Soluble ST2 Is a Sensitive and Specific Biomarker for Fulminant Myocarditis.

Background The aim of the study was to identify biomarkers that can facilitate early diagnosis and treatment of fulminant myocarditis (FM) in order to reduce mortality. Methods and Results First, the expression profiles of circulating cytokines were determined in the plasma samples from 4 patients with FM and 4 controls using human cytokine arrays. The results showed that 39 cytokines from patients with FM were changed at admission. Among them, 8 cytokines returned to normal levels at discharge, including soluble ST2 (sST2), which showed the most marked dynamic changes from disease onset to resolution. Then, in a cohort of 76 patients with FM, 57 patients with acute hemodynamic dysfunction attributable to other causes, and 56 patients with non-FM, receiver operating characteristic curve analyses suggested that plasma sST2 level was able to differentiate FM from non-FM or other FM-unrelated acute heart failure more robustly N-terminal pro-B-type natriuretic peptide or cardiac troponin I. Moreover, longitudinal analysis of plasma sST2 was performed in 10 patients with FM during hospitalization and 16 patients with FM during follow-up. Finally, the diagnostic value was validated in an additional 26 patients with acute onset of unstable hemodynamics. The cutoff value of plasma sST2 for optimal diagnosis of FM was established at 58.39 ng/mL, where a sensitivity of 85.7% and specificity of 94.7% were achieved. Conclusions Elevated sST2 level was associated with mechanical stress or inflammation. Especially, sST2 might be used as a potential biomarker for the rapid diagnosis of FM, which was characterized by strong mechanical stretch stimulation and severe inflammatory response. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03268642.

Decongestion, kidney injury and prognosis in patients with acute heart failure.

BACKGROUND: In patients with acute heart failure (AHF), the development of worsening renal function with appropriate decongestion is thought to be a benign functional change and not associated with poor prognosis. We investigated whether the benefit of decongestion outweighs the risk of concurrent kidney tubular damage and leads to better outcomes. METHODS: We retrospectively analyzed data from the AKINESIS study, which enrolled AHF patients requiring intravenous diuretic therapy. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and B-type natriuretic peptide (BNP) were serially measured during the hospitalization. Decongestion was defined as ≥30% BNP decrease at discharge compared to admission. Univariable and multivariable Cox models were assessed for one-year mortality. RESULTS: Among 736 patients, 53% had ≥30% BNP decrease at discharge. Levels of uNGAL and BNP at each collection time point had positive but weak correlations (r ≤ 0.133). Patients without decongestion and with higher discharge uNGAL values had worse one-year mortality, while those with decongestion had better outcomes regardless of uNGAL values (p for interaction 0.018). This interaction was also significant when the change in BNP was analyzed as a continuous variable (p < 0.001). Although higher peak and discharge uNGAL were associated with mortality in univariable analysis, only ≥30% BNP decrease was a significant predictor after multivariable adjustment. CONCLUSIONS: Among AHF patients treated with diuretic therapy, decongestion was generally not associated with kidney tubular damage assessed by uNGAL. Kidney tubular damage with adequate decongestion does not impact outcomes; however, kidney injury without adequate decongestion is associated with a worse prognosis.

THE ROLE OF NT-PROBNP AND ST2 BIOMARKERS IN PATIENTS WITH ACUTE CORONARY SYNDROME.

OBJECTIVE: The aim: To determine the diagnostic value of serum levels of ST2 in patients with the acute coronary syndrome (ACS) and its correlation with NT-proBNP levels. PATIENTS AND METHODS: Materials and methods: NT-proBNP and ST2 concentration in serum of patients was measured on admission to the hospital and on the 10th day of the treatment using NT-proBNP ELISA (Biomedica, Slovakia) and Presage ST2 assay (Critical Diagnostics, USA), respectively. RESULTS: Results: Statistically significant direct correlations (p<0.05). The simultaneous increase of ST2 and NT-proBNP serum levels above their threshold in patients with ACSelST (sensitivity - 92.5 %, specificity - 74.2 %, AUC - 0.893, р<0.05) indicated a significant risk of cardiovascular (CV) complications of acute myocardial infarction (AMI) during the inpatient period, e.g. acute heart failure, acute LV aneurysm, recurrent AMI, as well as rhythm and conductivity disturbances. CONCLUSION: Conclusions: The data suggest that both ST2 and NT-proBNP may prove useful in predicting unfavorable prognosis during the inpatient care of AMI, as the simultaneous increase of these biomarkers above their threshold values indicates a significant risk of CV complications.

Relation of Decongestion and Time to Diuretics to Biomarker Changes and Outcomes in Acute Heart Failure.

Prompt treatment may mitigate the adverse effects of congestion in the early phase of heart failure (HF) hospitalization, which may lead to improved outcomes. We analyzed 814 acute HF patients for the relationships between time to first intravenous loop diuretics, changes in biomarkers of congestion and multiorgan dysfunction, and 1-year composite end point of death or HF hospitalization. B-type natriuretic peptide (BNP), high sensitivity cardiac troponin I (hscTnI), urine and serum neutrophil gelatinase-associated lipocalin, and galectin 3 were measured at hospital admission, hospital day 1, 2, 3 and discharge. Time to diuretics was not correlated with the timing of decongestion defined as BNP decrease ≥ 30% compared with admission. Earlier BNP decreases but not time to diuretics were associated with earlier and greater decreases in hscTnI and urine neutrophil gelatinase-associated lipocalin, and lower incidence of the composite end point. After adjustment for confounders, only no BNP decrease at discharge was significantly associated with mortality but not the composite end point (p = 0.006 and p = 0.062, respectively). In conclusion, earlier time to decongestion but not the time to diuretics was associated with better biomarker trajectories. Residual congestion at discharge rather than the timing of decongestion predicted a worse prognosis.

Potential Utility of Cardiorenal Biomarkers for Prediction and Prognostication of Worsening Renal Function in Acute Heart Failure.

BACKGROUND: Multiple different pathophysiologic processes can contribute to worsening renal function (WRF) in acute heart failure. METHODS AND RESULTS: We retrospectively analyzed 787 patients with acute heart failure for the relationship between changes in serum creatinine and biomarkers including brain natriuretic peptide, high sensitivity cardiac troponin I, galectin 3, serum neutrophil gelatinase-associated lipocalin, and urine neutrophil gelatinase-associated lipocalin. WRF was defined as an increase of greater than or equal to 0.3 mg/dL or 50% in creatinine within first 5 days of hospitalization. WRF was observed in 25% of patients. Changes in biomarkers and creatinine were poorly correlated (r ≤ 0.21) and no biomarker predicted WRF better than creatinine. In the multivariable Cox analysis, brain natriuretic peptide and high sensitivity cardiac troponin I, but not WRF, were significantly associated with the 1-year composite of death or heart failure hospitalization. WRF with an increasing urine neutrophil gelatinase-associated lipocalin predicted an increased risk of heart failure hospitalization. CONCLUSIONS: Biomarkers were not able to predict WRF better than creatinine. The 1-year outcomes were associated with biomarkers of cardiac stress and injury but not with WRF, whereas a kidney injury biomarker may prognosticate WRF for heart failure hospitalization.

Management of Dyslipidemia in Individuals with Low-to-Moderate Cardiovascular Risk: Role of Nutraceuticals.

Cardiovascular diseases (CVDs) are the leading cause of premature deaths globally and in Ukraine. Dyslipidemia is a recognized risk factor for the development of CVD. Therefore, early detection and appropriate management of dyslipidemia are essential for the primary prevention of CVDs. However, currently, there is a lack of Ukraine-specific guideline recommendations focusing on the management of dyslipidemia in individuals with low-to-moderate CV risk, thus creating an urgent need for structured and easily implementable clinical recommendations/guidelines specific to the country. An expert panel of cardiologists, endocrinologists, and family physicians convened in Ukraine in March 2019. The expert panel critically reviewed and analyzed the current literature and put forth the following recommendations for the management of dyslipidemia in individuals with low-to-moderate risk of CVDs specific to Ukraine: (1) family physicians have the greatest opportunities in carrying out primary prevention; (2) lipid-lowering interventions are essential for primary prevention as per guidelines; (3) a number of nutraceuticals and nutraceutical combinations with clinically established lipid-lowering properties can be considered for primary prevention; they also have a suggested role as an alternative therapy for statin-intolerant patients; (4) on the basis of clinical evidence, nutraceuticals are suggested by guidelines for primary prevention; (5) red yeast rice has potent CV-risk-lowering potential, in addition to lipid-lowering properties; (6) in patients with low-to-moderate cardiovascular risk, a nutraceutical combination of low-dose red yeast rice and synergic lipid-lowering compounds can be used as integral part of guideline-recommended lifestyle interventions for effective primary prevention strategy; (7) nutraceutical combination can be used in patients aged 18 to 75+ years; its use is particularly appropriate in the age group of 18-44 years; (8) it is necessary to attract the media (websites, etc.) to increase patient awareness on the importance of primary prevention; and (9) it is necessary to legally separate nutraceuticals from dietary supplements. These consensus recommendations will help physicians in Ukraine effectively manage dyslipidemia in individuals with low-to-moderate CV risk.

Is Arterial Stiffness a Determinant of Hypotension?

INTRODUCTION: Previous observation identified both hypotension and arterial aging, indexed as Pulse Wave Velocity (PWV), as significant determinants of cognitive decline in older subjects. AIM: To investigate the role of PWV as a determinant of hypotension in older patients. METHODS: A cohort of 344 subjects came to our Outpatient Clinic, free of cancer, acute myocardial infarction or stroke, atrial fibrillation, renal, hepatic or cardiac failure, secondary hypertension, or thyroid disease. RESULTS: Hypotension occurred in 49% of participants. SBP levels (OR 0.79, 95% CI 0.67-0.84, p < 0.01), PWV (OR 0.86, 95% CI 0.77-0.94, p < 0.01), and use of beta-blockers (OR 2.42, 95% CI 1.09-5.36, p < 0.05), were independent determinants of the risk of hypotension. CONCLUSIONS: Hypotension is a quite common phenomenon in older subjects. Its prevention requires a more accurate management of hypertension aimed at better identifying which older subjects in whom intensive BP control may be harmful and those who may benefit from it.

Short-term prognostic implications of serum and urine neutrophil gelatinase-associated lipocalin in acute heart failure: findings from the AKINESIS study.

AIMS: Kidney impairment has been associated with worse outcomes in acute heart failure (AHF), although recent studies challenge this association. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker of kidney tubular injury. Its prognostic role in AHF has not been evaluated in large cohorts. The present study aimed to determine if serum NGAL (sNGAL) or urine NGAL (uNGAL) is superior to creatinine for predicting short-term outcomes in AHF. METHODS AND RESULTS: The study was conducted in an international, multicentre, prospective cohort consisting of 927 patients with AHF. Admission and peak values of sNGAL, uNGAL and uNGAL/urine creatinine (uCr) ratio were compared to admission and peak serum creatinine (sCr). The composite endpoints were death, initiation of renal replacement therapy, heart failure (HF) readmission and any emergent HF-related outpatient visit within 30 and 60 days, respectively. The mean age of the cohort was 69 years and 62% were male. The median length of stay was 6 days. The composite endpoint occurred in 106 patients and 154 patients within 30 and 60 days, respectively. Serum NGAL was more predictive than uNGAL and the uNGAL/uCr ratio but was not superior to sCr [area under the curve: admission sNGAL 0.61, 95% confidence interval (CI) 0.55-0.67, and 0.59, 95% CI 0.54-0.65; peak sNGAL: 0.60, 95% CI 0.54-0.66, and 0.57, 95% CI 0.52-0.63; admission sCr: 0.60, 95% CI 0.54-0.64, and 0.59, 95% CI 0.53-0.64; peak sCr: 0.61, 95% CI 0.55-0.67, and 0.59, 95% CI 0.54-0.64, at 30 and 60 days, respectively]. NGAL was not predictive of the composite endpoint in multivariate analysis. CONCLUSIONS: Serum NGAL outperformed uNGAL but neither was superior to admission or peak sCr for predicting adverse events.

Impact of risk factors of ischemic heart disease on the development of acute coronary syndrome, platelet ultrastructure, and aspirin resistance.

OBJECTIVE: Introduction: Risk factors of ischemic heart disease have an impact on blood cell apoptosis, platelets in particular, and their calcification. 5-40% of patients with high cardiovascular risk have anti-platelet drug resistance. The study of the morphofunctional status of platelets in patients with acute coronary syndrome is relevant and requires further research. The aim: to find out the impact of various risk factors for coronary heart disease on ultrastructural changes in platelets and the causes of their resistance to antiplatelet drugs. PATIENTS AND METHODS: Materials and methods: 36 patients with acute coronary syndrome and risk factors such as arterial hypertension, dyslipidemia, type 2 diabetes mellitus, smoking, alcohol abuse, and occupational hazards were examined. The mean age of patients was 56±5.6 years. The control group consisted of 10 apparently healthy people. Functional state and ultrastructure of platelets were studied using electron microscopy. RESULTS: Results: Most platelets of patients in the control group were discoid without pseudopods with evenly distributed platelet and dense granules. Platelets of patients with acute coronary syndrome were mostly activated, as evidenced by the presence of pseudopods, as well as moderate concentrations of platelet granules in their central region. In the study group of patients, part of platelets was aggregated, osmiophilic, and vacuolated with signs of microclasmatosis of the pseudopods. Particular attention should be paid to platelets with signs of calcification, as evidenced by their excessive osmiophilic property and manifestations of apoptosis. CONCLUSION: Conclusions: The presence of ischemic heart disease risk factors in acute coronary syndrome patients leads to platelet calcification and activation of blood cell apoptosis. With the use of electron microscopy, we detected degenerative changes of platelets and their calcification, which in the future may lead to the development of resistance to aspirin and require new oral coagulants.

B-type natriuretic peptide trend predicts clinical significance of worsening renal function in acute heart failure.

AIMS: In acute heart failure (AHF), relationships between changes in B-type natriuretic peptide (BNP) and worsening renal function (WRF) and its prognostic implications have not been fully determined. We investigated the relationship between WRF and a decrease in BNP with in-hospital and 1-year mortality in AHF. METHODS AND RESULTS: The Acute Kidney Injury NGAL Evaluation of Symptomatic heart faIlure Study (AKINESIS) was a prospective, international, multicentre study of AHF patients. Severe WRF (sWRF) was a sustained increase of ≥44.2 µmol/L (0.5 mg/dL) or ≥50% in creatinine, non-severe WRF (nsWRF) was a non-sustained increase of ≥26.5 µmol/L (0.3 mg/dL) or ≥50% in creatinine, and WRF with clinical deterioration was nsWRF with renal replacement therapy, inotrope use, or mechanical ventilation. Decreased BNP was defined as a ≥30% reduction in the last measured BNP compared to admission BNP. Among 814 patients, the incidence of WRF was not different between patients with or without decreased BNP (nsWRF: 33% vs. 31%, P = 0.549; sWRF: 11% vs. 9%, P = 0.551; WRF with clinical deterioration: 8% vs. 10%, P = 0.425). Decreased BNP was associated with better in-hospital and 1-year mortality regardless of WRF, while WRF was associated with worse outcomes only in patients without decreased BNP. In multivariate Cox regression analysis, decreased BNP, sWRF, and WRF with clinical deterioration were significantly associated with 1-year mortality. CONCLUSIONS: Decreased BNP was associated with better in-hospital and long-term outcomes. WRF was only associated with adverse outcomes in patients without decreased BNP.

Utility of Urine Neutrophil Gelatinase-Associated Lipocalin for Worsening Renal Function during Hospitalization for Acute Heart Failure: Primary Findings of the Urine N-gal Acute Kidney Injury N-gal Evaluation of Symptomatic Heart Failure Study (AKINESIS).

BACKGROUND: Worsening renal function (WRF) during acute heart failure (AHF) occurs frequently and has been associated with adverse outcomes, though this association has been questioned. WRF is now evaluated by function and injury. We evaluated whether urine neutrophil gelatinase-associated lipocalin (uNGAL) is superior to creatinine for prediction and prognosis of WRF in patients with AHF. METHODS AND RESULTS: We performed a multicenter, international, prospective cohort of patients with AHF requiring IV diuretics. The primary outcome was whether uNGAL predicted development of WRF, defined as a sustained increase in creatinine of 0.5 mg/dL or ≥50% above first value or initiation of renal replacement therapy, within the first 5 days. The main secondary outcome was a composite of in-hospital adverse events. We enrolled 927 patients (mean 68.5 years of age, 62% men). The primary outcome occurred in 72 patients (7.8%). The first, peak and the ratio of uNGAL to urine creatinine (area under curves (AUC) ≤ 0.613) did not have diagnostic utility over the first creatinine (AUC 0.662). There were 235 adverse events in 144 patients. uNGAL did not predict (AUCs ≤ 0.647) adverse clinical events better than creatinine (AUC 0.695). CONCLUSIONS: uNGAL was not superior to creatinine for predicting WRF or adverse in-hospital outcomes and cannot be recommended for WRF in AHF.