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Clinical Updates in Heart Failure: Innovations in Diagnosis, Therapy and Management

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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: 28 August 2026 | Viewed by 4376

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Dr. Paolo Severino

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Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Interests: heart failure pathophysiology; advanced heart failure; cardiovascular imaging; hemodynamics and congestion assessment; guideline-directed medical therapy; digital health and remote HF care

Special Issue Information

Dear Colleagues,

Heart failure (HF) remains one of the most challenging cardiovascular conditions, with rising prevalence and persistently high clinical impact worldwide. Rapid advances in diagnostics, imaging, therapeutics, and digital health are offering unique opportunities to refine risk stratification, improve decongestion strategies, and personalize HF management across the disease spectrum.

This Special Issue, Clinical Updates in Heart Failure: Innovations in Diagnosis, Therapy and Management, aims to highlight innovative developments in HF care. We welcome original research and review articles focused on novel diagnostic tools, emerging pharmacological and device-based therapies, congestion and hemodynamic assessment, and cardiorenal interactions.

Topics of interest include the following

Diagnostic innovations and HF phenotyping;
GDMT optimization and therapeutic sequencing;
HFpEF, HFmrEF and right ventricular dysfunction therapies;
Imaging advances and congestion assessment;
Cardiorenal syndrome and comorbidity management;
Digital health personalized care.

We warmly invite your contributions to this Special Issue.

Dr. Paolo Severino
Guest Editor

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Keywords

heart failure
HFrEF therapy
HFpEF phenotyping
right ventricular dysfunction
renal congestion assessment
diuretic resistance
NT-proBNP dynamics
cardiac imaging
post-discharge management

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Published Papers (7 papers)

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16 pages, 879 KB

Open AccessArticle

Hyperuricemia Reflects Cardiometabolic Burden Rather than Left Ventricular Systolic Dysfunction Across Heart Failure Phenotypes: Insights from a Real-World Acute Heart Failure Cohort

by Raluca Ibănescu, Sebastian Ciurescu, Roxana Buzaș, Anda Gabriela Militaru, Diana-Alexandra Mîțu, Loredana Nicoleta Ionică, Iacob-Daniel Goje, Ciprian Rachieru, Paul-Gabriel Ciubotaru, Vlad Sabin Ivan, Daian-Ionel Popa and Daniel-Florin Lighezan

J. Clin. Med. 2026, 15(14), 5719; https://doi.org/10.3390/jcm15145719 - 21 Jul 2026

Viewed by 284

Abstract

Background/Objectives: Acute heart failure (AHF) is a leading cause of global morbidity, necessitating the search for reliable biomarkers to guide risk stratification. While hyperuricemia is highly prevalent in heart failure patients and historically considered a potential “cardiotoxin”, contemporary evidence suggests that it may function as a surrogate biomarker for cardiometabolic distress rather than an independent driver of myocardial dysfunction. This study aimed to determine whether serum uric acid acts as an independent predictor of left ventricular ejection fraction (LVEF) in a high-risk cardiometabolic cohort. Methods: This retrospective, cross-sectional study analyzed 306 patients hospitalized for acute heart failure at a tertiary hospital in Timisoara, Romania. Data were analyzed using JASP (v0.96). Statistical methods included Shapiro–Wilk testing, Spearman’s rank-order correlation, and independent samples t-tests. Multivariable ordinary least squares linear regression and maximum likelihood logistic regression were employed to identify predictors of LVEF and diagnostic classification, adjusting for comorbidities and diuretic administration. Results: Hyperuricemia was present in 64.6% of the cohort. Multivariable linear regression demonstrated that while age, sex, and diuretic use significantly predicted LVEF variance, serum uric acid did not (p = 0.356). Furthermore, logistic regression confirmed uric acid possessed no diagnostic utility in differentiating heart failure phenotypes (OR = 0.995; p = 0.973). Conclusions: Serum uric acid is not an independent predictor of reduced ejection fraction in acute heart failure patients. Elevated uric acid appears to be a biochemical shadow of generalized metabolic distress, systemic congestion, and the pharmacokinetic effects of diuretic therapy rather than a pathological driver of contractile dysfunction. Full article

(This article belongs to the Special Issue Clinical Updates in Heart Failure: Innovations in Diagnosis, Therapy and Management)

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14 pages, 5961 KB

Open AccessArticle

Association of Sleep Duration Ratio with a Reduced Risk of Heart Failure: Analysis of the 2017–2023 National Health and Nutrition Examination Survey

by Narathorn Kulthamrongsri, Thanathip Suenghataiporn, Adivitch Sripusanapan, Smuch Siramongkholkarn, Thitiphan Srikulmontri, Chanokporn Puchongmart, Thanaboon Yinadsawaphan, Ben Thiravetyan, Kridhitach Ngarmukos, Koravich Lorlowhakarn, Nathasith Tangprasittichok, Abdulelah Nuqali and Ekamol Tantisattamo

J. Clin. Med. 2026, 15(13), 5047; https://doi.org/10.3390/jcm15135047 - 29 Jun 2026

Viewed by 363

Abstract

Background/Objectives: In the United States, HF prevalence is projected to progressively rise by 2030. Prior research suggests a strong association between reduced sleep duration and increased cardiovascular disease and HF risk. This study introduces an alternative parameter, the weekend sleep recovery (WSR), measured by the weekend-to-weekday sleep duration ratio (SDR), to evaluate its association with HF risk. Methods: We conducted a cross-sectional analysis of NHANES (National Health and Nutrition Examination Survey) 2017–2023 to examine self-reported sleep patterns. Participants were classified as WSR (SDR > 1) or non-WSR (SDR ≤ 1). Multivariate logistic regression assessed the association between WSR and HF, adjusting for demographics and comorbidities. Results: Among 8320 participants included in the fully adjusted analysis, WSR was associated with lower odds of HF compared with non-WSR (adjusted OR 0.73, 95% CI 0.55–0.96; p = 0.026). A significant interaction was observed between WSR and weekday sleep duration (P for interaction = 0.003), whereas no interaction was found with weekend sleep duration. In exploratory subgroup analyses, nominally significant associations were observed in several clinical subgroups; however, after correction for multiple comparisons, only participants without dyslipidemia retained statistical significance. No significant effect modification by race/ethnicity was observed (P for interaction = 0.436). Conclusions: Weekend sleep recovery was associated with lower odds of HF in this cross-sectional study. The association varied according to weekday sleep duration but was generally consistent across racial/ethnic groups. Given the observational design, these findings should be interpreted as associative rather than causal and warrant confirmation in prospective studies. Full article

(This article belongs to the Special Issue Clinical Updates in Heart Failure: Innovations in Diagnosis, Therapy and Management)

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23 pages, 8679 KB

Open AccessArticle

Sacubitril/Valsartan Improves Functional Capacity and Reverses LV Remodeling in Obese Patients with Hypertrophic HFpEF: A Randomized Open-Label Study

by Artem Ovchinnikov, Alexandra Potekhina, Anastasiya Shchendrygina, Olga Svirida, Maria Sobolevskaya, Zoya Blankova, Maria Glezer and Fail Ageev

J. Clin. Med. 2026, 15(11), 4286; https://doi.org/10.3390/jcm15114286 - 1 Jun 2026

Viewed by 698

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) has multiple phenotypic manifestations with heterogeneous treatment responses. Objective: To evaluate the effect of sacubitril/valsartan (Sac/Val) on functional capacity and cardiac remodeling in overweight/obese HFpEF patients with concentric left ventricular hypertrophy (LVH). Methods: Sixty-one overweight/obese HFpEF patients (body mass index ≥ 25 kg/m²) with hypertensive LVH (LV mass index ≥ 115 g/m² for men or ≥94 g/m² for women) were randomized to Sac/Val (100–400 mg a day; n = 30) versus the usual care group (n = 31) for 6 months. Changes in six-minute walk test distance (6MWTD) were the primary outcomes. Secondary outcomes included changes in echocardiographic parameters of cardiac structure and function, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Results: After 6 months of Sac/Val therapy, 6MWTD increased, and E/e′ ratio, LV mass index, LA volume index, and NT-proBNP levels decreased compared with the usual care group (p < 0.05 for all). Conclusions: In overweight/obese patients with HFpEF and LVH, Sac/Val significantly improved functional capacity and reduced LV mass and filling pressure compared with standard medical therapy. Full article

(This article belongs to the Special Issue Clinical Updates in Heart Failure: Innovations in Diagnosis, Therapy and Management)

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27 pages, 1434 KB

Open AccessFeature PaperArticle

Prognostic Role of Immunonutritional Indices in Elderly Patients with HFpEF: Long-Term Follow-Up of the CONUT, PNI, and CALLy Scores

by Andrea Sonaglioni, Chiara Lonati, Andrea Donzelli, Federico Napoli, Gian Luigi Nicolosi, Massimo Baravelli, Michele Lombardo and Sergio Harari

J. Clin. Med. 2026, 15(9), 3245; https://doi.org/10.3390/jcm15093245 - 24 Apr 2026

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Abstract

Background: Malnutrition and systemic inflammation are increasingly recognized as important determinants of prognosis in patients with heart failure. Several immunonutritional indices, including the Prognostic Nutritional Index (PNI), the Controlling Nutritional Status (CONUT) score, and the C-reactive protein–albumin–lymphocyte (CALLy) index, have been proposed as markers of nutritional and inflammatory status. However, their prognostic value in elderly patients with heart failure with preserved ejection fraction (HFpEF) remains incompletely defined. This study aimed to evaluate the prognostic significance of these immunonutritional indices in elderly patients with HFpEF over a long-term follow-up period. Methods: This retrospective observational study included 200 elderly patients hospitalized with HFpEF (mean age 86.6 ± 6.5 years). Clinical, laboratory, and echocardiographic parameters were collected at admission. Nutritional status was assessed using PNI, CONUT score, and CALLy index. Patients were followed for mortality during long-term follow-up. Survival analyses were performed using Cox regression models, receiver operating characteristic (ROC) curves, and Kaplan–Meier analysis. Median follow-up was 3.8 years (IQR 2.1–5.9). Results: During follow-up, 123 patients (61.5%) died, while 77 patients (38.5%) were alive at the end of observation. In univariate analysis, PNI, CONUT score, left ventricular ejection fraction (LVEF), and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure (TAPSE/sPAP) ratio were significantly associated with mortality. In multivariate analysis, the CONUT score, LVEF, and the TAPSE/sPAP ratio remained independent predictors of mortality. ROC analysis showed strong prognostic performance for the TAPSE/sPAP ratio (AUC 0.932), CONUT score (AUC 0.925), and LVEF (AUC 0.897). Optimal cut-off values for mortality prediction were CONUT ≥ 6, LVEF ≥ 65%, and TAPSE/sPAP ≤ 0.55 mm/mmHg. Kaplan–Meier analysis confirmed significantly reduced survival among patients with higher CONUT scores, higher LVEF, and an impaired TAPSE/sPAP ratio. Conclusions: In elderly patients with HFpEF, nutritional status and cardiopulmonary functional parameters are important determinants of long-term prognosis. The CONUT score emerged as the most informative immunonutritional index, while echocardiographic parameters reflecting ventricular function and right ventricular–pulmonary arterial coupling provided additional prognostic information. Integrating nutritional assessment with echocardiographic evaluation may improve risk stratification in elderly patients with HFpEF. Full article

(This article belongs to the Special Issue Clinical Updates in Heart Failure: Innovations in Diagnosis, Therapy and Management)

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18 pages, 2299 KB

Open AccessArticle

Uric Acid Variability Is Associated with Poor Prognosis in Heart Failure

by Viana Copeland, Shir Elimeleh, Assi Milwidsky, Noam Makmal, Ranel Loutati, Boris Fishman, Yishay Wasserstrum, Moti Zwilling, Elad Maor and Ehud Grossman

J. Clin. Med. 2026, 15(6), 2330; https://doi.org/10.3390/jcm15062330 - 18 Mar 2026

Viewed by 723

Abstract

Aims: Elevated uric acid (UA) levels correlate with worse heart failure (HF) outcomes, but past studies used single UA measurements. The effect of intra-individual UA fluctuations, beyond mean levels, is unclear. This study assesses the relationship between serum UA variability and adverse clinical outcomes in HF patients. Methods: We analyzed 18,115 HF patients from the SHEBAHEART registry (2009–2025) with at least three UA measurements within three years of diagnosis. UA variability was quantified as the mean deviation (MD) from each patient’s average UA level and divided into quartiles: Q1 (≤−0.69 mg/dL), Q2–Q3 (>−0.69 and <1.53 mg/dL, reference), and Q4 (≥1.53 mg/dL). All-cause mortality was the primary outcome and HF hospitalization was secondary. Cox regression, propensity score matching, and subgroup analyses were used. Results: Over a median follow-up of 4.3 years (IQR 1.6–7.7), 36% of patients were hospitalized for HF and 65.5% died. UA variability showed a graded association with outcomes. Low variability (Q1) was linked to reduced mortality (HR 0.79, 95% CI 0.75–0.83) and HF hospitalization (HR 0.84, 95% CI 0.79–0.90), while high variability (Q4) increased mortality (HR 1.58, 95% CI 1.51–1.69) and hospitalization risk (HR 1.17, 95% CI 1.10–1.25) (all p < 0.001). These associations remained after propensity score matching and across HF subgroups. Conclusions: UA variability is a robust, independent predictor of mortality and HF hospitalization. Serial UA monitoring may enhance risk stratification in HF management. Full article

(This article belongs to the Special Issue Clinical Updates in Heart Failure: Innovations in Diagnosis, Therapy and Management)

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11 pages, 250 KB

Open AccessEditor’s ChoiceArticle

Differences in Scalp Hair Trace Element Concentrations in Patients with Preserved Left Ventricular Ejection Fraction (HFpEF) Compared with Controls: A Hypothesis-Generating Study

by Tomasz Urbanowicz, Anetta Hanć, Zofia Kasperowicz, Oliwier Adamczak, Ievgen Spasanenko, Katarzyna Gabriel, Andrzej Tykarski, Zbigniew Krasiński and Beata Krasińska

J. Clin. Med. 2026, 15(5), 2029; https://doi.org/10.3390/jcm15052029 - 6 Mar 2026

Cited by 2 | Viewed by 600

Abstract

Background: The pathophysiology of HFpEF is complex and characterized by systemic inflammation, metabolic dysregulation, and endothelial dysfunction. Trace element involvement in redox balance, mitochondrial function, and calcium signaling is postulated. This cross-sectional analysis aimed to investigate possible differences in hair scalp trace element concentrations in patients with HFpEF and controls. Material and methods: Fifty-eight consecutive patients were enrolled (HFpEF n = 37; controls n = 21). HFpEF diagnosis was established using the HFA-PEFF diagnostic algorithm by two independent cardiologists blinded to hair analysis results. Scalp hair samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Results: HFpEF patients demonstrated higher hair concentrations of magnesium (17.8 (7.3–47.5) vs. 14.0 (6.7–29.0) µg/g, p = 0.037), copper (57.24 (33.87–84.76) vs. 12.96 (9.85–26.02) µg/g, p < 0.001), calcium (322 (106–1330) vs. 145 (74–672) µg/g, p = 0.006), and lead (0.257 (0.164–0.563) vs. 0.159 (0.079–0.283) µg/g, p = 0.03). Conclusions: In this exploratory analysis, HFpEF was associated with differences in selected scalp hair trace element concentrations. The interaction between magnesium, calcium, copper, and lead were noted, with higher concentrations in HFpEF phenotypes. These findings are hypothesis-generating and warrant confirmation in larger cohorts incorporating serum/urine measurements and exposure assessment. Full article

(This article belongs to the Special Issue Clinical Updates in Heart Failure: Innovations in Diagnosis, Therapy and Management)

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27 pages, 2058 KB

Open AccessSystematic Review

Heart Failure with Supranormal Ejection Fraction: An Emerging High-Risk Phenotype Within the Preserved Ejection Fraction Spectrum—A Systematic Review

by Andrea Sonaglioni, Giulio Francesco Gramaglia, Gian Luigi Nicolosi, Massimo Baravelli, Michele Lombardo and Italo Porto

J. Clin. Med. 2026, 15(14), 5361; https://doi.org/10.3390/jcm15145361 - 9 Jul 2026

Viewed by 369

Abstract

Background: Heart failure with supranormal ejection fraction (HFsnEF) has recently emerged as a distinct phenotype within the preserved ejection fraction spectrum. However, its clinical profile, underlying mechanisms, and prognostic significance remain incompletely understood. Methods: A systematic review was conducted according to PRISMA recommendations. PubMed, Scopus, and EMBASE were searched from inception to May 2026 for studies investigating HFsnEF. Demographic, clinical, laboratory, echocardiographic, prognostic, and therapeutic data were extracted. Weighted descriptive analyses were performed to compare HFsnEF and conventional heart failure with preserved ejection fraction (HFpEF) populations. Random-effects meta-analyses of study-specific event rates were conducted for all-cause mortality and for the composite endpoint of cardiovascular death or heart failure hospitalization. Results: Fourteen studies involving 17,158 HFpEF patients and 7493 HFsnEF patients were included. Compared with HFpEF, HFsnEF patients exhibited broadly similar clinical, laboratory, haemodynamic, and treatment profiles, with a higher prevalence of women and a lower prevalence of coronary artery disease representing the most consistent clinical differences. Conventional laboratory parameters and natriuretic peptide concentrations showed substantial overlap between groups. Echocardiographically, HFsnEF was characterized by significantly smaller left ventricular end-systolic dimensions and volumes and higher ejection fraction despite similar stroke volume and cardiac output. Mechanistic studies further demonstrated significantly higher end-systolic elastance and lower ventriculo-arterial coupling ratios despite comparable arterial elastance, supporting the presence of distinct ventricular–vascular mechanical properties. Prognostic analyses consistently identified HFsnEF as a phenotype associated with adverse clinical outcomes. Pooled event-rate analyses demonstrated significantly higher rates of both all-cause mortality and the composite endpoint of cardiovascular death or heart failure hospitalization in HFsnEF compared with HFpEF. Emerging evidence also suggests a potential benefit of sodium–glucose cotransporter-2 inhibitors in this population. Conclusions: HFsnEF appears to represent a distinct and potentially high-risk phenotype within the preserved ejection fraction spectrum. Its characteristic structural, haemodynamic, and prognostic features challenge the traditional assumption that progressively higher ejection fraction necessarily reflects better cardiovascular health. Further prospective studies incorporating advanced imaging and haemodynamic assessment are needed to refine its pathophysiological characterization and therapeutic management. Full article

(This article belongs to the Special Issue Clinical Updates in Heart Failure: Innovations in Diagnosis, Therapy and Management)

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