Future directions in infective endocarditis

Introduction

The first descriptions of endocarditis appeared in the literature in the 1600s at a time when the anatomy and physiology of the heart was still incompletely characterized [ ]. Since that time, significant progress in medicine, including advances in imaging techniques, antimicrobial therapy, and surgical interventions, have ushered in a new era of management of patients with infective endocarditis (IE). This disease that once perplexed notable figures in the history of medicine, including Giovanni Morgagni and Rudolf Virchow, continues to challenge clinicians in the current era, though undoubtedly outcomes have significantly improved [ , ]. In the following sections, we will outline current trends in IE that offer opportunities and challenges for diagnosis and management in the future. Additionally, we will highlight areas of continued work in an effort to better understand this complex disease process.

Trends in intravenous drug use

The opioid epidemic is an alarming trend and has been deemed a national public health crisis in the United States [ , ]. Consistent increases in abuse of prescription opiates as well as disturbing trends in the use of heroin and fentanyl have been observed over the past decade [ ]. The incidence of heroin-associated drug overdose deaths increased from 0.7 per 100,000 to 4.9 per 100,000 between 1999 and 2017, though more recent rates appear to have equilibrated [ ]. As anticipated, rates of intravenous drug use (IVDU)-associated IE have increased in parallel which has shifted the epidemiology of IE [ , ]. Patients with IVDU-associated IE are more likely to have right-sided IE, often have more virulent organisms, and may have complicated long-term clinical courses due to continued drug use [ ]. Practices including needle sharing, licking of needles, lack of skin cleaning prior to injection, and contaminants in the drug mixture may all contribute to bacteremia and increase the risk of IE. Thus, efforts such as needle exchange programs and treatment with opioid agonists, both of which aim to curb the spread of communicable diseases, may potentially have beneficial effects in reducing the risk of IE [ ].

Nevertheless, it is difficult to project future trends in IVDU and thus its impact on the future of IE remains unclear. What is certain, however, is that this public health crisis is not disappearing. Use of synthetic opioids such as fentanyl has risen precipitously since 2013 and furthermore, patients who abuse prescription opioids, such as oxycodone, are 19 times more likely to use heroin [ , ]. In the United States, a multifaceted approach to address the crisis has been outlined which targets addiction and treatment services as well as research to better quantify the burden of the disease and to develop innovative strategies for addiction treatment and opioid-free pain management. It remains to be seen what impact these public health measures will have on persons currently using intravenous drugs as well as on the distribution of prescription opioids, which is a critical factor given the potential for progression to IVDU. Both of these aspects will determine the future profile of IE patients.

These trends also underscore the valuable role of Addiction Medicine in the long-term management of patients with IVDU-associated IE. This patient population displays high rates of readmission and recurrent IE attributable to continued IVDU and furthermore, the predominant cause of death among patients with IVDU-associated IE is recidivism [ , ]. Additionally, reoperative valve surgery is associated with a significant increase in 30-day mortality when compared to patients undergoing an initial surgery for IE [ ]. At present, attempts to curb continued IVDU have fallen short yet this represents a critical component of long-term IE management that also stands to lessen healthcare costs [ ]. Involvement of Addiction Medicine specialists in the care of these patients has been associated with reduced readmissions [ ]. A multidisciplinary approach will be necessary to ensure abstinence from IVDU and thereby address the risks of recurrent IE in this patient population. This will need to be integrated into outpatient follow-up for patients with IVDU-associated IE following the initial hospitalization.

Risk stratification

IE occurs in only a minority of patients with a prosthetic valve or with predisposing conditions, thus prediction of patient populations at highest risk of IE is critical for determining prophylactic therapy and directing work-up. Various models have been proposed to not only estimate the risk of IE but also to predict the ultimate need for surgery as well as long-term outcomes following medical or surgical management. Leveraging large cohorts, these tools offer the promise of guiding patient expectations as well as guiding optimal management strategies.

First and foremost, many studies have focused on the risk of IE in patients with prosthetic valves undergoing high-risk procedures in order to guide antibiotic prophylaxis. The most current guidelines for the prevention of IE from the American Heart Association (AHA) date back to 2007 and specify both high-risk patient populations and prophylaxis recommendations for based on various procedure types [ ]. The authors acknowledged the difficulty in ascertaining well-supported data to guide their recommendations, given the low overall incidence of IE, and called for randomized trials comparing antibiotics to placebo to conclusively define the relative risks and benefits in various groups [ ]. Though dental procedures may incite a transient bacteremia, the association between this and the development of IE is still unclear and the overall lack of evidence has led to disparate guidelines with the AHA recommending antibiotics to only high-risk groups whereas in the United Kingdom no antibiotic prophylaxis is recommended [ ]. Large population studies with longitudinal follow-up and detailed data regarding the type of invasive procedure as well as the quantity and timing of any prophylactic antibiotic administration will be necessary. From a cost-effectiveness perspective, one study has suggested that antibiotic prophylaxis may be beneficial in high-risk patients; thus, cost effectiveness along with clinical outcomes should be incorporated into future published guidelines [ ].

Studies have also focused on estimation of postsurgical mortality in order to predict outcomes following repair. Contributors to mortality among patients with IE include older age, prosthetic valve-associated infections, the causative organism, and systemic manifestations [ ]. The EndoSCORE, for example, was developed specifically to predict postoperative mortality and factors in age, sex, comorbidities, the presence of a perivalvular abscess, preoperative cardiac and renal function, and the infectious species [ ]. The majority of these studies are derived from retrospective review of existing databases, many of which do not contain granular data specific to IE treatment, including the causative microorganism and exact details of more complex operations, which may be required in cases of perivalvular involvement. This is one important limitation of the use of databases such as the Society of Thoracic Surgeons (STS) database. More complex analyses with the incorporation of prospective data collected for the purposes of risk stratification for IE would help to refine estimation of patient outcomes under different treatment scenarios. Additionally, application of validated risk scores to the prospective risk stratification of patients presenting with IE and multiple risk factors for poor outcomes may provide objective guidance to suggest how to best manage these patients.