Journal of Clinical Medicine

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7 pages, 1436 KiB

Open AccessArticle

Soluble Isoform of Suppression of Tumorigenicity 2 (ST2) Biomarker in a Large Cohort of Healthy Pediatric Population: Determination of Reference Intervals

by Marco Alfonso Perrone, Julien Favresse, Annamaria D’Alessandro, Federica Albanese, Coralie De Bruyne, Stefano Ceccarelli, Fabrizio Drago, Paolo Guccione, Ottavia Porzio and Benedetta Leonardi

J. Clin. Med. 2022, 11(16), 4693; https://doi.org/10.3390/jcm11164693 - 11 Aug 2022

Cited by 5 | Viewed by 1507

Abstract

Introduction: Only little data exists on ST2 reference intervals in healthy pediatric populations despite the high importance of this biomarker in adults with heart failure. The aim of the study was to assess the reference intervals of ST2 in a wide healthy pediatric [...] Read more.

Introduction: Only little data exists on ST2 reference intervals in healthy pediatric populations despite the high importance of this biomarker in adults with heart failure. The aim of the study was to assess the reference intervals of ST2 in a wide healthy pediatric cohort. Methods: We evaluated the serum concentrations of ST2 biomarker in 415 healthy pediatric subjects referred to our analysis laboratory. Subjects were categorized according to age (i.e., 0–6 (n = 79), 7–11 (n = 142) and 12–18 years (n = 191)) and sex. They were not suffering from any cardiac disorders, metabolic disorders, lung diseases, autoimmune disorders or malignancies. A written consent was obtained for each individual. No duplicate patients were included in the analysis and the presence of outliers was investigated. Reference intervals (Mean and central 95% confidence intervals) were determined. Results: Three outliers have been identified and removed from the analysis (60.0, 64.0 and 150.2 ng/mL). A total of 412 subjects were therefore included. The mean value for the whole population was 15.8 ng/mL (2.4–36.4 ng/mL). Males present a significantly higher mean concentration compared to females (17.2 versus 14.4 ng/mL, p = 0.001). A significant trend toward higher ST2 values with age was also observed, but for males only (r = 0.43, p < 0.0001). If considering age partitions, only males of 12–18 years (mean = 21.7 ng/mL) had significantly higher ST2 values compared to the other groups (ranging from 11.9 for males 0–6 years to 15.2 for females 12–18 years; p < 0.0001). Conclusions: We described age and sex-specific reference intervals for ST2 in a large healthy pediatric population. We found that ST2 values differ between sexes if considering all participants. A significant increase in ST2 with age was also observed, but only for males of 12–18 years. Full article

(This article belongs to the Special Issue Novel Biomarkers in Heart Failure)

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17 pages, 1912 KiB

Open AccessArticle

Serum Liberation of Fetal Fibronectin Variants in Patients with Pulmonary Hypertension: ED-A⁺ Fn as Promising Novel Biomarker of Pulmonary Vascular and Right Ventricular Myocardial Remodeling

by Laura Bäz, Michelle Roßberg, Katja Grün, Daniel Kretzschmar, Alexander Berndt, P. Christian Schulze, Christian Jung and Marcus Franz

J. Clin. Med. 2021, 10(12), 2559; https://doi.org/10.3390/jcm10122559 - 9 Jun 2021

Cited by 2 | Viewed by 2245

Abstract

Background and Aims: Pulmonary Hypertension (PH) represents an aetiologically and clinically heterogeneous disorder accompanied by a severely impaired prognosis. Key steps of PH pathogenesis are vascular and right ventricular myocardial remodelling entailing the re-occurrence of fetal variants of the cell adhesion modulating protein [...] Read more.

Background and Aims: Pulmonary Hypertension (PH) represents an aetiologically and clinically heterogeneous disorder accompanied by a severely impaired prognosis. Key steps of PH pathogenesis are vascular and right ventricular myocardial remodelling entailing the re-occurrence of fetal variants of the cell adhesion modulating protein fibronectin (Fn) being virtually absent in healthy adult tissues. These variants are liberated into circulation and are therefore qualified as excellent novel serum biomarkers. Moreover, these molecules might serve as promising therapeutic targets. The current study was aimed at quantifying the serum levels of two functionally important fetal Fn variants (ED-A⁺ and ED-B⁺ Fn) in patients suffering from PH due to different aetiologies compared to healthy controls. Methods: Serum levels of ED-A⁺ and ED-B⁺ Fn were quantified using novel ELISA protocols established and validated in our group in 80 PH patients and 40 controls. Results were analysed with respect to clinical, laboratory, echocardiographic and functional parameters. Results: Serum levels of ED-A⁺ Fn (p = 0.001) but not ED-B⁺ Fn (p = 0.722) were significantly increased in PH patients compared to healthy controls. Thus, the following analyses were performed only for ED-A⁺ Fn. When dividing PH patients into different aetiological groups according to current ESC guidelines, the increase in ED-A⁺ Fn in PH patients compared to controls remained significant for group 1 (p = 0.032), 2 (p = 0.007) and 3 (p = 0.001) but not for group 4 (p = 0.156). Correlation analysis revealed a significant relation between ED-A⁺ Fn and brain natriuretic peptide (BNP) (r = 0.310; p = 0.002), six minutes’ walk test (r = −0.275; p = 0.02) and systolic pulmonary artery pressure (PAPsys) (r = 0.364; p < 0.001). By logistic regression analysis (backward elimination WALD) including a variety of potentially relevant patients’ characteristics, only chronic kidney disease (CKD) (OR: 8.866; CI: 1.779–44.187; p = 0.008), C reactive protein (CRP) (OR: 1.194; CI: 1.011–1.410; p = 0.037) and ED-A⁺ Fn (OR: 1.045; CI: 1.011–1.080; p = 0.009) could be identified as independent predictors of the presence of PH. Conclusions: Against the background of our results, ED-A⁺ Fn could serve as a promising novel biomarker of PH with potential value for initial diagnosis and aetiological differentiation. Moreover, it might contribute to more precise risk stratification of PH patients. Beyond that, the future role of ED-A⁺ Fn as a therapeutic target has to be evaluated in further studies. Full article

(This article belongs to the Special Issue Novel Biomarkers in Heart Failure)

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7 pages, 357 KiB

Open AccessArticle

Stay Home! Stay Safe! First Post-Discharge Cardiologic Evaluation of Low-Risk–Low-BNP Heart Failure Patients in COVID-19 Era

by Nadia Aspromonte, Luigi Cappannoli, Pietro Scicchitano, Francesco Massari, Ivan Pantano, Massimo Massetti, Filippo Crea and Roberto Valle

J. Clin. Med. 2021, 10(10), 2126; https://doi.org/10.3390/jcm10102126 - 14 May 2021

Cited by 6 | Viewed by 1991

Abstract

Background. The COVID-19 pandemic has had a deep impact on periodic outpatient evaluations. The aim of this study was to evaluate the impact of low brain natriuretic peptide (BNP) values in predicting adverse events in heart failure (HF) patients in order to evaluate [...] Read more.

Background. The COVID-19 pandemic has had a deep impact on periodic outpatient evaluations. The aim of this study was to evaluate the impact of low brain natriuretic peptide (BNP) values in predicting adverse events in heart failure (HF) patients in order to evaluate implications for safe delay of outpatient visits. Methods. This was a retrospective study. One-thousand patients (mean age: 72 ± 10 years, 561 women) with HF and BNP values <250 pg/mL at discharge were included. A 6-month follow-up was performed. The primary endpoint was a combination of deaths and readmissions for HF within 6-month after discharge. Results. At 6-month follow-up, 104 events (10.4%) were recorded (65 HF readmissions and 39 all-cause deaths). Univariate Cox analysis identified as significant predictors of outcome were age (p < 0.001, hazard ratio [HR] = 1.044), creatinine (p = 0.001, HR = 1.411), and BNP (p < 0.001, HR = 1.010). Multivariate Cox regression confirmed that BNP (p < 0.001, HR = 1.009), creatinine (p = 0.016, HR = 1.247), and age (p = 0.013, HR = 1.027) were independent predictors of events in HF patients with BNP values <250 pg/mL at discharge. Patients with BNP values >100 pg/mL and creatinine >1.0 mg/dL showed increased events rates (from 4.3% to 19.0%) as compared to those with lower values (p < 0.000, HR = 4.014). Conclusions. Low pre-discharge BNP levels were associated with low rates of cardiovascular events in HF patients, independently of the frequency of follow-up. Full article

(This article belongs to the Special Issue Novel Biomarkers in Heart Failure)

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10 pages, 974 KiB

Open AccessArticle

Mitochondrial Biomarkers in Patients with ST-Elevation Myocardial Infarction and Their Potential Prognostic Implications: A Prospective Observational Study

by Nicola Cosentino, Jeness Campodonico, Marco Moltrasio, Claudia Lucci, Valentina Milazzo, Mara Rubino, Monica De Metrio, Ivana Marana, Marco Grazi, Alice Bonomi, Fabrizio Veglia, Gianfranco Lauri, Antonio L. Bartorelli and Giancarlo Marenzi

J. Clin. Med. 2021, 10(2), 275; https://doi.org/10.3390/jcm10020275 - 13 Jan 2021

Cited by 3 | Viewed by 1779

Abstract

Background: Mitochondrial biomarkers have been investigated in different critical settings, including ST-elevation myocardial infarction (STEMI). Whether they provide prognostic information in STEMI, complementary to troponins, has not been fully elucidated. We prospectively explored the in-hospital and long-term prognostic implications of cytochrome c and [...] Read more.

Background: Mitochondrial biomarkers have been investigated in different critical settings, including ST-elevation myocardial infarction (STEMI). Whether they provide prognostic information in STEMI, complementary to troponins, has not been fully elucidated. We prospectively explored the in-hospital and long-term prognostic implications of cytochrome c and cell-free mitochondrial DNA (mtDNA) in STEMI patients undergoing primary percutaneous coronary intervention. Methods: We measured cytochrome c and mtDNA at admission in 466 patients. Patients were grouped according to mitochondrial biomarkers detection: group 1 (−/−; no biomarker detected; n = 28); group 2 (−/+; only one biomarker detected; n = 283); group 3 (+/+; both biomarkers detected; n = 155). A composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema was the primary endpoint. Four-year all-cause mortality was the secondary endpoint. Results: Progressively lower left ventricular ejection fractions (52 ± 8%, 49 ± 8%, 47 ± 9%; p = 0.006) and higher troponin I peaks (54 ± 44, 73 ± 66, 106 ± 81 ng/mL; p = 0.001) were found across the groups. An increase in primary (4%, 14%, 19%; p = 0.03) and secondary (10%, 15%, 23%; p = 0.02) endpoint rate was observed going from group 1 to group 3. The adjusted odds ratio increment of the primary endpoint from one group to the next was 1.65 (95% CI 1.04–2.61; p = 0.03), while the adjusted hazard ratio increment of the secondary endpoint was 1.55 (95% CI 1.12–2.52; p = 0.03). The addition of study group allocation to admission troponin I reclassified 12% and 22% of patients for the primary and secondary endpoint, respectively. Conclusions: Detection of mitochondrial biomarkers is common in STEMI and seems to be associated with in-hospital and long-term outcome independently of troponin. Full article

(This article belongs to the Special Issue Novel Biomarkers in Heart Failure)

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Review

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10 pages, 1264 KiB

Open AccessReview

Prognostic Value of sST2 in Heart Failure

by Edoardo Sciatti, Anna Merlo, Claudio Scangiuzzi, Raul Limonta, Mauro Gori, Emilia D’Elia, Alberto Aimo, Giuseppe Vergaro, Michele Emdin and Michele Senni

J. Clin. Med. 2023, 12(12), 3970; https://doi.org/10.3390/jcm12123970 - 11 Jun 2023

Cited by 8 | Viewed by 2412

Abstract

In recent years, there has been growing interest in the risk stratification for heart failure, and the use of multiple biomarkers to identify different pathophysiological processes associated with this condition. One such biomarker is soluble suppression of tumorigenicity-2 (sST2), which has shown some [...] Read more.

In recent years, there has been growing interest in the risk stratification for heart failure, and the use of multiple biomarkers to identify different pathophysiological processes associated with this condition. One such biomarker is soluble suppression of tumorigenicity-2 (sST2), which has shown some potential for integration into clinical practice. sST2 is produced by both cardiac fibroblasts and cardiomyocytes in response to myocardial stress. Other sources of sST2 are endothelial cells of the aorta and coronary arteries and immune cells such as T cells. Indeed, ST2 is also associated with inflammatory and immune processes. We aimed at reviewing the prognostic value of sST2 in both chronic and acute heart failure. In this setting, we also provide a flowchart about its potential use in clinical practice. Full article

(This article belongs to the Special Issue Novel Biomarkers in Heart Failure)

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16 pages, 1182 KiB

Open AccessReview

Brain Natriuretic Peptide Biomarkers in Current Clinical and Therapeutic Scenarios of Heart Failure

by Gianmarco Alcidi, Giovanni Goffredo, Michele Correale, Natale Daniele Brunetti and Massimo Iacoviello

J. Clin. Med. 2022, 11(11), 3192; https://doi.org/10.3390/jcm11113192 - 2 Jun 2022

Cited by 19 | Viewed by 4408

Abstract

Brain natriuretic peptide (BNP) and its inactive N-terminal fragment, NT-proBNP, are serum biomarkers with key roles in the management of heart failure (HF). An increase in the serum levels of these peptides is closely associated with the pathophysiological mechanisms underlying HF such as [...] Read more.

Brain natriuretic peptide (BNP) and its inactive N-terminal fragment, NT-proBNP, are serum biomarkers with key roles in the management of heart failure (HF). An increase in the serum levels of these peptides is closely associated with the pathophysiological mechanisms underlying HF such as the presence of structural and functional cardiac abnormalities, myocardial stretch associated with a high filling pressure and neuro-hormonal activation. As BNP and NT-proBNP measurements are possible, several studies have investigated their clinical utility in the diagnosis, prognostic stratification, monitoring and guiding therapy of patients with HF. BNP and NT-proBNP have also been used as criteria for enrollment in randomized trials evaluating the efficacy of new therapeutic strategies for HF. Nevertheless, the use of natriuretic peptides is still limited in clinical practice due to the controversial aspect of their use in different clinical settings. The purpose of this review is to discuss the main issues associated with using BNP and NT-proBNP serum levels in the management of patients with HF under current clinical and therapeutic scenarios. Full article

(This article belongs to the Special Issue Novel Biomarkers in Heart Failure)

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10 pages, 2298 KiB

Open AccessReview

Basal Septal Hypertrophy as the Early Imaging Biomarker for Adaptive Phase of Remodeling Prior to Heart Failure

by Fatih Yalçin, Hulya Yalçin, Nagehan Küçükler, Serbay Arslan, Oguz Akkuş, Alparslan Kurtul and Maria Roselle Abraham

J. Clin. Med. 2022, 11(1), 75; https://doi.org/10.3390/jcm11010075 - 24 Dec 2021

Cited by 8 | Viewed by 4026

Abstract

Hypertension plays a dominant role in the development of left ventricular (LV) remodeling and heart failure, in addition to being the main risk factor for coronary artery disease. In this review, we focus on the focal geometric and functional tissue aspects of the [...] Read more.

Hypertension plays a dominant role in the development of left ventricular (LV) remodeling and heart failure, in addition to being the main risk factor for coronary artery disease. In this review, we focus on the focal geometric and functional tissue aspects of the LV septal base, since basal septal hypertrophy (BSH), as the early imaging biomarker of LV remodeling due to hypertensive heart disease, is detected in cross-sectional clinic studies. In addition, the validation of BSH by animal studies using third generation microimaging and relevant clinical observations are also discussed in the report. Finally, an evaluation of both human and animal quantitative imaging studies and the importance of combined cardiac imaging methods and stress-induction in the separation of adaptive and maladaptive phases of the LV remodeling are pointed out. As a result, BSH, as the early imaging biomarker and quantitative follow-up of functional analysis in hypertension, could possibly contribute to early treatment in a timely fashion in the prevention of hypertensive disease progression to heart failure. A variety of stress stimuli in etiopathogenesis and the difficulty of diagnosing pure hemodynamic overload mediated BSH lead to an absence of the certain prevalence of this particular finding in the population. Full article

(This article belongs to the Special Issue Novel Biomarkers in Heart Failure)

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13 pages, 746 KiB

Open AccessReview

Biomarkers in Cardiorenal Syndrome

by Giovanni Goffredo, Roberta Barone, Vito Di Terlizzi, Michele Correale, Natale Daniele Brunetti and Massimo Iacoviello

J. Clin. Med. 2021, 10(15), 3433; https://doi.org/10.3390/jcm10153433 - 31 Jul 2021

Cited by 24 | Viewed by 5679

Abstract

Cardiorenal syndrome is a clinical manifestation of the bidirectional interaction between the heart and kidney diseases. Over the last years, in patients with cardiovascular diseases, several biomarkers have been studied in order to better assess renal function as well as to identify patients [...] Read more.

Cardiorenal syndrome is a clinical manifestation of the bidirectional interaction between the heart and kidney diseases. Over the last years, in patients with cardiovascular diseases, several biomarkers have been studied in order to better assess renal function as well as to identify patients prone to experiencing chronic or acute worsening of renal function. The aim of this review is to focus on the possible clinical usefulness of the most recent biomarkers in the setting of cardiorenal syndrome. Full article

(This article belongs to the Special Issue Novel Biomarkers in Heart Failure)

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14 pages, 718 KiB

Open AccessReview

Novel Biomarkers in Heart Failure: New Insight in Pathophysiology and Clinical Perspective

by Luigi Marzio Biasucci, Alessandro Maino, Maria Chiara Grimaldi, Luigi Cappannoli and Nadia Aspromonte

J. Clin. Med. 2021, 10(13), 2771; https://doi.org/10.3390/jcm10132771 - 24 Jun 2021

Cited by 24 | Viewed by 4381

Abstract

Heart failure (HF) is a complex clinical syndrome with a huge social burden in terms of cost, morbidity, and mortality. Brain natriuretic peptide (BNP) appears to be the gold standard in supporting the daily clinical management of patients with HF. Novel biomarkers may [...] Read more.

Heart failure (HF) is a complex clinical syndrome with a huge social burden in terms of cost, morbidity, and mortality. Brain natriuretic peptide (BNP) appears to be the gold standard in supporting the daily clinical management of patients with HF. Novel biomarkers may supplement BNP to improve the understanding of this complex disease process and, possibly, to personalize care for the different phenotypes, in order to ameliorate prognosis. In this review, we will examine some of the most promising novel biomarkers in HF. Inflammation plays a pivotal role in the genesis and progression of HF and, therefore, several candidate molecules have been investigated in recent years for diagnosis, prognosis, and therapy monitoring. Noncoding RNAs are attractive as biomarkers and their potential clinical applications may be feasible in the era of personalized medicine. Given the complex pathophysiology of HF, it is reasonable to expect that the future of biomarkers lies in the application of precision medicine, through wider testing panels and “omics” technologies, to further improve HF care delivery. Full article

(This article belongs to the Special Issue Novel Biomarkers in Heart Failure)

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