Effect of empagliflozin on cardiac biomarkers in a zebrafish model of heart failure: clues to the EMPA-REG OUTCOME trial?

2017 ◽  
Vol 433 (1-2) ◽  
pp. 97-102 ◽  
Author(s):  
Xingjuan Shi ◽  
Subodh Verma ◽  
Junghwa Yun ◽  
Koroboshka Brand-Arzamendi ◽  
Krishna K. Singh ◽  
...  
Author(s):  
Shivananda B Nayak ◽  
Dharindra Sawh ◽  
Brandon Scott ◽  
Vestra Sears ◽  
Kareshma Seebalack ◽  
...  

Purpose: i) To determine the relationship between the cardiac biomarkers ST2 and NT-proBNP with ejection fraction (EF) in heart failure (HF) patients. ii) Assess whether a superiority existed between the aforementioned cardiac markers in diagnosing the HF with reduced EF. iii) Determine the efficacy of both biomarkers in predicting a 30-day cardiovascular event and rehospitalization in patients with HF with reduced EF iv) To assess the influence of age, gender, BMI, anaemia and renal failure on the ST2 and NT-proBNP levels. Design and Methods: A prospective double-blind study was conducted to obtain data from a sample of 64 cardiology patients. A blood sample was collected to test for ST2 and NT-proBNP. An echocardiogram (to obtain EF value), electrocardiogram and questionnaire were also obtained. Results: Of the 64 patients enrolled, 59.4% of the population had an EF less than 40%. At the end of the 30- day period, 7 patients were warded, 37 were not warded, one died and 17 were non respondent. Both biomarkers were efficacious at diagnosing HF with a reduced EF. However, neither of them were efficacious in predicting 30-day rehospitalization. The mean NT-proBNP values being: not rehospitalized (2114.7486) and 30 day rehospitalization (1008.42860) and the mean ST2 values being: not rehospitalized (336.1975), and 30-day rehospitalization. (281.9657). Conclusion: Neither ST2 or NT-proBNP was efficacious in predicting the short- term prognosis in HF with reduced EF. Both however were successful at confirming the diagnosis of HF in HF patients with reduced EF.


2016 ◽  
Vol 62 (2) ◽  
pp. 360-366 ◽  
Author(s):  
Emily I Schindler ◽  
Jeffrey J Szymanski ◽  
Karl G Hock ◽  
Edward M Geltman ◽  
Mitchell G Scott

Abstract BACKGROUND Galectin-3 (Gal-3) has been suggested as a prognostic biomarker in heart failure (HF) patients that may better reflect disease progression than traditional markers, including B-type natriuretic peptide (BNP) and cardiac troponins. To fully establish the utility of any biomarker in HF, its biologic variability must be characterized. METHODS To assess biologic variability, 59 patients were prospectively recruited, including 23 male and 16 female patients with stable HF and 10 male and 10 female healthy individuals. Gal-3, BNP, and high-sensitivity cardiac troponin I (hs-cTnI) were assayed at 5 time points within a 3-week period to assess short-term biologic variability. Long-term (3-month) biologic variability was assessed with samples collected at enrollment and after 4, 8, and 12 weeks. RESULTS Among healthy individuals, mean short-term biologic variability, expressed as intraindividual CV (CVI), was 4.5% for Gal-3, 29.0% for BNP, and 14.5% for hs-cTnI; long-term biologic variability was 5.5% for Gal-3, 34.7% for BNP, and 14.7% for hs-cTnI. In stable HF patients, mean short-term biologic variability was 7.1% for Gal-3, 22.5% for BNP, and 8.5% for hs-cTnI, and mean long-term biologic variability was 7.7% for Gal-3, 27.6% for BNP, and 9.6% for hs-cTnI. CONCLUSIONS The finding that Gal-3 has minimal intraindividual biological variability adds to its potential as a useful biomarker in HF patients.


2021 ◽  
Vol 4 (5) ◽  
pp. 22389-22402
Author(s):  
Noelia Gonçalves Dos Santos ◽  
Isadora dos Santos Lima ◽  
Lenise Costa De Carvalho ◽  
Diego Cézar Guirra Freitas Andrade ◽  
Mariana de Freitas Rocha ◽  
...  

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
João Pedro Ferreira ◽  
Subodh Verma ◽  
David Fitchett ◽  
Anne Pernille Ofstad ◽  
Sabine Lauer ◽  
...  

Abstract Background Patients with type 2 diabetes (T2D) and metabolic syndrome (MetS) are at greater cardiovascular risk than those with T2D without MetS. In the current report we aim to study the characteristics, cardio-renal outcomes and the effect of empagliflozin in patients with MetS enrolled in the EMPA-REG OUTCOME trial. Methods A total of 7020 patients with T2D and atherosclerotic cardiovascular disease were treated with empagliflozin (10 mg or 25 mg) or placebo for a median of 3.1 years. The World Health Organization MetS criteria could be determined for 6985 (99.5%) patients. We assessed the association between baseline MetS and multiple cardio-renal endpoints using Cox regression models, and we studied the change in the individual component over time of the MetS using mixed effect models. Results MetS at baseline was present in 5740 (82%) patients; these were more often white and had more often albuminuria and heart failure, had lower eGFR and HDL-cholesterol, and higher blood pressure, body mass index, waist circumference, and triglycerides. In the placebo group, patients with MetS had a higher risk of all outcomes including cardiovascular death: HR = 1.73 (95% CI 1.01–2.98), heart failure hospitalization: HR = 2.64 (95% CI 1.22, 5.72), and new or worsening nephropathy: HR = 3.11 (95% CI 2.17–4.46). The beneficial effect of empagliflozin was consistent on all cardio-renal outcomes regardless of presence of MetS. Conclusions A large proportion of the EMPA-REG OUTCOME population fulfills the criteria for MetS. Those with MetS had increased risk of adverse cardio-renal outcomes. Compared with placebo, empagliflozin improved cardio-renal outcomes in patients with and without MetS. Trial registration Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT 01131676


Author(s):  
Sri Lekha Tummalapalli ◽  
Leila R. Zelnick ◽  
Amanda H. Andersen ◽  
Robert H. Christenson ◽  
Christopher R. deFilippi ◽  
...  

Background The Kansas City Cardiomyopathy Questionnaire ( KCCQ ) is a measure of heart failure ( HF ) health status. Worse KCCQ scores are common in patients with chronic kidney disease ( CKD ), even without diagnosed heart failure ( HF ). Elevations in the cardiac biomarkers GDF‐15 (growth differentiation factor‐15), galectin‐3, sST2 (soluble suppression of tumorigenesis‐2), hsTnT (high‐sensitivity troponin T), and NT ‐pro BNP (N‐terminal pro‐B‐type natriuretic peptide) likely reflect subclinical HF in CKD . Whether cardiac biomarkers are associated with low KCCQ scores is not known. Methods and Results We studied participants with CKD without HF in the multicenter prospective CRIC (Chronic Renal Insufficiency Cohort) Study. Outcomes included (1) low KCCQ score <75 at year 1 and (2) incident decline in KCCQ score to <75. We used multivariable logistic regression and Cox regression models to evaluate the associations between baseline cardiac biomarkers and cross‐sectional and longitudinal KCCQ scores. Among 2873 participants, GDF‐15 (adjusted odds ratio 1.42 per SD ; 99% CI , 1.19–1.68) and galectin‐3 (1.28; 1.12–1.48) were significantly associated with KCCQ scores <75, whereas sST2, hsTnT, and NT ‐pro BNP were not significantly associated with KCCQ scores <75 after multivariable adjustment. Of the 2132 participants with KCCQ ≥75 at year 1, GDF‐15 (adjusted hazard ratio, 1.36 per SD ; 99% CI , 1.12–1.65), hsTnT (1.20; 1.01–1.44), and NT ‐pro BNP (1.30; 1.08–1.56) were associated with incident decline in KCCQ to <75 after multivariable adjustment, whereas galectin‐3 and sST2 did not have significant associations with KCCQ decline. Conclusions Among participants with CKD without clinical HF , GDF‐15, galectin‐3, NT ‐pro BNP , and hsTnT were associated with low KCCQ either at baseline or during follow‐up. Our findings show that elevations in cardiac biomarkers reflect early symptomatic changes in HF health status in CKD patients.


2020 ◽  
Vol 9 (4) ◽  
pp. 1130
Author(s):  
Peter Jirak ◽  
Rudin Pistulli ◽  
Michael Lichtenauer ◽  
Bernhard Wernly ◽  
Vera Paar ◽  
...  

Background: Heart failure with preserved ejection fraction (HFpEF) remains an ongoing therapeutic and diagnostic challenge to date. In this study we aimed for an analysis of the diagnostic potential of four novel cardiovascular biomarkers, GDF-15, H-FABP, sST2, and suPAR in HFpEF patients compared to controls as well as ICM, and DCM. Methods: In total, we included 252 stable outpatients and controls (77 DCM, 62 ICM, 18 HFpEF, and 95 controls) in the present study. All patients were in a non-decompensated state and on a stable treatment regimen. Serum samples were obtained and analyzed for GDF-15 (inflammation, remodeling), H-FABP (ischemia and subclinical ischemia), sST2 (inflammation, remodeling) and suPAR (inflammation, remodeling) by means of ELISA. Results: A significant elevation of GDF-15 was found for all heart failure entities compared to controls (p < 0.005). Similarly, H-FABP evidenced a significant elevation in all heart failure entities compared to the control group (p < 0.0001). Levels of sST2 were significantly elevated in ICM and DCM patients compared to the control group and HFpEF patients (p < 0.0001). Regarding suPAR, a significant elevation in ICM and DCM patients compared to the control group (p < 0.0001) and HFpEF patients (p < 0.01) was observed. An AUC analysis identified H-FABP (0.792, 95% CI 0.713–0.870) and GDF-15 (0.787, 95% CI 0.696–0.878) as paramount diagnostic biomarkers for HFpEF patients. Conclusion: Based on their differences in secretion patterns, novel cardiovascular biomarkers might represent a promising diagnostic tool for HFpEF in the future.


2019 ◽  
Vol 8 (2) ◽  
pp. 270 ◽  
Author(s):  
Aneta Aleksova ◽  
Alessia Paldino ◽  
Antonio Beltrami ◽  
Laura Padoan ◽  
Massimo Iacoviello ◽  
...  

Soluble ST2 (sST2) has recently emerged as a promising biomarker in the field of acute cardiovascular diseases. Several clinical studies have demonstrated a significant link between sST2 values and patients’ outcome. Further, it has been found that higher levels of sST2 are associated with an increased risk of adverse left ventricular remodeling. Therefore, sST2 could represent a useful tool that could help the risk stratification and diagnostic and therapeutic work-up of patients admitted to an emergency department. With this review, based on recent literature, we have built sST2-assisted flowcharts applicable to three very common clinical scenarios of the emergency department: Acute heart failure, type 1, and type 2 acute myocardial infarction. In particular, we combined sST2 levels together with clinical and instrumental evaluation in order to offer a practical tool for emergency medicine physicians.


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