Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 14 min ago
Peer-reviewedCC BY 4.0Frontiers in Cardiovascular Medicine

Beyond the trigger: the unknown precipitant as a high-risk phenotype in acute heart failure

  • Georgios Aletras1,2
  • Maria Bachlitzanaki3
  • Maria Stratinaki1
  • Emmanuel Lamprogiannakis1
  • Emmanuel Foukarakis1
  • Yannis Pantazis4
  • Michalis Hamilos2,5
  • Kostas Stylianou2,6
6 affiliations
  1. 1Department of Cardiology, Venizelio General Hospital of Heraklion
  2. 2School of Medicine, University of Crete
  3. 3Second Department of Internal Medicine, Venizelio General Hospital of Heraklion
  4. 4Institution of Applied and Computational Mathematics, Foundation of Research and Technology-Hellas
  5. 5Department of Cardiology, University General Hospital of Heraklion
  6. 6Department of Nephrology, University General Hospital of Heraklion
Open at sourceDOICite

Abstract

Background: A substantial proportion of patients with acute heart failure (AHF) present without an identifiable precipitating factor. We compared the clinical profile, echocardiographic characteristics, and mid-term outcomes of AHF patients stratified by precipitating factor category.

Methods: We conducted a prospective single-center observational study at Venizelio General Hospital, Heraklion, including 486 consecutive patients hospitalized with AHF between February 2023 and January 2025. Patients were classified into three groups: behavioral ( n = 148), non-behavioral/clinical ( n = 230), and unknown ( n = 108). The primary endpoint was all-cause death at 12 months; secondary endpoints were terminal renal replacement therapy (RRT) and a composite of death, AHF rehospitalization or RRT. Groups were compared by Kaplan–Meier analysis and Cox regression with the behavioral group as reference, and the cumulative incidence of first AHF rehospitalization was estimated with death and terminal RRT as competing events.

Results: The unknown group was older and more frail (CFS ≥5), with more advanced chronic kidney disease, more right heart failure and lower TAPSE, higher NT-proBNP and lower admission eGFR. All-cause mortality at 12 months was 41.7% versus 20.3% and 29.6% (log-rank p < 0.001; unknown vs. behavioral HR 2.44, 95% CI 1.54–3.88), with a parallel gradient for the composite endpoint (event-free survival 35.2% vs. 58.8% and 52.6%; HR 1.96, 1.39–2.77). After adjustment for age, admission eGFR, right heart failure, NT-proBNP and frailty, precipitant category no longer improved model fit (likelihood ratio p = 0.066) and the association of the unknown group with mortality was attenuated and no longer significant (adjusted HR 1.43, 0.88–2.31). With death and terminal RRT as competing events, 12-month cumulative incidence of first AHF rehospitalization did not differ (36.1% vs. 29.7% and 26.1%; p = 0.207). ACEi/ARB prescription at discharge was lower in the unknown group (21.2% vs. 39.0% and 44.2%, p < 0.001).

Conclusions: In AHF, the absence of an identifiable precipitating factor identifies a high-risk phenotype characterized by advanced multimorbidity, right ventricular dysfunction, renal impairment and worse mid-term outcomes. The difference was driven predominantly by mortality rather than rehospitalization, and the association was attenuated after adjustment for the phenotype-defining variables. The label may therefore serve as an early bedside marker of advanced disease, requiring confirmation in multicenter cohorts.

Related

  1. Prognostic Models to Trigger Palliative Care Referrals in Heart Failure: A Scoping Review
    Klara Whalen, Hilary Bews, James W. Tam +2
    CJC openPeer-reviewedCC BYFull textCardiovascular medicineEurope PMC
  2. Presumed right atrial myxoma causing mechanical inflow obstruction and a heart-failure-with-preserved-ejection-fraction–mimicking phenotype in a resource-limited setting: A case report
    Radiology case reportsPeer-reviewedCC BY-NC-NDFull textGeneral medicineEurope PMC
  3. Neutrophil-to-Lymphocyte Ratio Identifies a Pulmonary Vascular High-Risk Phenotype in Heart Failure with Preserved Ejection Fraction
    M. Bril, E. Parnasa, A. Sufian +3
    medRxivPreprintAll rights reservedFull textCardiovascular medicinemedRxiv
  4. Diet Composition Modifies Cardiometabolic Phenotype Development in the 4-Vinylcyclohexene Dioxide (VCD) Ovarian Failure Model of Menopause
    Natalia M. Mathieu, Samuel B.R. Lawton, Margaret M. Dorrington +11
    American journal of physiology. Regulatory, integrative and comparative physiologyPeer-reviewedCC BYFull textEndocrinology & metabolismPMC
  5. Beyond Eosinophilia: A Dual Eosinophil Phenotype Model in Bronchiectasis
    Hasret Gizem Kurt, Ayperi Öztürk, Zeynep Erayman Özen +2
    Medicina (Kaunas, Lithuania)Peer-reviewedCC BYFull textGeneral medicineEurope PMC

Cite

BibTeXRIS
BibTeX
@article{aletras2026beyond,
  title = {{Beyond the trigger: the unknown precipitant as a high-risk phenotype in acute heart failure}},
  author = {Georgios Aletras and Maria Bachlitzanaki and Maria Stratinaki and Emmanuel Lamprogiannakis and Emmanuel Foukarakis and Yannis Pantazis and Michalis Hamilos and Kostas Stylianou},
  journal = {Frontiers in Cardiovascular Medicine},
  year = {2026},
  month = oct,
  doi = {10.3389/fcvm.2026.1880740},
  url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1880740/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Beyond the trigger: the unknown precipitant as a high-risk phenotype in acute heart failure
AU  - Georgios Aletras
AU  - Maria Bachlitzanaki
AU  - Maria Stratinaki
AU  - Emmanuel Lamprogiannakis
AU  - Emmanuel Foukarakis
AU  - Yannis Pantazis
AU  - Michalis Hamilos
AU  - Kostas Stylianou
PY  - 2026
DA  - 2026/10/30
JO  - Frontiers in Cardiovascular Medicine
DO  - 10.3389/fcvm.2026.1880740
UR  - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1880740/full
AB  - Background: A substantial proportion of patients with acute heart failure (AHF) present without an identifiable precipitating factor. We compared the clinical profile, echocardiographic characteristics, and mid-term outcomes of AHF patients stratified by precipitating factor category.  Methods: We conducted a prospective single-center observational study at Venizelio General Hospital, Heraklion, including 486 consecutive patients hospitalized with AHF between February 2023 and January 2025. Patients were classified into three groups: behavioral ( n = 148), non-behavioral/clinical ( n = 230), and unknown ( n = 108). The primary endpoint was all-cause death at 12 months; secondary endpoints were terminal renal replacement therapy (RRT) and a composite of death, AHF rehospitalization or RRT. Groups were compared by Kaplan–Meier analysis and Cox regression with the behavioral group as reference, and the cumulative incidence of first AHF rehospitalization was estimated with death and terminal RRT as competing events.  Results: The unknown group was older and more frail (CFS ≥5), with more advanced chronic kidney disease, more right heart failure and lower TAPSE, higher NT-proBNP and lower admission eGFR. All-cause mortality at 12 months was 41.7% versus 20.3% and 29.6% (log-rank p < 0.001; unknown vs. behavioral HR 2.44, 95% CI 1.54–3.88), with a parallel gradient for the composite endpoint (event-free survival 35.2% vs. 58.8% and 52.6%; HR 1.96, 1.39–2.77). After adjustment for age, admission eGFR, right heart failure, NT-proBNP and frailty, precipitant category no longer improved model fit (likelihood ratio p = 0.066) and the association of the unknown group with mortality was attenuated and no longer significant (adjusted HR 1.43, 0.88–2.31). With death and terminal RRT as competing events, 12-month cumulative incidence of first AHF rehospitalization did not differ (36.1% vs. 29.7% and 26.1%; p = 0.207). ACEi/ARB prescription at discharge was lower in the unknown group (21.2% vs. 39.0% and 44.2%, p < 0.001).  Conclusions: In AHF, the absence of an identifiable precipitating factor identifies a high-risk phenotype characterized by advanced multimorbidity, right ventricular dysfunction, renal impairment and worse mid-term outcomes. The difference was driven predominantly by mortality rather than rehospitalization, and the association was attenuated after adjustment for the phenotype-defining variables. The label may therefore serve as an early bedside marker of advanced disease, requiring confirmation in multicenter cohorts.
SN  - 2297-055X
ER  -