#2099 Long term outcomes in chronic kidney disease patients with heart failure with preserved ejection fraction
Authors: Zilisteanu Diana Silvia , Rusu Elena Emanuela , Rosca Monica , Calin Andreea 
Published: May 2024

Abstract

Background and Aims
Heart failure (HF) is frequent in chronic kidney disease (CKD) and leads to high morbidity and mortality in this patient category. The aim of our study is to assess the clinical and biological profile, and outcomes in CKD patients with preserved left ventricular ejection fraction (LVEF).

Method
We prospectively enrolled CKD patients (pts) in pre-dialysis, stratified in two groups by the presence of heart failure symptoms: pts with NYHA class 1-2 (asymptomatic HF) versus pts with NYHA class 3-4 (symptomatic HF). Demographics, clinical history, co-morbidities, physical exam, ambulatory blood pressure monitoring, extensive blood chemistry, systemic inflammation and mineral bone disease parameters were recorded. Cardiac structure and systolic and diastolic function were assessed by echocardiography. Carotid Doppler ultrasound assessed intima media thickness (IMT).
Al patients were followed until death of loss from records; patients with less than 6 months of surveillance were excluded. Primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular mortality, a composite cardiac endpoint composite cardiac endpoint comprising coronary heart disease, heart failure hospitalization and new-onset arrhythmia, and reaching the end stage of renal disease (ESRD).

Results
We included 76 CKD patients (2 pts CKD stage 1, 9 pts CKD stage 2, 19 pts CKD stage 3a, 28 pts CKD stage 3b, 18 pts CKD stage 4) with LVEF ≥ 50%. Mean age 64.7 ± 11.4 years (yrs), men = 56 (73.7%). Mean follow up period was 86 ± 46.4 months (range 6-156 months).
Patients with symptomatic HF (54 pts, 71.1%) were older (68 ± 9 vs 56 ± 12 yrs), hypertensive (98.1% vs 86.4%, p &lt; 0.05), more frequent coronary artery disease (66.7% vs 27.3%, p &lt; 0.05), had worse baseline biological profile: lower eGFR (36.9 ± 12.9 vs 55.5 ± 22.7 ml/min/1.73 m2, p &lt; 0.05), lower serum albumin (4.1 ± 0.5 vs 4.4 ± 0.4 g/dl, p &lt; 0.05), as well as higher levels of osteoprotegerin and fetuin A (p &lt; 0.05). Also, symptomatic HF pts had more severe endothelial disease (higher IMT 0.81 ± 0.14 vs 0.63 ± 0.11 mm, p &lt; 0.05), more severe subclinical LV dysfunction revealed by less negative global longitudinal strain GLS (−16.7 ± 2.66 vs −19.2 ± 2.95, p &lt; 0.05) and higher ratio of mitral velocity to early diastolic velocity of the mitral annulus E/E` (12.64 ± 3.63 vs 9.68 ± 2.73, p &lt; 0.05), as well as higher LV mass index (121.5 ± 31 vs 104.9 ± 22.7 g/m2, p &lt; 0.05) and higher left atrial volume index LAVI (42.8 ± 16.8 vs 31.8 ± 11.3 ml/m2, p &lt; 0.05)
All-cause mortality was 17.1% (13 events), while cardiovascular mortality was 6.6% (5 events). All deaths were recorded in the symptomatic HF group. Also, a higher percent of pts from symptomatic HF group reached the composite cardiac endpoint (44.4% vs 22.7%) and ESRD (33.3% vs 18.2%) compared to asymptomatic HF group.
Kaplan-Meier survival analysis showed significantly higher all-cause mortality (log rang = 0.008) and lower ESRD-free survival (log rank= 0.045) in symptomatic HF group.
All-cause mortality was significantly correlated with NYHA class (p &lt; 0.0001), etiology of CKD (p = 0.038), eGFR (p &lt; 0.0001), proteinuria (p = 0.001), intact PTH (p = 0.008), osteocalcin (p = 0.012), osteopontin (p = 0.029), FGF23 (p = 0.044), IL6 (p = 0.037), GLS (p = 0.023), E/E` (p = 0.009). Cardiovascular mortality was significantly correlated with NYHA class (p = 0.019), etiology of CKD (p = 0.008), eGFR (p = 0.011), proteinuria (p = 0.001), intact PTH (p = 0.008), osteocalcin (p = 0.011), osteopontin (p = 0.006), FGF23 (p = 0.006). Cox regression analysis identified NYHA class (p = 0.004), FGF23 (p = 0.009) and IL6 (p = 0.025) as predictors for all-cause mortality, while E/E` (p = 0.032) and intact PTH (p-0.042) were predictors for cardiovascular mortality.

Conclusion
In our study, CKD pts with symptomatic HF carry a significant burden of morbidity and mortality, even in the case of preserved LV ejection fraction. This emphasizes the need for more comprehensive regular assessments of subclinical cardiac dysfunction in CKD pts. This approach might support targeted interventions, better symptom control, and improved long term outcomes.