Background: Electrocardiographic features are well-known for heart failure with reduced ejection fraction (HFrEF), but not for left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF). As ECG features could help to identify high-risk individuals in primary care, we systematically reviewed the literature for ECG features diagnosing women and men suspected of LVDD and HFpEF.Methods and Results: Among the 7,127 records identified, only 10 studies reported diagnostic measures, of which 9 studied LVDD. For LVDD, the most promising features were T-end-P/(PQ*age), which is the electrocardiographic equivalent of the passive-to-active filling (AUC: 0.91–0.96), and repolarization times (QTc interval ≥ 350 ms, AUC: 0.85). For HFpEF, the Cornell product ≥ 1,800 mm*ms showed poor sensitivity of 40% (AUC: 0.62). No studies presented results stratified by sex.Conclusion: Electrocardiographic features are not widely evaluated in diagnostic studies for LVDD and HFpEF. Only for LVDD, two ECG features related to the diastolic interval, and repolarization measures showed diagnostic potential. To improve diagnosis and care for women and men suspected of heart failure, reporting of sex-specific data on ECG features is encouraged.

Aims The HFA‐PEFF score was developed to optimize diagnosis and to aid in early recognition of heart failure (HF) with preserved ejection fraction (HFpEF) in patients who present with HF‐like symptoms. Recognizing early‐HFpEF phenogroups is essential to better understand progression towards overt HFpEF and pave the way for early intervention and treatment. Whether the HFA‐PEFF domain scores can identify ‘early‐HFpEF’ phenogroups remains unknown. The aims of this pilot study are to (i) identify distinct phenogroups by cluster analysis of HFA‐PEFF domain scores in subjects that present with HF‐like symptoms and (ii) study whether these phenogroups may be associated with distinct blood proteome profiles. Methods and results Subjects referred to the Cardiology Centers of the Netherlands, location Utrecht, with non‐acute possibly cardiac‐related symptoms (such as dyspnoea or fatigue) were prospectively enrolled in the HELPFul cohort (N = 507) and were included in the current analysis. Inclusion criteria for this study were (i) age ≥ 45 years and (ii) a left ventricular ejection fraction (LVEF) ≥ 50%, in the absence of a history of HF, coronary artery disease, congenital heart disease, or any previous cardiac interventions. Multinominal‐based clustering with latent class model using the HFA‐PEFF domain scores (functional, structural, and biomarker scores) as input was used to detect distinct phenotypic clusters. For each bootstrapping run, the 92 Olink proteins were analysed for their association with the identified phenogroups. Four distinct phenogroups were identified in the current analysis (validated by bootstrapping 1000×): (i) no left ventricular diastolic dysfunction (no LVDD, N = 102); (ii) LVDD with functional left ventricular (LV) abnormalities (N = 204); (iii) LVDD with functional and structural LV abnormalities (N = 204); and (iv) LVDD with functional and structural LV abnormalities and elevated BNP (N = 107). The HFA‐PEFF total score risk categories significantly differed between the phenogroups (P < 0.001), with an increase of the HFA‐PEFF score from Phenogroup 1 to 4 (low/intermediate/high HFA‐PEFF risk score: Phenogroup 1: 88%/12%/0%; Phenogroup 2: 9%/91%/0%; Phenogroup 3: 0%/92%/8%; Phenogroup 4: 5%/83%/12%). Thirty‐two out of the 92 Olink protein biomarkers significantly differed among the phenogroups. The top eight biomarkers—N‐terminal prohormone brain natriuretic peptide, growth differentiation factor‐15, matrix metalloproteinase‐2, osteoprotegerin, tissue inhibitor of metalloproteinase‐4, chitinase‐3‐like protein 1, insulin‐like growth factor‐binding protein 2, and insulin‐like growth factor‐binding protein 7—are mainly involved in inflammation and extracellular matrix remodelling, which are currently proposed key processes in HFpEF pathophysiology. Conclusions This study identified distinct phenogroups by using the HFA‐PEFF domain scores in ambulant subjects referred for HF‐like symptoms. The newly identified phenogroups accompanied by their circulating biomarkers profile might aid in a ...

Background and Aims Impaired kidney function increase the risk of cardiovascular disease. However, it remains unclear whether this crosstalk between organs already exists at early stages in the disease trajectory and whether this risk varies with age and other factors. We aim to investigate the association between renal dysfunction and early structural and functional cardiac abnormalities in a cohort of participants referred to a cardiology outpatient department. Method We included participants from HELPFul (i.e. HEart failure with Preserved ejection Fraction in patients at risk for cardiovascular disease), a case-cohort study at Dutch cardiology outpatient clinics, who were aged 45 years and older without history of cardiovascular disease. A random sample of participants enriched with cases (defined as an early filling (E) to early diastolic mitral annular velocity (e’) (E/e’) ratio of ≥8 measured with echocardiography) was included in our study. Routine care measurements, including echocardiography and laboratory testing at the outpatient clinic were collected for all participants. An expert panel decided on presence or absence of heart failure with preserved ejection fraction (HFpEF), and left ventricular diastolic dysfunction (LVDD), guided by available international guidelines. The association between renal function, in terms of estimated glomerular filtration rate (eGFR) categories, and diagnosis of HFpEF and LVDD was assessed with multivariable logistic regression analyses, adjusted for cardiovascular and lifestyle risk factors. The association between renal function, in terms of creatinine and cystatin C levels, and echocardiographic parameters, including E/e’ ratio, LAVI (Left atrial volume index), LVMI (left ventricular mass index), and E/A (early (E) to late (A) ventricular filling ratio, was assessed with multivariable linear regression analyses, adjusted for age, sex, cardiovascular and lifestyle risk factors. Adjusted odds ratios (OR) were reported and the corresponding 95% confidence interval (95%CI). Results 777 participants were included, mean age 62.9 (SD: 9.3) years, 67.3% were female. Hundred and fifty-six (20.1%) participants had mild renal dysfunction (eGFR: 60-89 ml/min/1.73 m2), and 24 (3.1%) moderate renal dysfunction (eGFR: 30-59 ml/min/1.73 m2). HFpEF and LVDD was more common in participants with moderate renal dysfunction (13% and 33%, respectively) than in those with normal renal function (6% and 16%, respectively). In the multivariable regression model. participants with both mild and moderate renal dysfunction had a higher likelihood of being diagnosed with HFpEF (OR: 2.82, 95%CI: 1.32 to 5.91; and OR: 5.37, 95%CI: 1.11 to 19.88, respectively), LVDD (OR: 2.08, 95%CI: 1.28 to 3.36; and OR: 2.92, 95%CI: 1.04 to 7.55, respectively), compared with participants with a normal renal function. However, no significant association between creatinine or cystatin C with E/e’, LAVI, LVMI, and E/A ratio was found after adjustment for age, sex, and cardiovascular risk and lifestyle factors. Conclusion Mild renal dysfunction is related to both LVDD and HFpEF, however, this might be partly explained by a higher age in patients with renal dysfunction. Further studies are warranted to determine if preventive cardiac treatment in patients with early renal dysfunction will benefit clinical outcomes.