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Aim: Fibroblast growth factor 23 (FGF23) is an intensively studied biomarker at the crossroads of cardiovascular disease, heart failure (HF) and chronic kidney disease. Independent associations between increasing FGF23 levels and cardiovascular events were found in many, but not all studies. By analysing data from the TIME-CHF cohort, we sought to investigate the prognostic value of FGF23 in an elderly, multimorbid HF patient cohort. We determined differences between intact (iFGF23) and C-terminal FGF23 (cFGF23) regarding their prognostic value and their levels over time in different HF subgroups according to left ventricular ejection fraction (LVEF).Methods and Results: In this multicentre trial of 622 patients with symptomatic HF aged ≥60 years, we determined iFGF23 and cFGF23 at baseline, 3, 6 and 12-month follow-up. In unadjusted analyses, cFGF23 significantly predicted all HF-related outcomes at all time points. The predictive value of iFGF23 was less and not statistically significant at baseline. After multivariable adjustments, the association between both cFGF23 and iFGF23 and outcome lost statistical significance apart from cFGF23 at month 3. Overall, patients with preserved and mid-range LVEF had higher levels of iFGF23 and cFGF23 than those with reduced LVEF. Levels decreased significantly during the first 3 months in mid-range and reduced LVEF patients, but did not significantly change over time in those with preserved LVEF.Conclusions: Fibroblast growth factor 23 is of limited value regarding risk prediction in this elderly HF population. Potentially heterogeneous roles of FGF23 in different LVEF groups deserve further investigation. [ABSTRACT FROM AUTHOR]

Aims: We sought to compare the generalizability and prognostic implications of heart failure with preserved ejection fraction (HFpEF) scores (HFA‐PEFF and H2FPEF score) in Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) and Phosphodiesterase‐5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial participants and matched controls from the Atherosclerosis Risk in Community (ARIC) study. Methods and results: Based on the respective scores, the study participants from the TOPCAT (N = 356), RELAX (N = 216), and ARIC (N = 379) studies were categorized as having a low, intermediate, or high likelihood of HFpEF. Age, sex, and race matched controls free of cardiovascular disease who had unexplained dyspnoea were used to evaluate the diagnostic performance. The prognostic value of scores was assessed using multivariable‐adjusted Cox regression analyses. The median HFA‐PEFF scores in the TOPCAT, RELAX, and ARIC studies were 5.0 [interquartile range (IQR): 5.0–6.0], 4.0 (IQR: 2.0–4.0), and 3.0 (IQR: 2.0–4.0), respectively. The median H2FPEF scores in the three studies were 5.5 (IQR: 4.0–7.0), 6.0 (IQR: 4.0–7.0), and 3.0 (IQR: 2.0–5.0), respectively. A low HFA‐PEFF and H2FPEF score can rule out HFpEF with high sensitivity (99.5% and 99.6%, respectively) and negative predictive value (95.7% and 98.3%, respectively). A high HFA‐PEFF and H2FPEF score can rule‐in HFpEF with good specificity (82.8% and 95.6%, respectively) and positive predictive value (79.9% and 90.4%, respectively). Among TOPCAT participants, the hazard for adverse cardiovascular events per point increase in HFA‐PEFF and H2FPEF score was 1.26 (95% confidence interval: 0.98–1.63) and 1.01 (95% confidence interval: 0.88–1.15), respectively. A higher H2FPEF score was associated with lower peak oxygen intake in RELAX trial participants (adjusted P = 0.01). Conclusions: The HFA‐PEFF and the H2FPEF scores are reliable diagnostic tools for HFpEF. The prognostic utility of HFpEF scores requires further validation in larger rigorously phenotyped populations. [ABSTRACT FROM AUTHOR]

Aims: Whether and how iron deficiency (ID) impacts patients with heart failure (HF) with preserved ejection fraction (HFpEF) remain unclear. The aim of our study was to investigate the impact of ID on functional status, exercise capacity, and prognosis in HFpEF. Methods and results: The study population consisted of 300 HFpEF patients. ID was defined as serum ferritin <100 μg/L or 100–300 μg/L and transferrin‐saturation <20%. Baseline functional status, quality of life (HADS score and EQ 5D index), 6 min walking test, echocardiography, and outcome (all‐cause mortality and combined all cause‐mortality and HF hospitalization) were evaluated. ID was found in 159 (53%) patients. Patients with ID had a worse prognosis with a higher combined endpoint of all‐cause mortality and HF hospitalization after 4 years of follow‐up (log rank = 0.008). Pulmonary hypertension, depression, and thyroid disease were more prevalent in the ID group. Multivariable analysis showed that ID was independently associated with body mass index (P = 0.003), pulmonary hypertension (P = 0.008), and thyroid disease (P = 0.01). Although patients with ID had a lower exercise capacity compared with patients without ID (393 m [294–455] vs. 344 m [260–441], P = 0.008), there was no significant correlation after multivariable correction for age, BMI, NT‐proBNP, DM, and depression. Conclusions: Heart failure with preserved ejection fraction patients with ID have a worse prognosis and impaired exercise capacity compared with those without ID. However, although a trend was observed, after multivariable correction ID was no longer significantly associated with a reduced exercise capacity. This reflects that impaired exercise capacity in HFpEF is complex and seems multifactorial. Interestingly, pulmonary hypertension was an independent predictor of both ID and exercise capacity. [ABSTRACT FROM AUTHOR]

Background: The relationship between longitudinal clinical congestion pattern and heart failure outcome is uncertain. This study was designed to assess the prevalence of congestion over time and to investigate its impact on outcome in chronic heart failure.Methods: A total of 588 patients with chronic heart failure older than 60 years of age with New York Heart Association (NYHA) functional class ≥II from the TIME-CHF study were included. The endpoints for this study were survival and hospitalization-free heart failure survival. Orthopnea, NYHA ≥III, paroxysmal nocturnal dyspnea, hepatomegaly, peripheral pitting edema, jugular venous distension, and rales were repeatedly investigated and related to outcomes. These congestion-related signs and symptoms were used to design a 7-item Clinical Congestion Index.Results: Sixty-one percent of patients had a Clinical Congestion Index ≥3 at baseline, which decreased to 18% at month 18. During the median [interquartile range] follow-up of 27.2 [14.3-39.8] months, 17%, 27%, and 47% of patients with baseline Clinical Congestion Index of 0, 1-2, and ≥3 at inclusion, respectively, died (P <.001). Clinical Congestion Index was identified as an independent predictor of mortality at all visits (P <.05) except month 6 and reduced hospitalization-free heart failure survival (P <.05). Successful decongestion was related to better outcome as compared to persistent congestion or partial decongestion (log-rank P <0.001).Conclusions: The extent of congestion as assessed by means of clinical signs and symptoms decreased over time with intensified treatment, but it remained present or relapsed in a substantial number of patients with heart failure and was associated with poor outcome. This highlights the importance of appropriate decongestion in chronic heart failure. [ABSTRACT FROM AUTHOR]

Patients with an assigned H SB 2 sb FPEF category higher than their assigned HFA-PEFF category (H SB 2 sb FPEF > HFA-PEFF) most often suffered from AF (82.0% vs. 14.0% and 61%, I P i < 0.001) and had the highest BMI (33.5 ± 6.5 vs. 27.9 ± 4.9 and 31.0 ± 6.1, I P i < 0.001). The HFA-PEFF and H2FPEF scores largely disagree in classifying patients with suspected heart failure with preserved ejection fraction The H SB 2 sb FPEF and HFA-PEFF scores have recently been proposed to solve the clinical dilemma of diagnosing heart failure with preserved ejection fraction (HFpEF).1,2 The H SB 2 sb FPEF score includes four clinical [age, body mass index (BMI), atrial fibrillation (AF) and hypertension] and two echocardiographic items (E/e' and right ventricular pressure). [Extracted from the article]