Dapagliflozin Improved Cardiac Function and Structure in Diabetic Patients with Preserved Ejection Fraction: Results of a Single Centre, Observational Prospective Study.

Sodium-glucose cotransporter inhibitors (SGLT2i) have demonstrated a reduction in cardiovascular events in diabetes and heart failure (HF). The mechanisms underlying this benefit are not well known and data are contradictory. The purpose of this study is to analyse the effect of dapagliflozin on cardiac structure and function in patients with normal ejection fraction. Between October 2020 and October 2021, we consecutively included 31 diabetic patients without prior history of SGLT2i use. In all of them, dapagliflozin treatment was started. At inclusion and during six months of follow-up, different clinical, ECG, analytical, and echocardiographic (standard, 3D, and speckle tracking) variables were recorded. After a follow-up period of 6.6 months, an average reduction of 18 g (p = 0.028) in 3D-estimated left ventricle mass was observed. An increase in absolute left ventricle global longitudinal strain (LV-GLS) of 0.3 (p = 0.036) was observed, as well as an increase in isovolumetric relaxation time (IVRT) of 10.5 ms (p = 0.05). Moreover, dapagliflozin decreased the levels of plasma creatin-kinase (CK-MB) and atrial natriuretic peptide (ANP). In conclusion, our data show that the use of SGLT2i is associated with both structural (myocardial mass) and functional (IVRT, LV-GLS) cardiac improvements in a population of diabetic patients with normal ejection fraction.

The role of bioimpedance analysis in overweight and obese patients with acute heart failure: a pilot study.

AIMS: Residual congestion at the time of hospital discharge is an important readmission risk factor, and its detection with physical examination and usual diagnostic techniques have strong limitations in overweight and obese patients. New tools like bioelectrical impedance analysis (BIA) could help to determine when euvolaemia is reached. The aim of this study was to investigate the usefulness of BIA in management of heart failure (HF) in overweight and obese patients. METHODS AND RESULTS: Our study is a single-centre, single-blind, randomized controlled trial that included 48 overweight and obese patients admitted for acute HF. The study population was randomized into two arms: BIA-guided group and standard care. Serum electrolytes, kidney function, and natriuretic peptides were followed up during their hospital stay and at 90 days after discharge. The primary endpoint was development of severe acute kidney injury (AKI) defined as an increase in serum creatinine by >0.5 mg/dL during hospitalization, and the main secondary endpoint was the reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels during hospitalization and within 90 days after discharge. The BIA-guided group showed a remarkable lower incidence of severe AKI, although no significant differences were found (41.4% vs. 16.7%; P = 0.057). The proportion of patients who achieved levels of NT-proBNP < 1000 pg/mL at 90 days was significantly higher in the BIA-guided group than in the standard group (58.8% vs. 25%; P = 0.049). No differences were observed in the incidence of adverse outcomes at 90 days. CONCLUSIONS: Among overweight and obese patients with HF, BIA reduces NT-proBNP levels at 90 days compared with standard care. In addition, there is a trend towards lower incidence of AKI in the BIA-guided group. Although more studies are required, BIA could be a useful tool in decompensated HF management in overweight and obese patients.

Plasma Levels of Monocyte Chemoattractant Protein-1, n-Terminal Fragment of Brain Natriuretic Peptide and Calcidiol Are Independently Associated with the Complexity of Coronary Artery Disease.

BACKGROUND AND OBJECTIVES: We investigated the relationship of the Syntax Score (SS) and coronary artery calcification (CAC), with plasma levels of biomarkers related to cardiovascular damage and mineral metabolism, as there is sparse information in this field. METHODS: We studied 270 patients with coronary disease that had an acute coronary syndrome (ACS) six months before. Calcidiol, fibroblast growth factor-23, parathormone, phosphate and monocyte chemoattractant protein-1 [MCP-1], high-sensitivity C-reactive protein, galectin-3, and N-terminal pro-brain natriuretic peptide [NT-proBNP] levels, among other biomarkers, were determined. CAC was assessed by coronary angiogram as low-grade (0-1) and high-grade (2-3) calcification, measured with a semiquantitative scale ranging from 0 (none) to 3 (severe). For the SS study patients were divided in SS<14 and SS≥14. Multivariate linear and logistic regression analyses were performed. RESULTS: MCP-1 predicted independently the SS (RC = 1.73 [95%CI = 0.08-3.39]; p = 0.040), along with NT-proBNP (RC = 0.17 [95%CI = 0.05-0.28]; p = 0.004), male sex (RC = 4.15 [95%CI = 1.47-6.83]; p = 0.003), age (RC = 0.13 [95%CI = 0.02-0.24]; p = 0.020), hypertension (RC = 3.64, [95%CI = 0.77-6.50]; p = 0.013), hyperlipidemia (RC = 2.78, [95%CI = 0.28-5.29]; p = 0.030), and statins (RC = 6.12 [95%CI = 1.28-10.96]; p = 0.013). Low calcidiol predicted high-grade calcification independently (OR = 0.57 [95% CI = 0.36-0.90]; p = 0.013) along with ST-elevation myocardial infarction (OR = 0.38 [95%CI = 0.19-0.78]; p = 0.006), diabetes (OR = 2.35 [95%CI = 1.11-4.98]; p = 0.028) and age (OR = 1.37 [95%CI = 1.18-1.59]; p<0.001). During follow-up (1.79 [0.94-2.86] years), 27 patients developed ACS, stroke, or transient ischemic attack. A combined score using SS and CAC predicted independently the development of the outcome. CONCLUSIONS: MCP-1 and NT-proBNP are independent predictors of SS, while low calcidiol plasma levels are associated with CAC. More studies are needed to confirm these data.

Important abnormalities of bone mineral metabolism are present in patients with coronary artery disease with a mild decrease of the estimated glomerular filtration rate.

Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is characterized by increased circulating levels of parathormone (PTH) and fibroblast growth factor 23 (FGF23), bone disease, and vascular calcification, and is associated with adverse outcomes. We studied the prevalence of mineral metabolism disorders, and the potential relationship between decreased estimated glomerular filtration rate (eGFR) and CKD-MBD in coronary artery disease patients in a cross-sectional study of 704 outpatients 7.5 ± 3.0 months after an acute coronary syndrome. The mean eGFR (CKD Epidemiology Collaboration formula) was 75.8 ± 19.1 ml/min/1.73 m(2). Our patients showed lower calcidiol plasma levels than a healthy cohort from the same geographical area. In the case of men, this finding was present despite similar creatinine levels in both groups and older age of the healthy subjects. Most patients (75.6 %) had an eGFR below 90 ml/min/1.73 m(2) (eGFR categories G2-G5), with 55.3 % of patients exhibiting values of 60-89 ml/min/1.73 m(2) (G2). PTH (r = -0.3329, p < 0.0001) and FGF23 (r = -0.3641, p < 0.0001) levels inversely correlated with eGFR, whereas calcidiol levels and serum phosphate levels did not. Overall, PTH levels were above normal in 34.9 % of patients. This proportion increased from 19.4 % in G1 category patients, to 33.7 % in G2 category patients and 56.6 % in G3-G5 category patients (p < 0.001). In multivariate analysis, eGFR and calcidiol levels were the main independent determinants of serum PTH. The mean FGF23 levels were 69.9 (54.6-96.2) relative units (RU)/ml, and 33.2 % of patients had FGF23 levels above 85.5 RU/ml (18.4 % in G1 category patients, 30.0 % in G2 category patients, and 59.2 % in G3-G5 category patients; p < 0.001). In multivariate analysis, eGFR was the main predictor of FGF23 levels. Increased phosphate levels were present in 0.7 % of the whole sample: 0 % in G1 category patients, 0.3 % in G2 category patients, and 2.8 % in G3-G5 category patients (p = 0.011). Almost 90 % of patients had calcidiol insufficiency without significant differences among the different degrees of eGFR. In conclusion, in patients with coronary artery disease there is a large prevalence of increased FGF23 and PTH levels. These findings have an independent relationship with decreased eGFR, and are evident at an eGFR of 60-89 ml/min/1.73 m(2). Then, mild decreases in eGFR must be taken in consideration by the clinician because they are associated with progressive abnormalities of mineral metabolism.

Differential profile in inflammatory and mineral metabolism biomarkers in patients with ischemic heart disease without classical coronary risk factors.

BACKGROUND: Patients with coronary heart disease (CHD) without classical cardiovascular risk factors (CRFs) are uncommon, and their profile has not been thoroughly studied. In CHD patients, we have assessed the differences in several biomarkers between those with and without CRF. METHODS: We studied 704 patients with CHD, analyzing plasma levels of biomarkers related to inflammation, thrombosis, renal damage, and heart failure: high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), galectin-3, N-terminal fragment of brain natriuretic peptide (NT-pro-BNP), calcidiol (vitamin D metabolite), fibroblast growth factor-23 (FGF-23), parathormone, and phosphate. RESULTS: Twenty patients (2.8%) exhibited no CRFs. Clinical variables were well balanced in both groups, with the logical exceptions of no use of antidiabetic drugs, lower triglyceride and glucose, and higher high-density lipoprotein cholesterol in no-CRF patients. No-CRF patients showed lower hs-CRP (2.574±3.120 vs. 4.554±9.786mg/L; p=0.018), MCP-1 (114.75±36.29 vs. 143.56±65.37pg/ml; p=0.003), and FGF-23 (79.28±40.22 vs. 105.17±156.61RU/ml; p=0.024), and higher calcidiol (23.66±9.12 vs. 19.49±8.18ng/ml; p=0.025) levels. At follow-up, 10.0% vs. 11.0% patients experienced acute ischemic event, heart failure, or death in the non-CRF and CRF groups, respectively (p=0.815, log-rank test). The limited number of non-CRF patients may have influenced this finding. A Cox regression analysis in the whole population showed that high calcidiol, and low MCP-1 and FGF-23 plasma levels are associated with a better prognosis. CONCLUSIONS: CHD patients without CRFs show a favorable biomarker profile in terms of inflammation and mineral metabolism. Further studies are needed to investigate whether this difference translates into a better prognosis.

Coexistence of low vitamin D and high fibroblast growth factor-23 plasma levels predicts an adverse outcome in patients with coronary artery disease.

OBJECTIVE: Vitamin D and fibroblast growth factor-23 (FGF-23) are related with cardiovascular disorders. We have investigated the relationship of calcidiol (vitamin D metabolite) and FGF-23 plasma levels with the incidence of adverse outcomes in patients with coronary artery disease. METHODS: Prospective follow-up study of 704 outpatients, attending the departments of Cardiology of four hospitals in Spain, 6-12 months after an acute coronary event. Baseline calcidiol, FGF-23, parathormone, and phosphate plasma levels were assessed. The outcome was the development of acute ischemic events (any acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Cox regression adjusted for the main confounders was performed. RESULTS: Calcidiol levels showed a moderate-severe decrease in 57.3% of cases. Parathormone, FGF-23, and phosphate levels were increased in 30.0%, 11.5% and 0.9% of patients, respectively. Only 22.4% of patients had glomerular filtration rate<60 ml/min1.73 m2. After a mean follow-up was 2.15±0.99 years, 77 patients developed the outcome. Calcidiol (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.48-0.94; p = 0.021) and FGF-23 (HR = 1.13; 95% CI = 1.04-1.23; p = 0.005) plasma levels predicted independently the outcome. There was a significant interaction between calcidiol and FGF-23 levels (p = 0.025). When the population was divided according to FGF-23 levels, calcidiol still predicted the outcome independently in patients with FGF-23 levels higher than the median (HR = 0.50; 95% CI = 0.31-0.80; p = 0.003) but not in those with FGF-23 levels below this value (HR = 1.03; 95% CI = 0.62-1.71; p = 0.904). CONCLUSIONS: Abnormalities in mineral metabolism are frequent in patients with stable coronary artery disease. In this population, low calcidiol plasma levels predict an adverse prognosis in the presence of high FGF-23 levels.

Ergonovine provocative test in Caucasian patients with left ventricular apical ballooning syndrome.

Of a series of 346 consecutive patients with chest pain and no significant coronary stenosis studied with ergonovine provocative test (EPT), 18 fulfilled diagnostic criteria for left ventricular apical ballooning syndrome (LVABS). EPT was negative in all these patients. On the other 328 patients, EPT was positive in 69 (21%). LVABS patients were more frequently women (94 vs. 30%), had a lower left ventricular ejection fraction (0.41 ± 0.11 vs. 0.55 ± 0.09), more troponin T level increments (83 vs. 23%), and a higher prevalence of stress situations (72 vs. 3%) than patients EPT positive.