# Respiratory Viral Infections Today, Heart Failure Tomorrow: Implications for Prevention

Paul Loubet, François Roubille

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## To cite this version:

Paul Loubet, François Roubille. Respiratory Viral Infections Today, Heart Failure Tomorrow: Implications for Prevention. European Journal of Preventive Cardiology, 2025, pp.zwaf731. 10.1093/eur-jpc/zwaf731. hal-05365709

HAL Id: hal-05365709

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Submitted on 15 Feb 2026

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# Respiratory Viral Infections Today, Heart Failure Tomorrow: Implications for Prevention

Paul Loubet <fnref n="1" />, François Roubille <fnref n="2" />

<footnote n="1">¹ Virulence Bactérienne et Infections Chroniques, INSERM U1047, Univ Montpellier, Service des Maladies Infectieuses et Tropicales, CHU Nîmes, Nîmes, France.</footnote>

<footnote n="2">² Cardiology Department, INI-CRT, CHU de Montpellier, PhyMedExp, Université de Montpellier, INSERM, CNRS, 34295 Montpellier, France.</footnote>
The intersection between infectious diseases and cardiovascular outcomes has never been more pressing than in the post-COVID-19 pandemic era. Respiratory viral infections (RVIs)— including influenza, SARS-CoV-2, and respiratory syncytial virus (RSV)—are increasingly recognized for their acute respiratory manifestations potentially leading to acute cardiovascular (CV) decompensations and systemic, particularly CV, sequelae. In their recent contribution to the *European Journal of Preventive Cardiology*, Wee et al. present compelling data quantifying the medium-term risk of heart failure (HF) following hospitalization for RVIs using a large-scale, 1national cohort from Singapore (REF).

## RVI hospitalizations were linked to a 45% increased risk of new-onset HF

This retrospective cohort study included between 2017 and 2023 a total of 59,408 patients without pre-existing HF and 4,163 with established HF, comparing them to 137,000 matched controls hospitalized for orthopedic conditions. Using an advanced overlap-weighted competing risks regression approach, the study showed that RVI hospitalizations were linked to a 45% increased risk of new-onset HF in individuals previously unaffected (adjusted Hazard Ratio aHR 1.45; 95% CI: 1.26–1.67) and a 28% higher risk of HF readmission in those with existing HF (aHR 1.28; 95% CI: 1.08–1.52) over a 180-day follow-up period.

## RSV was a particularly high-risk pathogen

Stratified analyses showed that new-onset HF was most frequent after RSV infection (aHR 2.03, 95% CI: 1.26–3.25), followed by influenza (aHR 1.62, 95% CI: 1.28–2.06), and COVID-19 (aHR 1.36, 95% CI: 1.16–1.60). Notably, RSV was identified as a particularly high-risk pathogen, consistent with findings from a Canadian cohort study, which showed that RSV hospitalization was linked to a higher rate of subsequent HF events in older adults compared to those hospitalized for influenza or other non-infectious reasons (HR range 1.48–3.74). This increased risk was observed independently of pre-existing cardiovascular conditions [1]. Similarly, data from a retrospective study involving two hospital systems in Rochester, New York, indicated that hospitalization due to RSV elevates the risk of acute cardiovascular events, including HF, with the risk persisting for at least six months post-hospitalization [2].

The pathophysiology underpinning these observations likely involves both direct and indirect mechanisms. RVIs have been shown to induce myocardial inflammation, endothelial dysfunction, and systemic prothrombotic states. In the acute setting, myocardial injury has been frequently observed. In the FluHeart study, up to 75% of hospitalized influenza patients exhibited left ventricular dysfunction on echocardiography [3].

## Public health and practical impacts

These findings support routine cardiovascular risk assessments for patients aged 65 and older and emphasize the importance of robust vaccination policies, including flu, COVID-19, pneumococcal, and RSV vaccines, for this population.
Indeed, the most actionable insight from the study is the (CV) protective effect of vaccination. Among patients hospitalized for influenza, those vaccinated within the previous 365 days did not experience a significantly elevated HF risk. Similarly, among COVID-19 cases, receiving ≥4 vaccine doses or being vaccinated within 180 days of hospitalization was associated with no increased risk of HF readmission (HR 0.86 and 0.97, respectively).

These findings are highly consistent with the recent results of PANDA-2. This large, multi-center, cluster-randomized controlled trial in China showed that influenza vaccination among patients hospitalized for acute HF significantly reduced all-cause mortality and rehospitalization over 12 months [4].

Similarly, the DAN-RSV trial recently demonstrated that RSV vaccination in adults aged 60 years or older reduced both all-cause cardiorespiratory hospitalizations and HF-specific admissions [5], with consistent effects in participants with and without HF [6], thereby bolstering the argument for RSV vaccination as a cardiovascular prevention strategy.

Despite these encouraging results, vaccine uptake among patients with HF remains alarmingly low. In a French cohort of over 760,000 HF patients, only 63.1% received influenza vaccination, despite frequent primary and specialist care encounters [7].

Wee et al. correctly identify this gap as a missed preventive opportunity. As vaccination uptake remains inconsistent, especially among older adults or those with socioeconomic vulnerabilities [7], public health systems must consider bundled interventions that integrate vaccination with chronic disease management pathways—especially for those already diagnosed with HF.

This study makes a clear case: vaccination is not only a tool to prevent infection—it is a tool to prevent cardiovascular disease, specifically HF. In the context of rising RVI burden, an ageing population, and healthcare resource constraints, preventing even a fraction of HF events *via* vaccination could yield outsized returns in both economic and human terms.

**Vaccination should be considered a first-line cardiovascular preventive strategy in at risk populations, not merely an infectious disease intervention [8].**

**Disclosure statement**

P.L. has received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca, GSK, Janssen, Merck Sharp & Dohme, Moderna, Pfizer, Sanofi Pasteur, and Seqirus.

F.R. has received payment or honoraria for lectures, presentations, speaker bureaus, and educational events from AstraZeneca, Servier, Boehringer, Vifor, Bayer, Pfizer, Novartis,
Novo Nordisk, Air Liquide, Abbott, Quidel Ortho, Newcard, MSD, Sanofi, Alnylam, Zoll, Implicity, GSK, and BMS.

## Funding

None

## Author contribution

PL and FR drafted, critically reviewed the manuscript, and approved the version for publication.

## References

1. Verschoor CP, Cerasuolo JO, Caswell JM, Tatangelo M, Costa-Vitali A, Savage DW, Kwong JC. Respiratory Syncytial Virus (RSV)-Related Hospitalization and Increased Rate of Cardiovascular Events in Older Adults. J Am Geriatr Soc. 2025;73(9):2685-94

2. Sudnik P. Comprehensive Analysis of Cardiovascular Events and Risk Factors in Patients Hospitalized With Respiratory Syncytial Virus.

3. Skaarup KG, Davidovski FS, Durukan E, Modin D, Lassen MCH, Dons M, Jensen AMR, Johansen ND, Sengeløv M, Vyff F, Landler NE, Jensen GB, Nielsen AB, Christensen J, Hauser R, Schnohr P, Møgelvang R, Nielsen L, Jensen JS, Biering-Sørensen T. Cardiac Characteristics of Hospitalized Influenza Patients: An Interim Analysis From the FluHeart Study. Influenza Other Respir Viruses. févr 2025;19(2):e70067.

4. Anderson CS, Hua C, Wang Z, Wang C, Jiang C, Liu R, Han R, Li Q, Shan S, Billot L, Macintyre CR, Patel A, Zhang H, Ma C, Dong J, Du X. Influenza vaccination to improve outcomes for patients with acute heart failure (PANDA II): a multiregional, seasonal, hospital-based, cluster-randomised, controlled trial in China. The Lancet. 6 sept 2025;406(10507):1020-31.

5. Lassen MCH, Johansen ND, Christensen SH, Aliabadi N, Skaarup KG, Modin D, Claggett BL, Larsen CS, Larsen L, Wiese L, Dalager-Pedersen M, Lindholm MG, Jensen AMR, Dons M, Bernholm KF, Davidovski FS, Duus LS, Ottosen CI, Nielsen AB, Borchsenius JH, Espersen C, Köse G, Fussing FH, Pareek M, Køber L, Solomon SD, Jensen JUS, Martel CJM, Gessner BD, Schwarz C, Gonzalez E, Skovdal M, Moulton LH, Zhang P, Begier E, Biering-Sørensen T. Bivalent RSV Prefusion F Protein-Based Vaccine for Preventing Cardiovascular Hospitalizations in Older Adults: A Prespecified Analysis of the DAN- RSV Trial. JAMA. 28 oct 2025;334(16):1431-41.

6. Skaarup KG, Lassen MCH, Johansen ND, Christensen SH, Aliabadi N, Modin D, Claggett BL, Larsen CS, Larsen L, Wiese L, Dalager-Pedersen M, Lindholm MG, Jensen AMR, Dons M, Bernholm KF, Davidovski FS, Duus LS, Ottosen CI, Nielsen AB, Borchsenius JH, Espersen C, Köse G, Fussing FH, Køber L, Solomon SD, Jensen JUS, Martel CJM, Mebazaa A, Gessner BD, Schwarz C, Gonzalez E, Skovdal M, Zhang P, Begier E, Biering-Sørensen T. Effect of RSV Vaccine on Heart Failure Hospitalizations:
A Prespecified Analysis of the DAN-RSV Trial. J Am Coll Cardiol. 26 août 2025;S0735-1097(25)07467-4.
7. Roubille F, Wyplosz B, Fernandes J, Grenier B, Raguideau F, Blanc E, Goussiaume G. 1 Socioeconomic determinants of vaccination against pneumococcus in 763 945 2 patients with heart failure. ESC Heart Fail. oct 2025;12(5):3750-4. 3

8. Loubet P, Roubille F. Respiratory vaccines as cardiovascular prevention: evidence from 4 four landmark trials. Eur J Prev Cardiol. 14 oct 2025;zwaf671.
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