.37 vs. men 0.41, p for both <0.001, and for EQ-VAS rs -0.28, p = 0.001 vs. -0.45, p < 0.001. Correlations with natriuretic peptides were for MLHFQ rs 0.21, p = 0.003 in women vs. men 0.27, p < 0.001, and for EQ-VAS rs -0.17 vs. -0.27, p both < 0.001. Associations between PRO and the composite of HF hospitalisation or all-cause death were present in men only, adjusted HR per 5 units increase in MLHFQ 1.06, 95% confidence interval (CI) 1.01-1.11, p = 0.02 and EQ-VAS, HR 0.93, 95% CI 0.88-0.98, p = 0.010. CONCLUSION: In HFpEF, women had worse general but similar disease specific QoL compared to men. QoL was more strongly associated with HF-severity in men, and associated with outcomes only in men. In women with HFpEF, QoL appears less determined by HF itself and potentially more by other unknown factors.

HFpEF and HFrEF Display Different Phenotypes as Assessed by IGF-1 and IGFBP-1.

BACKGROUND: Anabolic drive is impaired in heart failure with reduced ejection fraction (HFrEF) but insufficiently studied in heart failure with preserved ejection fraction (HFpEF). Insulin-like growth factor 1 (IGF-1) mediates growth hormone effects and IGF binding protein 1 (IGFBP-1) regulates IGF-1 activity. We tested the hypothesis that HFpEF and HFrEF are similar with regard to IGF-1 and IGFBP-1. METHODS AND RESULTS: In patients with HFpEF (n = 79), HFrEF (n = 85), and controls (n = 136), we analyzed serum IGF-1 and IGFBP-1 concentrations, correlations, and associations with outcome. Age-standardized scores of IGF-1 were higher in HFpEF, median arbitrary units (interquartile range); 1.21 (0.57-1.96) vs HFrEF, 0.09 (-1.40-1.62), and controls, 0.22 (-0.47-0.96), P overall <.001. IGFBP-1 was increased in HFpEF, 48 (28-79), and HFrEF, 65 (29-101), vs controls, 27(14-35) µg/L, P overall <.001. These patterns persisted after adjusting for metabolic and HF severity confounders. IGF-1 was associated with outcomes in HFrEF, hazard ratio per natural logarithmic increase in IGF-1 SD score 0.51 (95% confidence interval 0.32-0.82, P = .005), but not significantly in HFpEF. IGFBP-1 was not associated with outcomes in either HFpEF nor HFrEF. CONCLUSION: HFpEF and HFrEF phenotypes were similar with regard to increased IGFBP-1 concentrations but differed regarding IGF-1 levels and prognostic role. HFrEF and HFpEF may display different impairment in anabolic drive.

HFpEF and HFrEF exhibit different phenotypes as assessed by leptin and adiponectin.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) exhibits a "reverse metabolic profile". Whether this profile exists in HF with preserved ejection fraction (HFpEF) is unknown. We tested the hypothesis that HFpEF and HFrEF are similar regarding concentrations of and prognostic impact of leptin and adiponectin. METHODS: In patients with HFpEF(n=79), HFrEF(n=84), and controls(n=71), we analyzed serum leptin and adiponectin concentrations, their correlations, and associations with outcome. RESULTS: Leptin levels in HFpEF and HFrEF were increased (p<0.05) compared to controls; with the highest levels in HFpEF, median (IQR), 23.1 (10.2-51.0), vs. HFrEF 15.0 (6.2-33.2), and vs. controls 10.8 (5.4-18.9) ng/mL.There was no difference between HFpEF and HFrEF p=0.125 (adjusted for gender, BMI and age). Leptin was inversely associated with NT-proBNP (r=-0.364 p=0.001) and associated with better outcome in HFrEF (HR per ln increase of leptin 0.76, 95% CI 0.58-0.99, p=0.044) but not in HFpEF. Crude levels of adiponectin were similar in HFpEF: 11.8 (7.9-20.1), HFrEF: 13.7 (7.0-21.1), and controls: 10.5 (7.4-15.1) µg/L. In men, adjusted similarly as leptin, there was no difference between HFpEF and HFrEF, p=0.310 but, compared to controls, higher levels in HFpEF (p=0.044) and HFrEF (p=0.001). Adiponectin correlated positively with NT-proBNP; r=0.396 p<0.001 and higher levels were associated with adverse outcome only in HFrEF (HR per ln increase 2.88 (95% CI 1.02-8.14, p=0.045). CONCLUSION: HFpEF and HFrEF share elevated levels of leptin and adiponectin. However, the concept of reverse metabolic profile could not be confirmed in HFpEF, suggesting that HFpEF might have a conventional metabolic profile, rather than a distinct HF syndrome.