Abstract
Background
Fungal infective endocarditis (IE) is rare but potentially fatal. Heart transplantation (HT) may be considered in selected patients when conventional therapy fails, but indications remain unclear.
Case Summary
A 44-year-old man developed acute heart failure due to Streptococcus agalactiae native valve IE with severe aortic regurgitation, requiring emergent aortic valve replacement. Early prosthetic valve IE due to Candida tropicalis occurred, complicated by recurrent periprosthetic pseudoaneurysms. Extracardiac infection was excluded. HT was successfully performed. No episodes of rejection or recurrence of IE occurred after 2 years of follow-up.
Discussion
Although there is little literature on the subject, some cases of HT as salvage treatment for inoperable IE have been reported. HT should be considered an exceptional strategy for highly selected patients. Multidisciplinary decision-making is crucial.
Take-Home Message
In selected patients with inoperable IE, HT may be a therapeutic option, but it should be framed as an exceptional, last-resort intervention.
Key words: acute heart failure, cardiac transplant, endocarditis, valve replacement
Graphical Abstract
History of Presentation
A 44-year-old man presented with fever and chills of a month's duration, associated with dyspnea and abdominal pain. He denied any other accompanying symptoms. Upon admission, his blood pressure was 140/63 mm Hg, heart rate was 110 beats/min, oxygen saturation was 94% on room air, and body temperature was 38.8 °C. He was in fair general condition and presented a diastolic murmur at the aortic focus, jugular vein distention, signs of pulmonary congestion, and pitting edema in the lower extremities.
Take-Home Messages
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Heart transplantation may be a viable treatment option for highly selected patients with nonrepairable prosthetic infective endocarditis and recurrent perivalvular destruction.
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Multidisciplinary team involvement is essential for complex decision-making.
Past Medical History
The patient did not report any significant medical history.
Differential Diagnosis
The patient's symptoms and physical examination findings quickly raised the suspicion of infective endocarditis (IE).
Investigations
At the time of consultation, an electrocardiogram showed sinus tachycardia with no other notable alterations. Signs of vascular redistribution were found on chest x-ray.
A blood test showed normal blood count, unaltered coagulation times, preserved renal function, and elevated levels of C-reactive protein (213 mg/L), procalcitonin (6.31 ng/mL), and high-sensitivity troponin (71 ng/L). Viral hepatitis, human immunodeficiency virus, and syphilis serologies were negative.
All 4 sets of blood cultures performed yielded positive results for Streptococcus agalactiae.
Abdominal ultrasound and computed tomography showed diffuse hepatic steatosis with no other abnormalities.
Transthoracic and transesophageal echocardiography (TTE, TEE) revealed a normal-sized left ventricle with hyperdynamic systolic function (ejection fraction: 76%) and normal right heart function, severe and acute aortic insufficiency on a likely bicuspid native valve, thickened leaflets with tissue loss, and moderate functional mitral regurgitation (Video 1).
Management
Supplementary oxygen, diuretics, and broad-spectrum antimicrobial therapy were initiated, later narrowed to ceftriaxone based on blood cultures. After 3 days of targeted antibiotherapy and negative control blood cultures, the patient developed rapid respiratory deterioration for which he underwent urgent aortic valve replacement with a 23-mm On-X mechanical prosthesis (Artivion), requiring vasoactive and inotropic support postoperatively. Culture of the native valve was positive for Streptococcus agalactiae.
During the first postoperative hours in the intensive care unit, the patient developed multiorgan failure with acute renal failure, ischemic colitis, and hepatitis. TTE showed severe ventricular dysfunction and ruled out cardiac tamponade. Central venoarterial extracorporeal membrane oxygenation (VA-ECMO) was initiated, leading to progressive hemodynamic improvement, and was removed after 5 days. During this period, transitory parenteral nutrition was required.
The patient was transferred to the cardiology ward and remained hemodynamically stable. On postoperative day 14, he developed fever, and new blood cultures were positive for Candida tropicalis. All vascular catheters were removed, and antifungal treatment with anidulafungin was added. Repeat TTE and TEE showed IE on the aortic mechanical prosthesis with a periprosthetic pseudoaneurysm causing moderate to severe leak, severe functional mitral regurgitation, and moderate biventricular dysfunction (Video 2). Cardiac computed tomography depicted a voluminous pseudoaneurysm dependent on the left ventricular outflow tract (Figure 1, Video 3). Blood cultures became negative after 10 days of antifungal therapy.
Figure 1.
Cardiac Computed Tomography Showing a Voluminous Pseudoaneurysm Dependent on the Left Ventricular Outflow Tract
(A) Axial and (B) oblique coronal views of the prosthetic aortic valve showing a perivalvular contrast-filled cavity that corresponds to a periprosthetic pseudoaneurysm (white arrows) extending/originating from the left ventricle outflow tract. (C) Volume rendering and (D) maximum-intensity projection images depicting the close relationship of the pseudoaneurysm to the left main coronary artery (black arrows).
After 32 days of anidulafungin, a second cardiac surgery was performed with mitral and aortic valve replacement using the 27-mm and 23-mm Bicarbon prostheses (Sorin Biomedica) and closure of the pseudoaneurysm with a pericardial patch. The culture of the mechanical prosthesis was positive for Candida tropicalis, and fluconazole was added to anidulafungin.
Postoperative evolution was initially satisfactory. However, a follow-up TEE 1 month later revealed a new large periprosthetic aortic pseudoaneurysm (Video 4), confirming ongoing local structural destruction.
Given repeated surgical failure, extensive perivalvular involvement, and no evidence of extracardiac infection, heart transplantation (HT) was considered the definitive curative therapy. Antifungal treatment was transitioned to oral isavuconazole, with careful monitoring of drug-drug interactions with planned immunosuppression. The patient was discharged home with heart failure therapy and isavuconazole. Follow-up visits were scheduled at the transplant center.
Four months after discharge, HT was successfully performed. Basiliximab was used for induction therapy. Cultures of the explanted valves were positive for Candida tropicalis, while post-transplant blood cultures were negative. Control echocardiography showed preserved biventricular function and no signs of pulmonary hypertension. The patient was discharged on triple immunosuppressive therapy (tacrolimus, mycophenolic acid, and low-dose prednisone) and oral isavuconazole.
Outcome and Follow-Up
During the first year after transplantation, protocol biopsies showed no evidence of evidence of cellular or humoral rejection. Isavuconazole was continued for 6 months post-transplant, covering the period of maximal immunosuppression. Control blood cultures were negative. Two years after HT, the patient remains free from rejection, recurrent IE, or heart failure admissions.
Discussion
IE is an uncommon disease with high mortality. The primary treatment approach involves antimicrobial therapy; however, a significant number of patients may require surgery.1 Data from the Euro-Endo registry, which analyzed 3,116 patients diagnosed with IE, revealed that 69.3% had a theoretical indication for cardiac surgery, yet the procedure was only performed in 51.2% of cases.2
Candida accounts for about 1% of all IE cases, frequently associated with prosthetic valves, immunocompromised states, and parenteral nutrition.3 Although the emergence of new antifungals with strong activity against biofilms allows for medical treatment in some selected cases of Candida, fungal IE is generally regarded as an indication for surgical valvular intervention.3,4
IE can exhibit a high rate of recurrence, particularly in cases where the etiology is fungal, where it can occur in up to 30% of cases.5 In situations where repeated surgery fails to eradicate persistent or recurrent prosthetic valve IE, clinical management becomes even more complex. Although active infections are generally a contraindication for organ transplantation, in selected patients in whom the extracardiac extension of the infection has been ruled out and cardiac involvement is deemed inoperable, HT may be an option.6
There are few studies regarding the indication of HT as treatment for IE, especially of a fungal cause. In 2015, Aymami et al7 reported a series of 6 patients who underwent HT as salvage treatment for Staphylococcus or Streptococcus IE with extensive perivalvular lesions and end-stage heart failure; all patients survived with no relapse after a median follow-up of 24.5 months. In 2016, a Brazilian group reported a case of Candida krusei IE debuting with cardiogenic shock refractory to medical therapy, in which the patient underwent successful HT after 4 weeks of antifungal therapy.6 Culture of the valve was negative. Treatment with anidulafungin was maintained for 6 more weeks after HT, with no evidence of relapse.6 In 2023, an international group published a series of 20 patients with IE and heart failure, periannular abscess, or prosthetic valve dehiscence who underwent HT.7 The main pathogens were Streptococcus, Staphylococcus, and Enterococcus. Seven patients died (35%), 4 of them during the first month after HT. Of the patients who were discharged from the hospital, 81% survived with a median post-HT follow-up of 35.5 months, with no relapse of IE.7
Despite these reported successful cases, the timing, indications, and patient selection criteria have not been clearly defined in recent guidelines. The 2023 European Society of Cardiology guidelines state that, in exceptional circumstances, HT has been used for carefully selected patients who lack other surgical options.1 In the specific case of Candida IE, neither the post-HT antifungal treatment nor its duration is well established. Therefore, the endocarditis team plays a crucial role in individualized complex decision-making for patients with IE.
Conclusions
In selected patients for whom repeated surgery has failed to eradicate persistent or recurrent prosthetic valve IE and extracardiac extension has been ruled out, HT may be a viable salvage option. Multidisciplinary decision-making is crucial, and HT should be framed as an exceptional, last-resort intervention rather than a routine therapeutic approach.
Funding Support and Author Disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
Appendix
Visual Summary.
| Time | Events |
|---|---|
| Day 1 | A 44-year-old man presented with fever, chills, and decompensated congestive biventricular HF signs requiring admission. Blood cultures were positive for Streptococcus agalactiae. TEE showed IE on a bicuspid aortic valve with severe insufficiency. Oxygen, diuretics, and antibiotherapy were started. |
| Day 4 | Patient underwent cardiac surgery with aortic valve replacement for a mechanical prosthesis owing to rapid respiratory deterioration. Culture of the valve was positive for Sagalactiae. |
| Day 5 | Patient developed multiorgan failure, and VA-ECMO was initiated. Parenteral nutrition was required. |
| Day 10 | Removal of VA-ECMO after hemodynamic improvement. |
| Day 19 | Presented a peak of fever. Blood cultures were positives for Candida tropicalis. Anidulafungin was started. |
| Day 20 | TTE and TEE showed IE on aortic mechanical prosthesis with periprosthetic pseudoaneurysm causing moderate to severe leak, severe functional MR, and biventricular dysfunction. CT confirmed voluminous pseudoaneurysm. |
| Day 47 | With negative blood cultures, second cardiac surgery was performed with mitral and aortic valve replacement. Culture of the mechanical prosthesis was positive for Ctropicalis. |
| Day 90 | Follow-up TEE and CT showed a new large periprosthetic aortic pseudoaneurysm. The case was discussed with the endocarditis team, and the patient was referred to a transplant center. |
| Day 124 | After completing pretransplant study and in the absence of extracardiac septic focus, the patient was listed for HT and discharged home with HF therapy and isavuconazole. |
| Day 229 | HT was performed. |
| Day 253 | TTE with preserved biventricular function. First biopsy without evidence of rejection. Discharged home with tacrolimus, mycophenolic acid, low-dose prednisone, and oral isavuconazole. |
| Day 410 | Isavuconazole was discontinued after completing 6 months of post-transplant treatment. Control blood cultures were negatives. |
| Day 700 | No episodes of rejection and no admissions for HF 2 years after HT. |
Appendix
Transesophageal Echocardiography Showing Severe Aortic Insufficiency on a Likely Bicuspid Native Valve and Thickened Leaflets With Tissue Loss
Transthoracic and Transesophageal Echocardiography Showing Infective Endocarditis on the Aortic Mechanical Prosthesis, With a Periprosthetic Pseudoaneurysm Causing Moderate to Severe Leak
Cardiac Computed Tomography Cine Images Depicting the Great Pulsatility of the Periprosthetic Aortic Pseudoaneurysm
Note the close relationship with the left main coronary artery, which moves with the pulsatility of the pseudoaneurysm.
Follow-Up Transesophageal Echocardiography Showing a New Large Periprosthetic Aortic Pseudoaneurysm, With Ongoing Local Structural Destruction
References
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Associated Data
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Supplementary Materials
Transesophageal Echocardiography Showing Severe Aortic Insufficiency on a Likely Bicuspid Native Valve and Thickened Leaflets With Tissue Loss
Transthoracic and Transesophageal Echocardiography Showing Infective Endocarditis on the Aortic Mechanical Prosthesis, With a Periprosthetic Pseudoaneurysm Causing Moderate to Severe Leak
Cardiac Computed Tomography Cine Images Depicting the Great Pulsatility of the Periprosthetic Aortic Pseudoaneurysm
Note the close relationship with the left main coronary artery, which moves with the pulsatility of the pseudoaneurysm.
Follow-Up Transesophageal Echocardiography Showing a New Large Periprosthetic Aortic Pseudoaneurysm, With Ongoing Local Structural Destruction