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Therapies for Heart Failure: Clinical Updates and Perspectives

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: 20 June 2026 | Viewed by 5455

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Special Issue Editors

Dr. Cristina Tudoran

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1. Department VII, Internal Medicine II, Discipline of Cardiology, University of Medicine and Pharmacy "Victor Babes" Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
2. County Emergency Hospital "Pius Brinzeu", L. Rebreanu, Nr. 156, 300723 Timisoara, Romania
3. Center of Molecular Research in Nephrology and Vascular Disease, Faculty of the University of Medicine and Pharmacy "Victor Babes" Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
Interests: pulmonary hypertension; heart failure; heart rate variability; myocarditis; pericarditis; COVID-19; post-acute COVID-19 syndrome
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Dr. Stela Iurciuc

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Department of Cardiology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
Interests: rehabilitation in heart failure; risk prediction in cardiovascular disease; heart failure in patients with cancer; cardiovascular disease and autoimmune disease

Dr. Dragos Cozma

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1. Department of Cardiology, “Victor Babes” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania
2. Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
Interests: pacing; defibrillators; electrophysiology; echocardiography; heart failure; clinical cardiology; ECG
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Although the symptoms of heart failure (HF) have been recognized for decades, there is still disagreement among researchers regarding its clinical presentation and optimal therapeutic strategies. As societies evolve, the signs and symptoms of HF are also adapting, showing considerable variation across populations depending on race, ethnicity, cultural background, lifestyle, and the presence of comorbidities such as cancer or diabetes mellitus.

Clinical manifestations, along with associated comorbidities, significantly influence the progression of HF, compelling clinicians to tailor treatment plans and explore novel therapeutic avenues.

A recent breakthrough in HF management has been the development of new oral glucose-lowering agents, particularly sodium–glucose cotransporter-2 inhibitors (SGLT2i). This drug class has become a cornerstone of HF therapy, with ongoing research continually revealing additional benefits. At every major cardiology conference, innovative diagnostic techniques, clinical strategies for symptom relief, and a spectrum of treatment options—from new pharmacological agents to minimally invasive device implants and advanced cardiac surgery—are being presented and discussed.

This Special Issue will be dedicated to advancing our understanding of the etiology and management of HF. We welcome the submission of original research articles and reviews that align with this aim.

Dr. Cristina Tudoran
Dr. Stela Iurciuc
Prof. Dr. Dragos Cozma
Guest Editors

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Keywords

mechanisms of heart failure
new therapies for heart failure
chronic and acute heart failure
new approaches to managing heart failure patients
special populations
clinical outcome

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Published Papers (8 papers)

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18 pages, 1238 KB

Open AccessArticle

Prognostic Value of Inflammatory Status in Patients with Acute Coronary Syndromes: A Single-Center Experience

by Ruxandra-Maria Băghină, Simina Crișan, Silvia Luca, Oana Pătru, Mihai-Andrei Lazăr, Cristina Văcărescu, Marian Morenci, Alina-Gabriela Negru, Constantin-Tudor Luca and Dan Gaiță

J. Clin. Med. 2026, 15(8), 2852; https://doi.org/10.3390/jcm15082852 - 9 Apr 2026

Abstract

Background/Objectives: Acute coronary syndromes (ACS) encompass a spectrum of clinical entities from unstable angina to non–ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI), all associated with significant morbidity and mortality. Inflammation plays a central role in the pathophysiology of ACS, contributing to atherosclerotic plaque destabilization, myocardial injury, and adverse clinical outcomes. Inflammatory biomarkers, together with N-terminal pro–B-type natriuretic peptide (NT-proBNP), are increasingly used for risk stratification, yet their prognostic value across different ACS presentations remains unclear. This study aimed to assess the prognostic value of inflammatory status in patients with acute coronary syndromes in a single-center cohort. Methods: This prospective observational study included 100 consecutive patients with ACS and elevated inflammatory biomarkers, enrolled in 2024–2025 at a tertiary cardiovascular center. Inflammatory status was assessed by using C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII); NT-proBNP was also measured. The primary endpoint was in-hospital MACE, defined as cardiovascular death, recurrent myocardial infarction, stroke, urgent coronary revascularization, or acute heart failure requiring escalation of therapy. Multivariable logistic regression and ROC analyses were performed. Results: Among the 100 ACS patients, half experienced in-hospital MACE. Compared with those without events, patients with MACE were older (p = 0.003) and had higher inflammatory biomarkers—CRP (p < 0.001; strongest association), NLR (p = 0.030), and SII (p = 0.042)—as well as higher NT-proBNP (p = 0.002). Patients with MACE also showed reduced renal function (p < 0.001) and lower left ventricular systolic function, reflected by reduced LVEF (p = 0.001), indicating concomitant renal impairment and ventricular dysfunction. Hypertension was more prevalent in the MACE group (p = 0.028), and new-onset atrial fibrillation was significantly more common among these patients (p < 0.001). In multivariable analysis, LVEF emerged as an independent predictor of short-term outcomes (OR 0.934 per 1% increase; p = 0.047). Conclusions: Inflammatory activation appears closely linked to the occurrence of in-hospital adverse events in patients with acute coronary syndromes. While left ventricular ejection fraction remained an independent determinant of short-term outcomes, inflammatory biomarkers may provide complementary insight into the inflammatory burden accompanying ACS. Full article

(This article belongs to the Special Issue Therapies for Heart Failure: Clinical Updates and Perspectives)

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20 pages, 6748 KB

Open AccessArticle

Two-Year Implementation, Adherence, and Outcomes of Quadruple Guideline-Directed Medical Therapy in Newly Diagnosed HFrEF: Insights from the Prospective CaRD Registry

by Ivana Jurin, Daniel Lovrić, Karlo Gjuras, Šime Manola, Irzal Hadžibegović, Mario Udovičić, Diana Rudan, Anica Milinković, Jasmina Ćatić, Marija Križanović and Marin Pavlov

J. Clin. Med. 2026, 15(6), 2127; https://doi.org/10.3390/jcm15062127 - 11 Mar 2026

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Abstract

Background: Contemporary guidelines recommend rapid initiation of four classes of guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF); however, real-world persistence, adherence, and dose optimization remain suboptimal. Methods: We analysed a predefined subregistry within the prospective Cardiology Research Dubrava (CaRD) registry, a real-world HF registry at a tertiary centre that includes patients across the ejection-fraction spectrum in whom contemporary HF therapy, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), is introduced or optimised in routine practice. For this analysis, we included patients with newly diagnosed HFrEF (left ventricular ejection fraction (LVEF) ≤ 40%) who were discharged on all four GDMT classes; 167 of 179 patients with newly diagnosed HFrEF during the study period had an available 6-month medication assessment and comprised the final analytic cohort. The four GDMT pillars (beta-blocker; angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI); mineralocorticoid receptor antagonist (MRA); and SGLT2i) were initiated within 4 days when clinically feasible. Medication adherence and target-dose attainment were assessed at 6, 12, and 24 months using a structured self-report questionnaire. Major adverse events (MAE) and all-cause mortality were recorded over 24 months. Patients were classified as adherent if they reported regular intake (≥80% of prescribed doses) of all four drug classes at 6 months; otherwise, they were classified as nonadherent. Results: Among the 167 analysed patients (median age 64 years, 74% men, median LVEF 30%), regular adherence at 6, 12, and 24 months was 65%, 55%, and 59% for beta-blockers; 66%, 50%, and 49% for ACEi/ARB/ARNI; 62%, 52%, and 49% for MRAs; and 84%, 57%, and 68% for SGLT2i. Target doses were achieved in 25–33% for beta-blockers, 42–50% for ACEi/ARB/ARNI, and 73–78% for MRAs. At 24 months, 56 survivors (37%) were adherent to all four drug classes. Over 24 months, all-cause mortality was 9.0% and MAE 18.6%, occurring less frequently in adherent vs. nonadherent patients (mortality 0% vs. 13.5%; MAE 8.9% vs. 23.4%). Conclusions: In this real-world, non-randomized HFrEF subregistry, in-hospital initiation of quadruple GDMT was feasible, yet maintaining long-term adherence and achieving target doses remained challenging. These data underscore the gap between guideline recommendations and routine practice and support structured follow-up and protocol-driven titration to optimize implementation. Full article

(This article belongs to the Special Issue Therapies for Heart Failure: Clinical Updates and Perspectives)

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12 pages, 231 KB

Open AccessArticle

Increased Mortality and Complication Rates in Weekend Admissions for Acute Decompensated Heart Failure: A Five-Year National Study

by Hadi Itani, Mohammad Ennab, Mohamad Bahij Moumneh, Elie Bou Sanayeh, Elie Moussa, Bahy Abofrekha, Ahmed Zayed, Omar Khayat and Martin Amor

J. Clin. Med. 2026, 15(6), 2097; https://doi.org/10.3390/jcm15062097 - 10 Mar 2026

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Abstract

Background/Objectives: The “weekend effect,” characterized by increased mortality and complication rates for weekend hospital admissions, is well documented in myocardial infarction and stroke but has been less thoroughly investigated in acute decompensated heart failure (ADHF). This study evaluates the weekend effect in ADHF using a national cohort. Methods: A retrospective cohort study was conducted using the 2016–2020 Nationwide Inpatient Sample (NIS). Adult ADHF admissions were identified by ICD-10 codes and classified as weekend or weekday admissions. Over 30 variables, including age, sex, and comorbidities, were analyzed. Propensity score matching (1:1) yielded 489,204 patients per group. Univariate and multivariate logistic regression models were used to assess outcomes, adjusting for key covariates. Results: Of 2,131,915 ADHF hospitalizations, 501,076 (23.5%) occurred on weekends. The cohort was 48% female, with a mean age of 72 years (SD ± 12.3). After 1:1 matching, weekend admissions had higher odds of cardiac arrest (aOR: 1.10; 95% CI: 1.06–1.13, p < 0.001), inpatient mortality (aOR: 1.07; 95% CI: 1.05–1.09, p < 0.001), acute kidney injury (AKI; aOR: 1.07; 95% CI: 1.06–1.08, p < 0.001), and acute respiratory failure (ARF; aOR: 1.28; 95% CI: 1.27–1.30, p < 0.001). No significant differences were observed in mechanical circulatory support (MCS) use or length of stay. Conclusions: Weekend ADHF admissions were associated with a higher risk of mortality and complications, which may be attributable to reduced specialist availability or delayed diagnostics. These findings underscore the need for standardized ADHF protocols to ensure equitable care throughout the week. Full article

(This article belongs to the Special Issue Therapies for Heart Failure: Clinical Updates and Perspectives)

17 pages, 556 KB

Open AccessArticle

Pre-Existing Heart Failure, Biomarker Profiles, and Patients’ Vulnerability in Hospitalized COVID-19: A Biomarker-Driven Risk Framework

by Ana-Maria Pah, Maria-Laura Craciun, Adina Avram, Ruxandra Maria Christodorescu, Daian Ionel Popa, Simina Crisan, Cristina Vacarescu, Diana-Maria Mateescu, Dragos-Mihai Gavrilescu, Florina Buleu and Adrian-Cosmin Ilie

J. Clin. Med. 2026, 15(5), 1909; https://doi.org/10.3390/jcm15051909 - 3 Mar 2026

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Abstract

Background/Objectives: Heart failure (HF) has been associated with adverse outcomes in coronavirus disease 2019 (COVID-19), but it remains unclear whether HF independently predicts sepsis and mortality once inflammatory and cardiac biomarkers are considered. Methods: This single-center retrospective cohort analysis included 127 adult patients hospitalized with laboratory-confirmed COVID-19 at a tertiary infectious diseases hospital between March 2020 and December 2024. Pre-existing HF was defined based on cardiology records and chronic HF therapy. Baseline assessments included clinical characteristics, echocardiography, and biomarkers (NT-proBNP, high-sensitivity troponin, C-reactive protein [CRP], interleukin 6 [IL-6], procalcitonin, and D-dimer) measured within 24 h of admission. Primary outcomes were sepsis and all-cause mortality (in-hospital or 30-day). Independent associations with sepsis and mortality were examined using multivariable logistic regression incorporating demographic factors, major comorbidities, baseline disease severity, and inflammatory and cardiac biomarkers. Results: Of 127 patients (mean age 70.1 ± 14.8 years, 63.8% male), 30 (23.6%) had pre-existing HF. Patients with preexisting heart failure exhibited significantly reduced left ventricular ejection fraction and higher admission levels of NT-proBNP and high-sensitivity troponin, accompanied by a substantially increased burden of in-hospital cardiovascular complications (53.3% vs. 14.4%, p < 0.001). However, sepsis (6.7% vs. 7.2%, p = 1.000) and total mortality (20.0% vs. 17.5%, p = 0.971) did not differ significantly between HF and non-HF groups. In multivariable analyses, HF was not independently associated with sepsis (adjusted odds ratio [aOR] 0.78, 95% confidence interval [CI] 0.05–12.34, p = 0.855) or mortality (aOR 0.63, 95% CI 0.16–2.46, p = 0.506). By contrast, higher CRP (aOR 1.01 per 1 mg/L, 95% CI 1.00–1.01, p = 0.007), IL-6 (aOR 1.01 per 1 pg/mL, 95% CI 1.00–1.01, p = 0.025), and high-sensitivity troponin (aOR >999, 95% CI 138–>999, p = 0.001) were independently associated with mortality. Conclusions: In hospitalized COVID-19 patients, pre-existing HF identifies a subgroup with heightened cardiac biomarker activation and a substantially higher burden of cardiovascular complications but does not associate with sepsis or short-term mortality in this cohort after adjustment for inflammatory and cardiac biomarkers. Mortality risk appears to be driven primarily by systemic inflammation and acute myocardial injury, as reflected by CRP, IL-6, and high-sensitivity troponin. These findings support a biomarker-driven approach to risk stratification in COVID-19, in which dynamic inflammatory and cardiac injury profiles provide more prognostic information than HF status alone, while still warranting intensified cardiovascular surveillance in patients with HF. Full article

(This article belongs to the Special Issue Therapies for Heart Failure: Clinical Updates and Perspectives)

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16 pages, 702 KB

Open AccessArticle

Combined Burden of Heart Failure and Arterial Hypertension as Predictors of Adverse Outcomes in Hospitalized COVID-19 Patients

by Ana-Maria Pah, Ana-Olivia Toma, Camelia-Oana Muresan, Diana-Maria Mateescu, Ioana-Georgiana Cotet, Luchian Iancu-Ciorbagiu, Adrian-Cosmin Ilie, Daian Ionel Popa, Dragos-Mihai Gavrilescu, Stela Iurciuc, Maria-Laura Craciun, Simina Crisan and Adina Avram

J. Clin. Med. 2026, 15(3), 1143; https://doi.org/10.3390/jcm15031143 - 2 Feb 2026

Cited by 1 | Viewed by 416

Abstract

Background: Cardiovascular comorbidities are major determinants of poor outcomes among patients admitted with COVID-19. However, the prognostic role of arterial hypertension alone remains uncertain. Little is known about the cumulative impact of concomitant hypertension and heart failure. This study assessed whether the combined burden of arterial hypertension and pre-existing heart failure identifies a high-risk phenotype for adverse in-hospital outcomes among COVID-19 patients. Methods: In this retrospective, real-world cohort study, 395 consecutive adults hospitalized with confirmed COVID-19 at a single infectious diseases center between March 2020 and December 2024 were included. We categorized patients into three cardiovascular phenotype groups: no hypertension or heart failure (n = 23), hypertension without heart failure (n = 193), and concomitant hypertension and heart failure (n = 178). The primary outcome was in-hospital all-cause mortality, while ICU admission served as a secondary outcome, invasive mechanical ventilation, and length of hospital stay. Multivariable logistic regression included age, sex, BMI, diabetes mellitus, and vaccination status to evaluate independent associations between the cardiovascular risk group and outcomes. Results: Overall in-hospital mortality was 7.3% (29/395). Mortality increased stepwise across the cardiovascular risk groups: 8.7% in patients without hypertension or heart failure, 3.1% in those with hypertension only, and 11.8% in patients with concomitant hypertension and heart failure (p = 0.004). In adjusted analyses, concomitant hypertension and heart failure were linked to higher adjusted odds of in-hospital death than no cardiovascular disease (odds ratio, 3.49; 95% confidence interval, 1.46–8.35). Isolated hypertension was not significantly associated with mortality. ICU admission and length of hospital stay also increased with cumulative cardiovascular burden. Patients with combined hypertension and heart failure showed more pronounced inflammatory and renal abnormalities at admission. Conclusions: Among hospitalized COVID-19 patients, the coexistence of arterial hypertension and heart failure identifies a vulnerable cardiovascular phenotype associated with higher in-hospital mortality and resource use than either no cardiovascular disease or hypertension alone. These findings support evaluating cardiovascular comorbidities cumulatively rather than in isolation. These findings are exploratory and require external validation in independent, larger multicentre cohorts. Findings may support careful use for short-term risk stratification and closer monitoring strategies during COVID-19 hospitalization. Full article

(This article belongs to the Special Issue Therapies for Heart Failure: Clinical Updates and Perspectives)

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12 pages, 914 KB

Open AccessArticle

The Impact of Introducing Sacubitril/Valsartan and SGLT2 Inhibitors in a Cohort of Patients with Reduced-Ejection-Fraction Heart Failure: A Real-Life Observational Study

by Andrea López-López, Margarita Regueiro-Abel, Charigan Abou Johk-Casas, José María Vieitez-Flórez, Juliana Elices-Teja, Jorge Armesto-Rivas, Gonzalo de Urbano-Seara, Alejandro Manuel López-Pena, Carmen Cristina Álvarez-Suárez, Gema Rois-González, Germán Santamarina-Pernas and Carlos González-Juanatey

J. Clin. Med. 2026, 15(3), 991; https://doi.org/10.3390/jcm15030991 - 26 Jan 2026

Viewed by 576

Abstract

Background/Objectives: Reduced-ejection-fraction heart failure (HFrEF) constitutes a challenge due to its high morbidity and mortality. The use of sacubitril/valsartan (angiotensin receptor–neprilysin inhibitors [ARNI]) and SGLT2 inhibitors (SGLT2i) represents a change in management approach with a demonstrated association with positive ventricular remodeling and a reduction in cardiovascular events. We describe the clinical and therapeutic course of patients with HFrEF in a specialized unit, comparing two consecutive periods (2011–2016 vs. 2017–2021), with emphasis on the impact of ARNI and SGLT2i upon clinical parameters and the use of devices. Methods: A retrospective, longitudinal observational study was carried out in 1363 outpatients with HFrEF, with at least two years of follow-up. Clinical characteristics, treatments, the evolution of left ventricular ejection fraction (LVEF), mortality, and the use of devices (implantable cardioverter–defibrillator [ICD], cardiac resynchronization therapy [CRT]) were evaluated. Results: A total of 1363 patients were analyzed, showing a significant therapeutic change in the 2017–2021 group with the incorporation of ARNI (40%) and SGLT2i (25%). This cohort achieved better ventricular recovery, with a significantly higher mean LVEF at one year compared to the 2011–2016 group (44.3% vs. 42.1%; p = 0.004). Regarding devices, ICD implantation rate decreased in the recent period (7.2% vs. 11.1%; p = 0.016), while CRT indication increased. Most importantly, all-cause mortality after two years fell from 9.4% to 5.9% (p = 0.023). Multivariate analysis confirmed that this survival improvement was independently associated with the study period (HR 1.57 for the earlier group) and was linked to the protective effect of contemporary pharmacological treatments. Conclusions: The systematic introduction of ARNI and SGLT2i in the treatment of HFrEF was associated with improved ventricular function, reduced need for device implantation, and lower mortality over the middle term in a real-life clinical setting. Full article

(This article belongs to the Special Issue Therapies for Heart Failure: Clinical Updates and Perspectives)

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24 pages, 2703 KB

Open AccessSystematic Review

Effects of SGLT2 Inhibitors on Clinical Outcomes, Symptoms, Functional Capacity, and Cardiac Remodeling in Heart Failure: A Comprehensive Systematic Review and Multidomain Meta-Analysis of Randomized Trials

by Olivia-Maria Bodea, Stefania Serban, Maria-Laura Craciun, Diana-Maria Mateescu, Eduard Florescu, Camelia-Oana Muresan, Ioana-Georgiana Cotet, Marius Badalica-Petrescu, Andreea Munteanu, Dana Velimirovici, Nilima Rajpal Kundnani and Simona Ruxanda Dragan

J. Clin. Med. 2026, 15(1), 378; https://doi.org/10.3390/jcm15010378 - 4 Jan 2026

Viewed by 1373

Abstract

Background: SGLT2 inhibitors are key therapies in heart failure (HF), but their combined multidomain effects have not been analyzed together. Methods: We conducted a PROSPERO-registered (CRD420251235850) systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing SGLT2i (dapagliflozin, empagliflozin, canagliflozin, sotagliflozin) with placebo in adults with HF, regardless of ejection fraction or diabetes status. We searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, and Web of Science through 1 February 2025. Outcomes were grouped into four domains: (1) clinical events, (2) symptoms/health status (Kansas City Cardiomyopathy Questionnaire, KCCQ), (3) functional capacity (6 min walk distance, peak VO₂), and (4) cardiac remodeling/energetics (cardiac MRI, 31P-MRS). We used random-effects models with Hartung–Knapp adjustment and assessed heterogeneity by I² and prediction intervals. Results: Eleven RCTs with 23,812 patients (HFrEF, HFmrEF, HFpEF, and acute or recently decompensated HF) were included. SGLT2i lowered the risk of cardiovascular death or first HF hospitalization by 23% (HR 0.77, 95% CI 0.72–0.82; p < 0.0001; I² = 28%; prediction interval 0.68–0.87), with similar effects across ejection fraction, diabetes status, and presentation type. All-cause and cardiovascular mortality dropped by 12% (HR 0.88, 95% CI 0.81–0.96) and 14% (HR 0.86, 95% CI 0.78–0.95), respectively. SGLT2i improved KCCQ—Clinical Summary Score by 4.6 points (95% CI 3.4–5.8; p < 0.0001) and increased the odds of a ≥5-point improvement (OR 1.49, 95% CI 1.32–1.68; NNT = 12). Six-minute walk distance increased by 21.8 m (95% CI 9.4–34.2; p = 0.001), and mechanistic trials showed significant reverse remodeling (ΔLVEDV −19.8 mL, ΔLVEF +6.1%; both p < 0.001). No improvement was observed in myocardial PCr/ATP ratio. Safety was favorable, with no excess ketoacidosis or severe hypoglycemia. Conclusions: This multidomain synthesis demonstrates that SGLT2 inhibitors provide consistent, robust reductions in mortality and hospitalizations, while also delivering early, clinically meaningful improvements across multiple patient-centered domains. These results establish SGLT2i as a foundational component of contemporary HF management. Full article

(This article belongs to the Special Issue Therapies for Heart Failure: Clinical Updates and Perspectives)

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21 pages, 2057 KB

Open AccessSystematic Review

Systemic Inflammatory Biomarkers (Interleukin-6, High-Sensitivity C-Reactive Protein, and Neutrophil-to-Lymphocyte Ratio) and Prognosis in Heart Failure: A Meta-Analysis of Prospective Cohort Studies

by Ana-Maria Pah, Stefania Serban, Diana-Maria Mateescu, Ioana-Georgiana Cotet, Camelia-Oana Muresan, Adrian-Cosmin Ilie, Florina Buleu, Maria-Laura Craciun, Simina Crisan and Adina Avram

J. Clin. Med. 2025, 14(23), 8610; https://doi.org/10.3390/jcm14238610 - 4 Dec 2025

Cited by 1 | Viewed by 1590

Abstract

Background: Systemic inflammation plays a pivotal role in heart failure (HF) progression, yet no meta-analysis has synthesized prospective cohort data on interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers. Objectives: To quantify the independent prognostic value of IL-6, hs-CRP, and NLR for mortality and HF-related outcomes across HF phenotypes. Methods: Following PRISMA and MOOSE guidelines, we searched PubMed, Embase, Scopus, Web of Science, and CENTRAL from January 2014 to October 2025 for prospective cohorts reporting adjusted hazard ratios (HRs). Random-effects meta-analysis pooled HRs; heterogeneity was assessed via I² statistic, with subgroup and sensitivity analyses for robustness. Quality was evaluated using Newcastle–Ottawa Scale (NOS) and GRADE. Results: Thirteen cohorts (n ≈ 19,000) were included. Elevated IL-6 (five studies) was associated with increased all-cause mortality and composite outcomes (low-moderate heterogeneity, I² < 35%). hs-CRP (five studies) showed similar prognostic strength, with trajectories amplifying risk. NLR (three studies) independently predicted adverse events with negligible heterogeneity. Associations persisted across HFrEF and HFpEF, acute/chronic settings, and geographic regions, independent of natriuretic peptides and comorbidities (NOS median 8/9; GRADE moderate-to-high). Conclusions: IL-6, hs-CRP, and NLR are robust, independent prognostic biomarkers in HF, supporting their integration into clinical risk stratification and inflammation-targeted therapies. PROSPERO: CRD420251207035. Full article

(This article belongs to the Special Issue Therapies for Heart Failure: Clinical Updates and Perspectives)

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