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Challenging ‘dogma’ of allografts in infectious endocarditis

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Two commentaries: ‘Reasonable’ conclusions, but questions remain

The study by Dr. Kim and his colleagues joins a series of reports questioning conventional thinking on the use of homografts to prevent recurrent infective endocarditis (IE), but their propensity matching does not account for surgeon bias in selecting a prosthesis, Dr. James K. Kirklin of the University of Alabama at Birmingham said in his invited commentary (J Thorac. Cardiovasc Surg. 2016 May;151:1230-1).

For example, surgeon preference may account for the wide disparity in full root replacements, depending on the type of prosthesis, Dr. Kirklin said. “Some experienced homograft surgeons have preferred the intra-aortic cylinder technique or infracoronary implantation, which avoids the short-term and longer-term complexities of full root replacement and has demonstrated long-term structural durability equivalent to that of the full root replacement,” he said.

Also, experienced homograft surgeons may prefer the homograft for its resistance to infection and adaptability to severe root infection in individual patients, particularly in those with severe infection with an abscess. And he cautioned against the study’s implication that conventional prostheses are equivocal in the setting of IE.

“Of considerable importance, however, is the evidence-based conclusion that surgical referral of routine surgical aortic valve endocarditis to a center experienced with aortic homograft surgery is not necessary, and a justifiable expectation is that aortic valve endocarditis requiring operation can be safely and appropriately managed in centers with standard aortic valve surgery experience who do not have access to or experience with aortic valve homografts,” Dr. Kirklin concluded.

Dr. Kirklin had no financial relationships to disclose.

Dr. Christopher M. Feindel

The series by Dr. Kim and his colleagues, one of the largest of acute infective endocarditis to date, provides further evidence that the type of prosthesis used in surgery for IE involving the aortic valve probably does not affect long-term outcomes or reinfection rates, Dr. Christopher M. Feindel of the University of Toronto said in his invited commentary (J Thorac Cardiovasc Surg. 2016 May;151:1249-50).

However, Dr. Feindel said, “numerous confounding factors” inherent in any observational study could raise questions about the conclusion.

“This article delivers an important message, although not all surgeons will agree with the statistical approach taken by Dr. Kim and his colleagues,” Dr. Feindel said. The propensity scoring method the study used lacked all baseline variables that affect treatment choice and outcomes, “a crucial assumption for effective use of the propensity score,” he said. However, given the multitude of variables in patients with acute and complex IE, he said most surgeons would be hard pressed to accept that’s even possible in the model the study used.

Dr. Feindel also said a close examination of the 115 patients who underwent root replacement would have been “very instructional,” and the lack of follow-up on valve-related complications in almost 25% of the patients is another limitation of the study.

Nonetheless, the conclusions of Dr. Kim and his colleagues are “reasonable,” Dr. Feindel said. “Clearly, this article contributes important additional information to the surgical management of IE that will help guide surgeons, especially when it comes to prosthesis of choice,” he concluded. “It is up to the reader to decide whether this report finally puts to rest the “dogma” that homografts should preferentially be used in the setting of IE.”

Dr. Feindel had no relationships to disclose.


 

FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY

References

When a patient undergoes aortic valve replacement for infective endocarditis, conventional thinking holds that cardiac surgeons should use homografts because they have greater resistance to infection, but a recent study of more than 300 cases at two academic medical centers concluded that homografts may not necessarily offer such a benefit.

The study, published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:1239-48), involved 304 consecutive adult patients on whom 30-40 different surgeons performed operations for active infective endocarditis (IE) in the aortic valve from 2002 to 2014.

Under a very high magnification of 50,000x, this scanning electron micrograph shows a strain of Staphylococcus aureus bacteria taken from a vancomycin intermediate resistant culture. ©CDC/Janice Haney Carr

Under a very high magnification of 50,000x, this scanning electron micrograph shows a strain of Staphylococcus aureus bacteria taken from a vancomycin intermediate resistant culture.

“Our findings suggest that patient-specific factors, such as age and implant preference, as well as technical reconstructive considerations, should drive prosthetic choice, rather than surgical dogma,” said Joon Bum Kim, Ph.D., of Massachusetts General Hospital, Harvard Medical School, both in Boston, and Asan Medical Center in Seoul, Korea, and his colleagues.

The study found that cardiac surgeons favored homografts over conventional prostheses when the patient had prosthetic valve endocarditis (58.1% vs. 28.8%) and methicillin-resistant Staphylococcus aureus (25.6% vs. 12.1%), both significant differences.

“No significant benefit to the use of homografts was demonstrable with regard to resistance to reinfection in the setting of IE,” Dr. Kim and his colleagues said.

Because reinfection after valve replacement for IE is such a strong concern, the debate over which prosthesis is best has ensued for decades. The researchers pointed out that the evidence favoring autologous or allogeneic tissue over synthetic material in the infective field is weak, mostly built on single-armed observational studies without comparison to conventional prosthesis.

With that in mind, the researchers pooled data from two institutions to compare short- and long-term results for homograft vs. conventional prosthetic valves in patients with IE. In this study group, 86 (28.3%) had homografts, 139 (45.7%) had xenograft prostheses, and 79 (26%) mechanical prostheses. The homograft group had more than twice the rate of early death than did the conventional group – 19.8% vs. 9.2%, a significant difference (P = .019).

During follow-up, which ranged from 4.7 to 72.6 months, 60 patients (19.7%) of the total group died and 23 (7.7%) experienced reinfection, but rates did not vary between the homograft and conventional prosthesis groups, Dr. Kim and his colleagues reported.

Demographics were similar between the three groups with a few exceptions Those who received the mechanical prostheses were younger (mean age, 47.2 years vs. 55.6 and 59.8 for the homograft and xenograft groups, respectively), had lower rates of diabetes (5.1% vs. 10.5% and 12.2%) and had less-severe disease based on New York Heart Association functional class III or IV scores (34.2% vs. 54.7% and 53.2%). The types of IE pathogens also differed among the three groups; methicillin-resistant staphylococci was most common in the homograft group (25.6%), whereas the viridans group streptococci was the leading cause of IE in the mechanical (38% ) and xenograft groups (25.2% ).

The use of homografts involves a highly complex operation, typically requiring a complete aortic root replacement, which “may be the major drawback in recommending it to patients already at high risk of operative mortality,” the investigators wrote. The durability of homografts makes their use limited for younger patients, and such grafts are somewhat scarce and require cryopreservation. “Therefore, the notion that homografts are required may in practice present an obstacle to appropriate surgical management of patients who have IE,” Dr. Kim and his coauthors wrote. All patients but one in the homograft group received aortic arch replacement (98.8%) whereas 30 of the patients in the conventional group did so (13.8%).

The study findings are consistent with an earlier comparative study (Ann. Thorac. Surg. 2012;93:480-07), according to Dr. Kim and his colleagues. “These findings suggest that patient-specific factors, such as patient preferences and technical considerations, should be the principal drivers of choices of valve prostheses,” they said. “Furthermore, lack of access to homografts should not be considered an obstacle to surgical therapy for this serious condition.”

Coauthor Dr. Sundt disclosed that he is a consultant for Thrasos Therapeutics. Dr. Kim and the other coauthors had no financial disclosures.

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