Influenza During Heart Failure Hospitalization Ups Death, Renal, Respiratory Risks

January 04, 2019

A new analysis documents just how much sicker an influenza infection can make patients who have been hospitalized with heart failure (HF), providing further argument for routinely offering flu vaccination to patients with HF after admission or in the community.

In the propensity-matched analysis involving more than 100,000 HF hospitalizations, the patients who also had the flu were not only more likely to die in hospital, they had much higher rates of acute respiratory failure, whether or not it required mechanical ventilation. Their risk of acute kidney injury, both with and without need for dialysis, was also significantly increased.

The associations between flu and mortality and other poor outcomes were strong "and certainly get us back to the drawing board when it comes to advocating influenza vaccinations for our patients," Ankur Kalra, MD, told | Medscape Cardiology.

Not surprisingly, hospital length of stay was also greater in the HF patients with flu infection, but their average hospital costs were similar to those in the group without the flu, observed Kalra, University Hospitals Cleveland Medical Center and Case Western Reserve University, Ohio, corresponding author on the analysis published January 2 in JACC: Heart Failure with lead author Muhammad S. Panhwar, MD, of the same institutions.

The analysis is based on more than 8 million records for adults hospitalized with HF in 2013 and 2014 in the National Inpatient Sample (NIS), a US database; they included 54,590 cases (0.67%) of patients who also had the flu.

Outcomes in the analysis didn't seem related to the type of hospital, for example, university-affiliated or small and community-based, Kalra observed. But it's possible they might have been different during years with other prevailing strains of influenza or flu vaccines with greater or lesser efficacy. Nor could it control for medical therapy administered during the hospitalizations, which wasn't captured in the database, he said.

"Although the exact extent to which influenza infection contributes to morbidity, and mortality in already-compromised patients with heart failure has been difficult to estimate, the results of this study make it clear that during the winter months this contribution is neither negligible nor neglectable," states an accompanying editorial.

"Despite a growing armamentarium for treating patients with heart failure, traditional therapies cannot modify this increased risk," write Orly Vardeny, PharmD, VA Health Care System, and the University of Minnesota, Minneapolis, and Scott D. Solomon, MD, Brigham and Women’s Hospital, Boston, Massachusetts.

Vaccination is the best way to mitigate the added risk from influenza in patients with heart failure, and "the strikingly low vaccination rates of some of our most vulnerable patients represent both a significant public health challenge and a substantial opportunity."

 Odds Ratios (OR) for Outcomes of HF Hospitalization by Influenza Status*

Endpoints With Flu
Infection, %
Without Flu
Infection, %
OR (95% CI); P value
In-Hospital Mortality 6.2 5.4 1.15 (1.03 - 1.30); .02
Acute Respiratory Failure 36.9 23.1 1.95 (1.83 - 2.07); < .001
ARF Requiring Mechanical
18.2 11.3 1.75 (1.62 - 1.89); < .001
Acute Kidney Injury 30.3 28.7 1.08 (1.02 - 1.15); .01
AKI Requiring Dialysis 2.4 1.8 1.37 (1.14 - 1.65); .001
*54,585 propensity-matched pairs of hospitalizations with HF, 2013-2014 data.
ARF, acute respiratory failure; AKI, acute kidney injury.

Hospital length of stay averaged 5.9 days for HF patients with the flu and 5.2 days for the matched HF patients without the flu (P < .001), although the mean hospital costs were similar at $12,137 and $12,003, respectively (P = .40).

There was no indication of how many patients received antiviral therapy or what effect it may have had, Kalra said, but "it would have been interesting to see whether concomitant administration of oseltamivir [Tamiflu] would have made a difference to any of the outcomes."

Kalra has disclosed consulting for Medtronic and Philips. Panhwar has reported no relevant relationships. Disclosures for the other authors are listed in the report. Vardeny has disclosed receiving research support from Sanofi Pasteur. Solomon reports receiving research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bristol-Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, the US National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and consulting for Akros, Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Cardior, Corvia, Cytokinetics, Gilead, GlaxoSmithKline, Ironwood, Merck, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, and Cardiac Dimensions.

JACC: Heart Failure. Published online January 2, 2018. Abstract, Editorial

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