Infective endocarditis is more common and is poorly treated with conservative internal medicine. Once diagnosed, surgery should be actively considered if drug therapy is not effective and can often save the patient’s life. Subacute infective endocarditis is more common than acute infective endocarditis and often has poor outcomes due to the long duration of the disease, poor systemic condition, and the use of many types of antimicrobials to bacterial resistance.
Infective endocarditis is mostly caused by bacteria, commonly Streptococcus gramineus, Streptococcus hemolyticus, Staphylococcus aureus, Gram-negative bacilli, and to a lesser extent, fungi. Infective endocarditis can be divided into two categories, namely primary infective endocarditis and secondary infective endocarditis. Primary endocarditis refers to infection of the endocardium or valves via the bloodstream route due to various foci or routes of infection, such as long-term intravenous drug use in drug-addicted patients. Secondary endocarditis refers to infective endocarditis secondary to heart disease, post-valve replacement, pacemaker placement, long-term placement in a central vein, or after other cardiac surgery.
Patients with congenital heart disease, valve disease, or who have undergone heart surgery are susceptible to this disease. In the United States, the incidence of infective endocarditis is approximately 1.7-6.2 patients per 100,000 person-years. The American College of Cardiology reports that about 15,000-20,000 people develop infective endocarditis each year. In our country, the incidence of this disease is not well defined. The disease is more common in males, with a male to female incidence ratio of about 2:1.
[Clinical manifestations
The clinical manifestations of infective endocarditis are a combination of local damage to the heart and the immune response of the body.
1. Systemic infection
Fever is the most common symptom in patients with SBE. The duration of fever varies, and individual cases continue to have intermittent fever for as long as 10 years. The fever pattern is irregular, mostly seen in the chills fever type, sometimes only low fever. Patients complain of generalized aches and pains, fatigue, weight loss, pallor, and anemia. In long-standing cases, splenomegaly, pestle finger and hematuria may be present, and abscesses of important body organs may develop. The number of cases of typical infective endocarditis has decreased. Patients who have persistent temperature after direct intracardiac surgery for 1 week with the application of antibiotics, or who have high fever again after normal temperature, should have high suspicion of secondary SBE and need close observation and treatment, and relevant investigations.
2.Heart performance
Most of the patients can hear heart murmur, or new murmur based on the original heart murmur, or the nature of the original heart murmur changes. Changes in heart murmurs are characteristic of infective endocarditis. Patients with infective endocarditis may also have no heart murmur. The presence of a heart murmur is accompanied by hemodynamic instability or even deterioration, with patients presenting with intractable heart failure (90%), mostly due to severe aortic or mitral valve insufficiency, or due to infection that destroys intracardiac structures and causes shunting within the heart chambers. If the aortic infection extends to the adjacent heart chambers, arrhythmias may occur in some cases, with conduction block being more common, often suggesting that the infection extends to the conduction system.
3.Embolism
Embolism can occur in both body circulation and pulmonary circulation, but embolism in body circulation is more common. It can occur at any stage of the disease, and some cases even start with embolism. Embolism can lead to multiple organ damage, and the clinical manifestations vary depending on the involved organs. Cerebral embolism: often occurs in the middle cerebral artery and manifests as hemiparesis and aphasia. Cerebral hemorrhage: A blood vessel in the brain ruptures due to a bacterial aneurysm, causing hemorrhage, or it can be a coexistence of embolism and hemorrhage. Renal embolism: presents with back pain, and hematuria. Splenic embolism: can present with severe pain in the left upper abdomen. Coronary embolism: It can cause acute myocardial infarction. Mesenteric artery embolism: presents with acute abdominal pain and manifestations of intestinal obstruction. Arterial embolism of the extremities: pain in the distal end of the embolized limb, chills, and diminished or absent arterial pulsation. In addition, there may be oval hemorrhage on the retina, i.e. Roth spots. Skin bruises are common, mostly in the trunk, and may be caused by increased capillary fragility, ruptured hemorrhage or microembolism. Painless bruises on the skin of the palms and soles of the feet are called Janeway nodes. A total of 311 cases were treated surgically between 1990 and 2001 at Fu Wai Cardiovascular Hospital, including 65 cases of congenital heart disease and 246 cases of valvular disease (mitral, aortic, and tricuspid valves), including 51 cases of aortic valve combined with mitral valve lesions, 109 cases of simple aortic valve lesions, 80 cases of mitral valve lesions, and 6 cases of tricuspid valve lesions. Arterial embolism occurred in 16 cases (8%), and the patients presented with cerebral embolism and limb artery embolism. Infective endocarditis secondary to cardiac surgery is mostly caused by mycobacteria and may be related to unfavorable postoperative recovery, poor organism resistance and improper application of antibiotics in patients.
4. Immune system damage
Immune complex formation and deposition in the glomerular basement membrane can cause glomerulonephritis, and patients show hematuria, proteinuria and abnormal renal function. In addition, immune complexes deposited in the palm of the hand or plantar skin can form Osler nodules or Janeway nodules, which should be given sufficient attention.
Ancillary tests
1.Laboratory tests
(1) Blood culture
Patients with infective endocarditis may have persistent bacteremia. However, due to the widespread use of antibiotics, the positive rate of bacterial culture is not high. For suspected cases, culture should be performed at least 3 times within 24h for 3 consecutive days before positive results may be obtained. The distribution of bacteria is random, each blood collection should take 10ml of venous blood from different parts, and do aerobic and anaerobic bacteria culture respectively, no bacterial growth should also be cultured for more than 3 weeks. If the culture is positive, drug sensitivity test should be done to guide the treatment. Blood culture is best performed before the application of antibiotics. For those who have applied antibiotics, if the condition allows, the blood culture can be done after 3 days of discontinuation. The best time to draw blood is when the patient has chills, and if necessary, arterial blood culture or bone marrow culture is taken. Bacteremia is not always accompanied by chills and hyperthermia, so multiple blood cultures are needed to clarify the diagnosis.
For those with multiple negative blood cultures and long-term application of a large number of broad-spectrum antibiotics, fungal infections should be highly guarded and fungal tests can be done if necessary. Blood culture is an important laboratory test in the treatment of infective endocarditis. A positive blood culture can not only establish the diagnosis, but also guide the effective application of antibiotics, and thus blood culture tests should be emphasized during the treatment process. However, because the clinical rate of positive blood culture is not high (36.7%), complete reliance on blood culture results may delay the disease.
(2) Blood routine
Patients mostly have anemia, and the white blood cell count may increase, mostly accompanied by neutrophilia. In young and middle-aged patients, blood routine can be used to assess the development of the disease or as an indicator of improvement after treatment; in elderly patients or extremely frail patients with low body response, blood routine cannot be used to assess the development of the disease.
(3) Routine urine and renal function tests
Patients with glomerular immune complex deposition, resulting in diffuse glomerulonephritis, may have proteinuria or hematuria, accompanied by abnormal renal function.
2.Electrocardiogram
ECG examination is mostly non-specific, or presents abnormal ECG caused by the original underlying cardiac disorder. However, patients with infective endocarditis still require frequent ECG examinations, and the presence of myocardial infarction or conduction disturbances often indicates a poor prognosis. Newly developed conduction disturbances indicate infection involving the conduction bundle or abscess formation at the aortic root, requiring urgent surgical treatment.
3.Chest x-ray
It is also a non-specific examination. However, in patients with cardiac insufficiency, a series of chest radiographs can be used to assess the patient’s cardiac function and response to anti-heart failure treatment based on the size of the heart and the degree of pulmonary stasis, as well as the diagnosis and evaluation of pulmonary infection, which can be helpful in selecting the timing of surgery.
4.Echocardiography
Echocardiography is important in the diagnosis and treatment of infective endocarditis. The diagnostic rate of endocarditis with two-dimensional ultrasound and esophageal ultrasound can reach 80% to 90%. Echocardiography can detect redundant organisms (90% to 100% detection rate), the presence of myocardial or periaortic valve abscess formation, the extent of valve damage, hemodynamic changes caused by endocarditis, and the detection of underlying lesions, which can be of guidance for prognosis and surgical indications and timing of surgery. Since the treatment of infective endocarditis takes a long time and the condition changes rapidly, repeated examinations should be performed several times.
[Diagnosis
The possibility of infective endocarditis should be highly suspected in cardiac patients with unexplained fever for more than 1 week, the presence of heart murmurs or changes in the nature of the original murmur, an increase in total leukocyte count, or a sudden increase in heart failure with intractable heart failure. If the patient is accompanied by embolic manifestations, the diagnosis is essentially clinically confirmed. A positive blood culture is of diagnostic value and provides a basis for the selection of appropriate antibiotics, but a negative blood culture does not exclude the diagnosis. Echocardiography often reveals superfluities, but the absence of superfluities does not exclude the diagnosis of infective endocarditis.
The diagnosis of infective endocarditis secondary to direct endocardial surgery is more difficult than that of primary cases, and is usually manifested by a temperature that does not subside for 1 week after direct endocardial surgery with antibiotics, or by a high fever after a normal temperature, and if a new heart murmur appears at the same time, or if there are signs of embolism in the body circulation, infective endocarditis should be highly suspected. If only fever is present, blood cultures can be repeatedly performed and a positive blood culture can confirm the diagnosis. A negative blood culture can be combined with an echocardiogram. In post-valve replacement patients, the presence of perivalvular leaks or perivalvular abscesses, abnormal prosthetic valve function, and the presence of intracardiac redundancy should be understood, and if redundancy is found, it can be used as a reliable basis for diagnosis. Echocardiography is more reliable for biological valves, while echocardiography is often difficult to accurately detect small redundancies in mechanical valves because of the strong echogenicity of the metal. Transesophageal echocardiography provides better images. Therefore, patients with persistent postoperative fever and suspected infective endocarditis should not just wait for blood culture or echocardiography results, but should make a definitive diagnosis based on the patient’s cardiac function and a combination of clinical manifestations and various examination data.
[Treatment
Surgical treatment
(1) Timing and indications for surgery: Heart failure is the main cause of death in patients with infective endocarditis and is also the most important indication for surgery. Heart failure depends on the degree of valve involvement or damage from other lesions. Surgery should be actively considered when medical anti-infective therapy is ineffective or when heart failure cannot be controlled. Surgery during the period when the infection is not effectively controlled may lead to re-infection after surgery, but the continued development of heart failure will directly threaten the patient’s life, so choosing the appropriate time for surgical intervention is likely to ensure the patient’s life. Avoiding postoperative infection as much as possible is the basic principle of surgical treatment. The timing of surgery should not be delayed by one-sided emphasis on preoperative anti-infection treatment, because sometimes only surgical treatment can cure the disease. Continued conservative treatment may result in loss of patient’s life. Aggressive surgical treatment should be performed when the following conditions occur: ①Echocardiography reveals a superfluous organism, and it is clear that the valve is perforated or the superfluous organism is causing valve stenosis or incomplete closure. (ii) body circulation embolism caused by a redundant organism in the left heart system or pulmonary embolism caused by a redundant organism in the right heart. (③) Periaortic valve abscess formation with development of atrioventricular block. ④Aortic involvement with pseudoaneurysm. ⑤ Infective endocarditis secondary to valve replacement with severe infection that is not easily controlled by drugs, causing prosthetic valve dysfunction or perivalvular leakage or perivalvular abscess. (6) Infections caused by drug-resistant bacteria or fungi, but with poor prognosis if the infection is still present after surgery. (7) SBE can occur in precordial diseases such as ventricular defect, tetralogy of Fallot, and pulmonary stenosis, and should be treated by active surgery.
(2) Preoperative preparation: As with other cardiac surgery, intraoperative preparation is required to do bacterial culture of blood and tissues such as superfluous organisms in order to select appropriate antibiotics.
(3) Surgical approach: The purpose of surgery for infective endocarditis is to completely remove all infected or necrotic tissue, remove the redundant organisms and the tissue attached to them, and incise the abscess; repair or replace the damaged valve to restore valve function and correct other lesions or infectious complications of the heart. The key to surgery for infective endocarditis is that all infected tissue must be completely removed and the intracardiac lesion repaired. Surgical approaches include two main types of valve plication after lesion removal and valve replacement after lesion removal. Depending on the valve and the specific circumstances of the damaged valve, the appropriate procedure is chosen.
Mitral valve lesions: mitral valvuloplasty should be performed whenever possible. The outcome of mitral valvuloplasty depends on the estimation of the morphologic and functional changes in the valve and the surgical approach taken. The anterior mitral leaflet defect can be repaired with autologous pericardium; for anterior mitral leaflet free edge defects, the posterior leaflet tendon can be transferred to the anterior leaflet; for posterior mitral leaflet defects, the leaflet can be trimmed and sutured directly, depending on the extent of the lesion, or repaired and shaped with autologous pericardium; if shaping is not possible, valve replacement remains the primary treatment for infective endocarditis. Mitral valve replacement is simple, reliable, and has better long-term outcomes than medical therapy.
Aortic valve lesions: After aortic valve infection with endocarditis, in addition to leaflet tissue damage, abscesses often form near the annulus, making it difficult to perform valvuloplasty and necessitating aortic valve replacement, commonly with perivalvular abscesses and supra-aortic abscesses. Perivalvular abscesses mostly damage the aortic annulus and anterior mitral leaflet; supra-aortic abscesses may protrude outward into the aortic wall, forming a pseudoaneurysm that is always at risk of aortic hemorrhage, and the aortic wall defect should be repaired after removal of infected tissue. The most serious is aortic root abscess, where the infection can involve the aortic valve leaflets, annulus and ascending aorta, and even the cardiac stent structure. The aortic root should be replaced with a cryopreserved homologous valved aorta or artificial valved external conduit after complete removal of the lesion, and then the right and left coronary arteries should be grafted. Surgery should avoid damage to the conduction bundle.
Tricuspid valve damage: endocarditis in the tricuspid region, with lesions mostly confined to the valve leaflets, should be pursued for valvuloplasty. In Western countries, tricuspid valve damage is often severe and requires tricuspid valve replacement due to right heart infections caused by drug use. Infection of the venous system or cardiac catheterization, placement of a pacemaker
Pacemaker placement can also lead to tricuspid valve infective endocarditis, and the appropriate procedure should be selected based on the condition.
Secondary endocarditis after cardiac surgery: For secondary endocarditis after cardiac surgery, reoperation of the open chest should be done with extra care, using a swing saw to open the sternum, and then freeing the pericardial adhesions with an electric knife. When aortic lesions are suspected, the possibility of infection of the ascending aortic incision should be considered. Therefore, the femoral artery skin should be routinely disinfected and extracorporeal circulation should be established via femoral artery cannulation if necessary to prevent accidents when reopening the chest or establishing extracorporeal circulation. Prosthetic valve endocarditis is a serious complication after valve replacement and is divided into early prosthetic valve endocarditis and late prosthetic valve endocarditis according to the time of occurrence. Early prosthetic valve endocarditis may be associated with lax intraoperative and postoperative asepsis; late prosthetic valve endocarditis is associated with dental and urogenital infections.
Pathological changes vary depending on the type of prosthetic valve selected. Biologic valve infections tend to involve the valve leaflets first and can result in leaflet tears and perforations. Mechanical flap infections tend to originate in the suture ring and can lead to perivalvular abscesses, causing annular ulceration and severe valve closure insufficiency. The infecting organisms are mostly fungal or gram-negative bacteria, which are prone to embolic symptoms, poor conservative treatment, and easy recurrence. Regardless of whether the valve is biologic or mechanical, valve replacement should be performed as soon as possible if there is a manifestation of infective endocarditis. Biologic and mechanical valves have a similar chance of infection after surgery, and it is generally accepted that homologous aortic valves have better resistance to infection, and the appropriate valve can be selected according to the patient’s condition.
Contamination during or after surgery for various congenital heart diseases may lead to bloodstream infection and endocarditis, especially after correction of complex cardiac malformations, patients with low resistance and long recovery time are prone to combined intracardiac infections, such as incisional infections caused by uncontrollable drugs, suture tearing, or the appearance of redundant organisms in the heart, abnormal traffic between the chambers, and cardiac insufficiency, which should be actively treated surgically.
[Postoperative treatment
Ventilator-assisted respiration, maintenance of stable blood pressure and circulation, water-electrolyte balance, cardiac diuretic therapy, especially monitoring body temperature, blood routine and signs of systemic infection to understand whether the infection is under control. Intermittent transfusion of fresh blood, gammaglobulin or albumin can be used to enhance body resistance and accelerate postoperative recovery.
Patients should continue antibiotic therapy, and appropriate antibiotics can be selected based on the results of intraoperative specimen culture and drug sensitivity tests. If the postoperative culture is positive or the infection extends to the annulus, the medication should be continued until 6 weeks; if the inflammation is chronic or the infection has healed, long-term antibiotics are not required. Skin and other infections and dental disease should be prevented during treatment.
[Surgical Complications].
Perivalvular leakage, septal recanalization, pulmonary infection, and renal failure may occur and may require reoperative treatment.
Surgical results
Internal application of antibiotics for infective endocarditis is less effective, with a mortality rate of 30%-50%, mainly because the infection cannot be controlled, leading to multi-organ failure. The mortality rate of surgical procedures is 5%-20%, and the effect of surgical treatment is significantly better than that of medical treatment. Differences in patient condition and diagnostic criteria, as well as incomplete follow-up information, make treatment outcomes vary widely.