Many Invasive Procedures, Including Cardiovascular, Up Risk of Infective Endocarditis

With a design enabling patients to serve as their own controls, a large, Swedish study is reopening the debate over prophylactic antibiotics.

Many Invasive Procedures, Including Cardiovascular, Up Risk of Infective Endocarditis

A Swedish study spanning 14 years of hospital records is strengthening the argument that numerous types of invasive medical procedures—everything from surgery to blood transfusion—do, in fact, increase the risk of infective endocarditis.

CABG, which was associated with a nearly 14-fold increase in the relative risk of the life-threatening condition, ranked among the top five riskiest inpatient procedures. Angioplasty was linked to a more than tripled risk, while various categories of inpatient and outpatient interventions, including angiography, also appeared to open the door to infection.

Starting in the 1950s, antibiotics were commonly given to patients slated for dental and medical procedures in the hopes of killing off bacteria, Martin H. Thornhill, MBBS, BDS, PhD (University of Sheffield School of Clinical Dentistry, England), and colleagues point out in an editorial accompanying the new results, which were published online ahead of the June 19, 2018, issue of the Journal of the American College of Cardiology.

“Indeed, prior to 2007, US and European guidelines recommended antibiotic prophylaxis before a wide range of invasive medical procedures,” they say. But thanks to “lack of definitive evidence,” the editorialists note, the recommendations were downgraded to target only high-risk patients undergoing invasive dental procedures.

In their new report, Imre Janszky, MD, PhD (Norwegian University of Science and Technology, Trondheim, Norway), and colleagues attempt to fill in that evidence gap by using a case-crossover design.

For their nationwide study, the researchers looked only at people in Sweden who developed endocarditis, checking to see whether they’d had an invasive procedure in the previous 12 weeks or in a corresponding 12-week period 1 year prior. The within-person comparisons, with each individual acting as his or her own control, mean that the findings “are unlikely to be confounded by stable patient characteristics like chronic underlying cardiac conditions, chronic immune compromised conditions, or stable lifestyle-related factors” that up might up the risk of infective endocarditis, they explain.

Pointing out to TCTMD in an email that the current study does not look directly at any potential effects of antibiotics, Janszky also cautioned that it doesn’t offer insight into which patients might benefit from them or which procedures might merit their use.

That said, the “findings should be considered by those making future guidelines. However, making a guideline is a complex process, and our results have to be viewed in light of other studies with different designs and settings [with attention to] cost-benefit considerations,” he advised.

Outpatient and Inpatient

Janszky et al excluded dental procedures, since these were not captured in the hospital data set, as well as procedures likely done to address existing infections, which might have muddied interpretation.

There were 7,013 cases of endocarditis in Swedish hospitals between 1998 and 2011. Most patients were men (64.2%), and the mean age was 64.6 years. Patients classified as high risk—due to having a previous episode of infective endocarditis, a cardiac valve, cyanotic congenital heart disease that was unrepaired or treated with palliative shunts or conduits, or a prior transplant—made up 14.9% of the cohort.

Invasive medical procedures were indeed more common in the 12 weeks ahead of endocarditis than they’d been the year prior (24.0% vs 6.9%). Dozens of outpatient and inpatient procedures were linked to significantly increased risk.

Procedures Associated With Endocarditis Risk: Top Five



95% CI








Coronary Angiography






Bone Marrow Puncture










Other CV Therapeutic Procedures*






Intracranial and Cranial Procedures



*Surgeries of the aorta and large arteria, open heart surgeries, minor cardiac surgeries, and insertion of a pacemaker or defibrillator

Percutaneous transluminal coronary angioplasty, though not in the top five, was linked to higher risk of endocarditis (RR 3.50; 95% CI 1.41-8.67). Skin and wound management procedures also seemed particularly risky, but the difference did not meet statistical significance (RR 7.00; 95% CI 0.86-56.89).

The researchers estimated that, overall, 476 high-risk patients would need to receive antibiotics ahead of an inpatient procedure in order to prevent one case of infective endocarditis within the next 12 weeks, though numbers were lower for higher-risk procedures. “Because these calculations assume that antibiotic prophylaxis provides a perfect protection, which is unlikely, the real number of patients needed to be treated is [likely] somewhat higher,” they note.

Not Just About Antibiotics

Apart from antibiotics, other measures might also be protective, Janszky et al write. “Healthcare professionals performing particularly risk-prone procedures should consider every possible preventive measure to decrease the excess risk. Furthermore, increased awareness of the heightened risk in the vulnerable period after these procedures might lead to earlier diagnosis with a better chance for successful therapy and for avoiding the feared complications of the disease.”

The editorialists, while cautioning that even such a carefully designed observational study can’t prove causality, say the findings can guide future research.

“If the breadth of procedures associated with increased risk is confirmed by further studies, this will raise important questions for guideline committees about the benefits of recommending antibiotic prophylaxis prior to some of these procedures,” Thornhill and colleagues write.

Extending antibiotic use to all invasive procedures isn’t the most likely fix, they observe. “At least for those procedures where sterility should be easy to achieve and maintain, the solution is more likely to lay with improved sterile technique, infection control procedures, and identifying systematic approaches for reducing healthcare-associated bacteremia rather than necessarily advocating antibiotic prophylaxis.”

In terms of next steps, Jansky said “a randomized study or a similar observational study to ours but with data on microbiology and antibiotic use could be very interesting but especially the first would also be very challenging.”

  • Janszky I, Gémes K, Ahnve S, et al. Invasive procedures associated with the development of infective endocarditis. J Am Coll Cardiol. 2018;71:2744-2752.

  • Thornhill MH, Dayer MJ, Cahill TJ. Infective endocarditis after invasive medical and surgical procedures. J Am Coll Cardiol. 2018;71:2753-2755.

  • The study was funded by grants from the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology and from the Swedish Research Council.
  • Jansky and Thornhill report no relevant conflicts of interest.