Gerbode defect resulting from ineffective treatment of infective endocarditis: a case report

Abstract

Background

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Infective endocarditis is a common medical complication in patients with intravenous drug use (IVDU). staphylococcal infection is the predominant pathogen in left-sided endocarditis. Cardiac abscesses are more common in prosthetic valves. Should they rupture, they often create fistulous tracts in addition to prosthetic valve dehiscence, conduction abnormalities, and acute coronary syndrome.

Case presentation

A 51-year-old man with history of IV drug use, methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis, and bovine aortic valve replacement was treated for MSSA bacteremia and was discharged on dalbavancin. The transesophageal echocardiogram (TEE) was negative for abscess or vegetation. Three days later, he presented with fever, worsening mental status, and neurologic deficits with infarcts in the brain, lungs, spleen on imaging. TEE was negative for vegetation or abscess. After transfer to a quaternary care center four days later, TEE showed a large aortic root abscess that eroded the membranous ventricular septum resulting in a Gerbode defect. Then, he sustained a non-shockable rhythm cardiac arrest. The patient was transferred to the cardiac ICU where emergent TEE showed complete dehiscence of the septum and a loosely attached prosthetic aortic valve. After a second cardiac arrest and resuscitative efforts, the patient expired.

Conclusion

This case highlights that inadequately treated infective endocarditis can rapidly progress and cause serious complications. If patients with prosthetic valves develop bacteremia and have negative TEEs, retrospectively-gated CTs should be obtained to evaluate for perivalvular extensions. Currently, there have been no published studies demonstrating patients with infective endocarditis who were treated with Dalbavancin that progressed to fistulous tracts. Further research is required to investigate the effectiveness of long-acting lipoglycopeptides, such as Dalbavancin, in treating infective endocarditis. This case demonstrates a rare, but a serious medical emergency that can arise in patients with prosthetic heart valves and positive blood cultures when not detected early and treated promptly.

Background

Infective endocarditis is one of the most common medical complications in patients with intravenous drug use (IVDU). One in every 10 invasive staphylococcal infection can be attributed to IVDU, and it is the predominant pathogen in left-sided endocarditis [1]. Staphylococcal species have been linked to more rapid growth of vegetations, and the presence of larger vegetations carries a greater risk of embolization, valvular regurgitation, and cardiac failure [2]. Potential complications include systemic embolization, perivalvular extension and abscess formation [1]. Although cardiac abscesses are rare, they are more common with prosthetic valves. Should they rupture, they often create fistulous tracts in addition to prosthetic valve dehiscence, conduction abnormalities, and acute coronary syndrome. Here we present a case of rapidly progressive aortic root abscess after partially treated infective endocarditis.

Case presentation

A 51-year-old man with a history of former IV drug use and prior methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis with prior bovine aortic valve replacement presented to his local hospital and was diagnosed with MSSA bacteremia. The patient was treated over a 10-day period and subsequently discharged with plans for four weekly treatments of dalbavancin. The transesophageal echocardiogram (TEE) at the time was negative for abscess or vegetation (Fig. 1).

Fig. 1

TEE at Outside Hospital: Two-dimensional TEE, mid-esophageal, short-axis view, systolic phase, demonstrates an open aortic valve without vegetation or abscess (green arrow)

Three days after discharge from his local hospital, he re-presented there with fever, worsening mental status, and neurologic deficits. Imaging showed infarcts in the brain, lungs, spleen and possibly kidneys. Repeat blood cultures were positive for MSSA. It was reported that TEE at the time was negative for vegetation or abscess. He met Modified Duke Criteria for possible infective endocarditis with his positive blood cultures and evidence of embolic infarctions on imaging. The patient was transferred four days later to a high acuity, quaternary care center due to worsening clinical status. The TEE obtained on arrival showed a large echodensity within the right atrium with perivalvular extension of the infection in the aortic root that eroded the membranous ventricular septum into the right atrium resulting in a Gerbode defect (Fig. 2). Cardiovascular surgery and neurology were consulted on arrival. The consulting teams reviewed the patient’s presentation and images. Because of the acute strokes secondary to presumed septic emboli, the patient was not offered immediate surgery given the risk of hemorrhagic transformation with the intraoperative heparin required for bypass at the time of surgery.

Fig. 2

Two-dimensional TEE, mid-esophageal, 4-chamber view demonstrates a large, echodensity within the right atrium (yellow arrow) with perivalvular extension of the infection in the aortic root and erosion of the membranous septum into the right atrium also known as a Gerbode defect (green arrow). The vegetation is also in close proximity to the tricuspid valve (purple arrow). RA: right atrium, LA: left atrium, RV: right ventricle, LV: left ventricle

With Doppler, perivalvular extension of the aortic root infection and erosion of the membranous septum into the right atrium with continuous left-to-right flow between the left ventricle outflow tract and right atrium, along with severe aortic regurgitation with a large flow convergence zone (Video 1).

ECG at the time (ECG A) was largely unremarkable for conduction abnormalities other than one premature ventricular contraction (PVC). Given the high risk of progressive conduction disease in the setting of an aortic root abscess, ECGs were obtained daily.

ECG A: Normal axis, sinus tachycardia, rate 107 with a single PVC

ECG A: Normal axis, sinus tachycardia, rate 107 with a single PVC.

Additionally, the patient was monitored on telemetry. On the third day of admission, a new electrical disturbance was noted, thus ECG B was immediately obtained that showed a new first-degree AV block as well as right bundle branch block (ECG B). Because of the new electric conduction disease, there was a high degree of suspicion that their infection had progressed.

ECG B: Pre-arrest ECG with sinus rhythm with new 1 st degree AV block and new right bundle branch block, nonspecific ST and T wave abnormalities, and a prolonged QT interval.

In addition to the new electrical disturbance, the patient had progressive respiratory distress culminating in hypoxic respiratory failure requiring emergent intubation, during which they sustained a 6-minute cardiac arrest with a non-shockable rhythm before a perfusing rhythm was again obtained. The patient continued to require vasopressor and inotrope support. Limited transthoracic echo (TTE) (Video 1) showed rocking aortic valve and probable aortic regurgitation.

The patient was immediately transferred to the cardiac ICU where an emergent TEE was obtained and confirmed complete erosion of the interventricular septum and dehisced bioprosthetic aortic valve (Fig. 3, Video 3 & 4).

Fig. 3

Dual display image of cardiac cycle. Top: systole; Bottom: diastole. TEE, mid-esophageal 4-chamber view showing large vegetation in the right atrium (yellow arrow) and associated Gerbode defect (green arrow). (MV: mitral valve, TV: tricuspid valve, RA: right atrium, LA: left atrium, RV: right ventricle, LV: left ventricle)

Over the next hour, he continued to decline, culminating in a second cardiac arrest. Given patient’s former and acute neurologic deficits secondary to cardioembolic strokes, further medical therapies and resuscitative efforts were deemed incompatible with a high quality of life. The patient subsequently expired.

Discussion

The time course to infective endocarditis (IE) has gotten more acute as patients are presenting earlier and without the classical findings. This is due to the changing patient population at risk for infective endocarditis, that includes those with degenerative valve disease, prosthetic valves, health-care related exposures, and injection drug use. IE complications comprise stroke, embolization other than stroke, heart failure, and intracardiac abscesses [3]. Intracardiac abscesses can further progress to fistulous tracts such as the Gerbode defect [4].

The Gerbode defect is an uncommon fistulous tract between the left ventricle and right atrium. Frank Gerbode was the first surgeon to successfully correct congenital left ventricular to right atrial shunting in 1958 [5]. It is primarily classified as a congenital defect, however recently the incidence of acquired defects are rising due to the increased occurrence of invasive cardiac procedures and infective endocarditis [6]. One center catalogued the outcomes of all their patients with a Gerbode defect over 20 years [7]. The majority of the defects were acquired (88%). In regard to management, half of the cases were managed conservatively, and the other half were managed with surgical or percutaneous repairs. Mortality within 30 days was higher in those patients managed non-operatively as compared to surgically [7]. This trend continued when looking at 1-year and 5-year survival rates as well. At a median follow-up of 3 years, about a quarter of the patients had died, another quarter suffered complications including heart failure hospitalizations, strokes and IE, yet half of the patients survived without major complications [7].

Class I recommendations state that TEE should be performed in cases where TTE is negative and repeated in three to five days if initial TEE is negative in patients with high clinical suspicion of infective endocarditis. In prosthetic valve patients, especially, TEE may miss early abscesses or paravalvular complications due to acoustic shadowing. However, with the increase in multimodal imaging modalities, guidelines have yet to define their role in IE [1]. Cardiac CT can play a complementary role to echocardiography in IE, especially in patients with suboptimal echocardiography results due to prosthetic valves or calcifications [8]. The European Society of Cardiology has incorporated Cardiac CT into their modified diagnostic criteria for IE [9]. Cardiac CT can be used to detect abscesses and pseudoaneurysms with a similar diagnostic rate to TEE and can possibly detect perivalvular extension with greater frequency. Furthermore, in prosthetic valves, it may be equivalent or greater than echocardiography for identifying prosthesis-related complications [9]. The protocol to look at IE differs to the standardized protocol of Cardiac CTs, which is typically prospectively gated to further examine the coronary anatomy. Prosthetic heart valves can create significant artifacts when imaged with echocardiography, thus making cardiac abscesses challenging to visualize [8]. This case exhibits the importance of following a negative TEE with repeat imaging in patients with persistent fever, positive blood cultures, and embolic events including repeat echocardiography and retrospectively-gated Cardiac CT scans as clinical suspicion of IE overrides negative imaging.

Treatment of infective endocarditis typically consists of surgical intervention and intravenous antibiotic therapy. Between 1969 and 2000, the proportion of IE cases undergoing surgery increased by 7%. Currently, about 50% of IE patients undergo surgery [1]. The timing of surgical intervention when patients have suffered a cerebrovascular infarct is debated. The risk of embolus has been thought to be higher within 14 days of IE diagnosis. Moreover, the patients who underwent early surgery had a significantly lower in-hospital mortality than those patients receiving antibiotic therapy alone (3% vs. 24%, P <.001).¹⁰ Additionally, other reports have suggested that the 72-hour period after initial cerebral complication imparts a lower risk of secondary cerebral hemorrhage. One center compared clinical outcomes after surgical intervention in patients with severe stroke and non-severe stroke (NIHSS ≥ 11 and NIHSS ≤ 10 respectively) and found that early surgery in patients with non-severe stroke may be beneficial [10]. Based on the aforementioned studies [7, 10]the outcomes suggest that earlier surgical interventions in these patients result in greater survival rates.

In regard to antibiotic treatment, the principle goal is to sterilize infection, yet in IE, this goal can be highly dependent on the characteristics of the infected vegetations. These infections are typically extremely dense with a slow rate of bacterial growth and metabolism, prompting the need for prolonged, parenteral antibiotic treatment [11]. In our case, we highlight the ineffectiveness of Dalbavancin in a patient who had a clear surgical indication. Dalbavancin was found to be effective in curing patients with prosthetic endocarditis that underwent surgery in the DALBACEN cohort [12]. Because Dalbavancin has not been well studied in prosthetic valve endocarditis, and in the small DALBACEN cohort, those with prosthetic valve endocarditis also underwent surgery along with treatment with Dalbavancin. We speculate that its use contributed to inadequate source control and that our patient would have had a better outcome with standard of care therapy since he was not offered surgery. Furthermore, Dalbavancin, it is not currently FDA-approved for use in IE [13]. The once weekly dosing of Dalbavancin makes it an attractive option for the treatment of deep infections, especially in populations where adherence is a concern. Upon further examination of the review’s data, the infective endocarditis data included 19 patients, and only seven patients had S. Aureus as the pathogen [12]. This review attempted to control for the use of dalbavancin by selecting patients whom received other antibiotics less than 14 days [12]whereas in other retrospective reviews that propone the efficacy of Dalbavancin in IE, the patients received a median duration of antibiotics of 28 days prior to transition to dalbavancin [13].

Although development of a Gerbode defect is rare, reports of it have increased in the past few years [7, 14]. ​Gerbode defects can be diagnostically challenging. This case underscores that in IE, clinical features, rather than imaging alone, must drive the diagnostic process in patients with embolic events, bacteremia and even new regurgitation as in a recently published case report in JACC [15]. Although vegetations are pathognomonic for IE, the lack of vegetations does not rule out the disease. Thus, patients with significant risk factors for infective endocarditis including history of infective endocarditis and prosthetic heart valves need a high index of suspicion when evaluating for infective endocarditis and their ensuing complications.

Conclusion

The incidence of fistulous tracts such as the Gerbode defect is rising due to the increased incidence of prosthetic heart valves. Thus, our index of suspicion for IE and its complications, especially in those with prosthetic heart valves, for this urgent complication must rise as well. When TEEs are negative in patients with prosthetic heart valves and bacteremia, retrospectively-gated cardiac CTs should be considered to look for perivalvular extension or vegetations that may have not been apparent on echocardiography. This case demonstrates a rare, but a serious medical emergency that can arise in patients with prosthetic heart valves and positive blood cultures when not detected early and treated promptly.