Infective endocarditis

Question 1

What is the most common signalment for dogs with IE

Answer 1

medium to large breed dogs
> 15 kg
middle-aged to old (> 5 years in more than 75%)
male sex predisposition

This demographic is more susceptible to the disease.

Question 2

What percentage of university teaching hospital caseloads does infective endocarditis represent in cats?

Answer 2

< 0.01%.

This indicates that feline cases are exceedingly rare.

Question 3

What are some severe pathophysiologic sequelae to infective endocarditis?

Answer 3

• CHF
• Immune-mediated diseases (e.g., polyarthritis, glomerulonephritis)
• Thromboembolism (sterile or septic)
• Severe cardiac arrhythmias

These complications can arise from the disease’s progression.

Question 4

What is the inciting event in the formation of infective endocarditis (IE)?

Answer 4

Bacterial adherence to the disrupted endothelial surface of a cardiac valve

This process is often initiated by mechanical lesions or inflammatory diseases.

Question 5

What can promote bacterial seeding within the endothelium?

Answer 5

• Mechanical lesions (subaortic stenosis, cardiac catheterization procedure)
• inflammatory disease

Examples include subaortic stenosis and cardiac catheterization procedures.

Question 6

What extracellular components are exposed by damaged endothelium?

Answer 6

Extracellular matrix proteins, thromboplastin, and tissue factor

These components trigger coagulation.

Question 7

What mediates the primary attachment of bacteria to disrupted endothelium?

Answer 7

Fibrinogen binding

This is a critical step in the initial stages of infective endocarditis.

Question 8

What triggers endothelial cell internalization and local procoagulant and proinflammatory responses in infective endocarditis?

Answer 8

Subsequent fibronectin binding

This binding leads to proinflammatory and procoagulant responses.

Question 9

What role do integrins play in the context of infective endocarditis? What cells express integrins?

Answer 9

endothilial cells –> integrins –> bind bacteria and fibronectin to the extracellular matrix

Their expression is induced by inflammation.

Question 10

Which bacteria carry fibronectin-binding proteins and can trigger active internalization by host cells?

Answer 10

Staphylococcus aureus

This characteristic enhances their pathogenicity.

Question 11

What types of bacteria commonly cause infective endocarditis? What is their advantage?

Answer 11

Staphylococcus and Streptococcus spp.

–> express special receptors called “microbial surface components”–> recognize adhesive matrix molecules –> can adhere to damaged valves

–> can trigger tissue factor production
–> induce platelet aggregation

These organisms have high ability to adhere to damaged valves.

Question 12

When should antimicrobial prophylaxis be considered?

Answer 12

In high-risk patients undergoing surgical or dental procedures

Examples include patients with subaortic stenosis.

Question 13

What do platelets release in response to tissue factor production?

Answer 13

Bactericidal proteins

However, many bacteria causing IE are resistant to these proteins.

Question 14

What can happen to bacteria such as S. aureus and Bartonella spp. during infective endocarditis?

Answer 14

They may become internalized within endothelial cells

This allows them to escape detection by the immune system.

Question 15

What effect do bacteria have on valve tissue during infective endocarditis?

Answer 15

They excrete enzymes that lead to destruction of valve tissue

This contributes to the proliferation of vegetative lesions.

Question 16

Explain the pathophysiological mechanism of infective endocarditis

Answer 16

1. injury to the endothelium –> exposes extracellular matrix proteins
2. coagulum of platelets, fibrinogen, fibronectin, and fibrin develops
3. fibronectin receptor on platelets and extracellular matrix proteins bind bacteria that contain microbial surface components recognizing adhesive matrix molecules (MSCRAMMs)
4. microorganism becomes embedded and incorporated into a vegetative lesion and multiplies –> severe MR + CHF

Question 17

What are the highest risk factors for thromboembolic disease in people with IE?

Answer 17

• mitral valve involvement
• large mobile vegetative lesions > 1-1.5 cm
• increasing lesion size during antimicrobial therapy

Question 18

What is the most common sequela of infective endocarditis (IE) in both dogs and cats?

Answer 18

Congestive heart failure (CHF)

CHF is the most common cause of death in cases of IE.

Question 19

What immune-mediated diseases are commonly seen in dogs with infective endocarditis? What is their prevalence?

Answer 19

Polyarthritis (75%) and glomerulonephritis (36%)

75% of dogs with IE show polyarthritis, and 36% show glomerulonephritis.

Question 20

Name the circulating immune complexes in IE

Answer 20

IgM, IgG, and C3 (complement)

This helps in diagnosing potential septic arthritis.

Question 21

What is the significance of the urine protein:creatinine ratio in dogs with proteinuria?

Answer 21

It supports the diagnosis of glomerulonephritis

This evaluation is crucial for confirming the condition.

Question 22

Name 2 types of thromboembolism as a sequel to infective endocarditis in dogs?

Answer 22

Septic and aseptic thromboembolism

Documented in 70% to 80% of dogs with IE.

Question 23

What are the most common sites of infarction in dogs suffering from thromboembolic disease?

Answer 23

Kidneys and spleen

Myocardium, brain, and limbs are also affected.

Question 24

What is the most common CNS thromboembolism location in people and dogs?

Answer 24

Middle cerebral artery

This can lead to brain ischemia and possibly ischemic necrosis.

Question 25

True or False: Vascular encephalopathy occurs in approximately one-third of people with infective endocarditis.

Answer 25

True ## Footnote It is uncommon in dogs.

Question 26

What is the incidence of thromboembolism in dogs with IE?

Answer 26

documented on pathology: 70% - 80% suspected clinically antemortem: 44%

Question 27

What breeds are overrepresented for IE?

Answer 27

Labrador Retriever, German Shepherd, Boxer, and Golden Retriever.

Question 28

List the most common presenting sings for IE

Answer 28

lameness! lethargy anorexia respiratory abnormalities weakness collapse Others (less common): Neurologic abnormalities (i.e., seizures, ataxia, deficits of conscious proprioception, obtundation, cranial nerve deficits, and vestibular signs), vomiting, and epistaxis are less common presenting complaints.

Question 29

Which structural heart disease significantly predisposes dogs to the development of infective endocarditis?

Answer 29

Subaortic stenosis ## Footnote It is the only cardiac disease statistically identified as a predisposing factor for IE.

Question 30

List 7 common sources of bacteremia in dogs.

Answer 30

* Diskospondylitis * Prostatitis * Pneumonia * Urinary tract infection * Pyoderma * Periodontal disease * Long-term indwelling central venous catheters ## Footnote These conditions can lead to the presence of bacteria in the bloodstream, increasing the risk for IE.

Question 31

What did a more recent investigation find regarding Enterococcus spp. and infective endocarditis?

Answer 31

Identical strains found in the mouth and IE lesions in 32 dogs ## Footnote This suggests a potential link between oral bacteria and the development of IE.

Question 32

When are prophylactic antimicrobials recommended for dogs?

Answer 32

dogs with subaortic or valvular aortic stenosis undergoing dental procedures/surgery ## Footnote This practice aims to prevent bacteremia during such high-risk procedures.

Question 33

What type of antimicrobials can be administered before and during a procedure?

Answer 33

Broad-spectrum antimicrobials (first-generation cephalosporins, ticarcillin) ## Footnote These should be given 1 hour prior to the procedure.

Question 34

List the modified DUKE's criteria for the diagnosis of IE

Answer 34

Major Criteria: 1. Positive echocardiogram Vegetative, oscillating lesion Erosive lesion Abscess 2. New valvular insufficiency 3. More than mild AI in absence of subaortic stenosis 4. Positive blood culture ≤ 2 positive blood cultures ≥ 3 with common skin contaminant Minor Criteria: 1. Fever 2. Medium to large dog (>15 kg) 3. Subaortic stenosis 4. Thromboembolic disease 5. Immune-mediated disease - Polyarthritis - Glomerulonephritis 6. Positive blood culture not meeting major criteria 7. Bartonella serology ≥ 1:1024 Diagnosis: Definite: Pathology of the valve, 2 major criteria OR 1 major and 2 minor criteria Possible: 1 major and 1 minor criteria OR 3 minor criteria Unlikely: Other diagnosis made, resolved in <4 days of treatment, no evidence at necropsy

Question 35

What are the 3 most common causes of infective endocarditis (IE) in dogs?

Answer 35

* Staphylococcus spp. (S. aureus and S. pseudintermedius, and coagulase negative Staphylococcus) * Streptococcus spp. (S. canis and S. bovis) * Escherichia coli ## Footnote Includes S. aureus, S. pseudintermedius, coagulase negative Staphylococcus, S. canis, and S. bovis.

Question 36

List less common bacterial isolates causing infective endocarditis in dogs.

Answer 36

* Enterococcus spp. * Pseudomonas spp. * Erysipelothrix rhusiopathiae * Enterobacter spp. * Pasteurella spp. * Corynebacterium spp. * Proteus spp. ## Footnote These bacteria are not typically the primary causes of IE.

Question 37

What percentage of dogs in Northern California with negative blood cultures had IE caused by Bartonella spp.?

Answer 37

45% (overall 28%) ## Footnote This highlights the importance of testing for bartonellosis in dogs with IE.

Question 38

Which species of Bartonella is the most important cause of IE in dogs?

Answer 38

Bartonella vinsonii spp. berkhoffii ## Footnote This species is specifically noted for its role in canine infective endocarditis.

Question 39

Which heart valve is primarily affected by Bartonella spp. in dogs?

Answer 39

Aortic valve ## Footnote The mitral valve is less commonly affected.

Question 40

What concurrent sero-reactivity is common in dogs with IE caused by Bartonella spp.?

Answer 40

Anaplasma phagocytophilum, Ehrlichia canis, Rickettsia rickettsii ## Footnote Testing for tick-borne diseases is recommended for seroreactive dogs.

Question 42

What percentage of dogs with infective endocarditis (IE) are reported to have a murmur?

Answer 42

89% to 96% ## Footnote This statistic reflects the high prevalence of murmurs in dogs diagnosed with IE.

Question 43

In a study, what percentage of dogs with IE had a new murmur?

Answer 43

41% ## Footnote This indicates that not all dogs with IE present with a new murmur.

Question 44

What clinical findings should trigger suspicion of aortic valve IE?

Answer 44

Diastolic murmur and bounding femoral pulses ## Footnote Diastolic murmurs are often low in intensity, making them hard to identify.

Question 45

What is the range of fever occurrence in dogs with IE?

Answer 45

50% to 74% Less likely in Bartonella spp. ## Footnote Fever may be masked by concurrent antimicrobial therapy in some cases.

Question 46

What percentage of dogs with IE experience arrhythmias?

Answer 46

40% to 70% ## Footnote Arrhythmias are a common complication in dogs diagnosed with IE.

Question 47

List the types of arrhythmias commonly seen in dogs with IE in order of frequency.

Answer 47

* Ventricular arrhythmias * Supraventricular tachycardia * Third-degree atrioventricular block * Atrial fibrillation ## Footnote These arrhythmias can arise due to various complications associated with IE.

Question 48

What percentage of dogs with aortic valve IE develop ventricular arrhythmias?

Answer 48

62% ## Footnote This statistic emphasizes the high risk of ventricular arrhythmias in these cases.

Question 49

What is the prevalence of CHF in dogs with IE?

Answer 49

Almost 50% ## Footnote CHF can occur due to the acute nature of the disease.

Question 50

What percentage of cases show CHF without left atrial dilation?

Answer 50

75% ## Footnote This statistic suggests that CHF can manifest acutely in IE cases.

Question 51

What are reported coagulation changes in dogs with IE?

Answer 51

* elevated D-dimer or FDPs (87%) *hyperfibrinogenemia (83%)

Question 52

What are reported renal complications in IE? What % of dogs with IE develop renal complications?

Answer 52

50% * prerenal or renal azotemia * glomerulonephritis * pyelonephritis *renal thrombosis

Question 53

How common in moderate to severe renal failure in dogs with IE?

Answer 53

33%

Question 54

What are the most common abnormalities on urinalysis in dogs with IE?

Answer 54

* cystitis (60%) * proteinuria (50% to 60%) * hematuria (18% to 62%)

Question 55

What % of dogs with IE had an increased UPC?

Answer 55

77% --> moderate or severely elevated in 58% of these dogs

Question 56

What is the cornerstone of diagnosing infective endocarditis (IE) in dogs?

Answer 56

Identification of a vegetative valvular lesion on echocardiography (ECHO) or at necropsy ## Footnote The pathognomonic echocardiographic lesion is a hyperechoic, oscillating, irregular-shaped mass.

Question 57

What does a pathognomonic IE lesion look like on echocardiography?

Answer 57

hyperechoic, oscillating, irregular-shaped (i.e., shaggy) mass adherent to, yet distinct from, the endothelial cardiac surface

Question 58

What is always present in the affected valve in cases of infective endocarditis?

Answer 58

Valvular insufficiency

Question 59

What percentage of cats had the aortic valve affected by infective endocarditis (Palerme et al JVC 2016)?

Answer 59

62%.

Question 60

What percentage of cases affected the mitral valve (Palerme et al JVC 2016)?

Answer 60

38%.

Question 61

What percentage of blood and urine cultures are frequently negative in dogs with infective endocarditis?

Answer 61

60% to 70% ## Footnote This is due to concurrent antimicrobial use in a majority of dogs.

Question 62

What is the recommended technique (sites, blood ml, time interval etc.) for blood cultures?

Answer 62

Three or four blood samples 5-10ml each at least 30min to 1hr apart from different venous sites if under Abs then collect at estimated trough of drug level ## Footnote Each sample should be 5 to 10 ml and collected aseptically from different venous sites.

Question 63

Why is it important to collect adequate volumes of blood for culture?

Answer 63

Because the concentration of bacteria in blood is very low (less than 5 to 10 bacteria/ml)

Question 64

What combination of tests identified bacteria in 61% of dogs with suspected infective endocarditis?

Answer 64

Blood culture and PCR of 16S rDNA

Question 65

What were the identification rates for bacteria using blood culture and PCR alone?

Answer 65

33% for blood culture and 39% for PCR alone

Question 66

Why is routine culture not recommended for Bartonella spp.?

Answer 66

They are fastidious organisms that rarely grow on culture medium

Question 67

What specific culture medium is recommended for Bartonella spp.?

Answer 67

Bartonella alpha proteobacteria growth medium (BAPGM)

Question 68

How long should Bartonella spp. be cultured on BAPGM before further processing?

Answer 68

≥ 1 week

Question 69

What follow-up process is recommended after culturing Bartonella spp. on BAPGM?

Answer 69

Plating on agar for up to 5 weeks

Question 70

What % of dogs with IE was positive on direct PCR on serum with bartonellosis? How did this change after prolonged incubation (for up to 1 month) in special enrichment media?

Answer 70

13% --> 66%

Question 71

What type of antimicrobials are typically used in human medicine for IE?

Answer 71

Aggressive broad-spectrum, bacteriocidal IV antimicrobials. ## Footnote Up to half of patients may require surgery for valve replacement.

Question 72

Why are antimicrobials often administered for a long period of time (up to a year)?

Answer 72

lack of vascularity within the vegetative lesion and the impaired host defense against bacteria tightly encased in a fibrin meshwork, free from phagocytes ## Footnote This is due to the lack of vascularity in vegetative lesions and impaired host defense.

Question 73

What combination of antimicrobials is recommended for patients without renal disease?

Answer 73

Ampicillin/sulbactam and amikacin. ## Footnote This is based on local data from UC Davis.

Question 74

What combination of antimicrobials is recommended for patients with renal disease?

Answer 74

Ampicillin/sulbactam and enrofloxacin or a third-generation cephalosporin. ## Footnote Options include ceftazidime or cefotaxime.

Question 75

How long is intravenous antimicrobial therapy typically required for acute aggressive treatment of IE?

Answer 75

1 to 2 weeks. ## Footnote Chronic hospitalization and expensive treatment may be needed.

Question 76

What is the duration for chronic long-term oral antimicrobials after initial intravenous therapy?

Answer 76

At least 6 to 8 weeks or longer. ## Footnote This is necessary after the initial 1 to 2 weeks of intravenous treatment.

Question 77

What may indicate the need to switch antimicrobials during therapy?

Answer 77

Lack of improvement in an oscillating vegetative lesion after the first week of therapy. ## Footnote This may suggest a more aggressive, resistant bacterium.

Question 78

What is often used for treatment of Bartonella spp. infections in dogs?

Answer 78

doxycycline, azithromycin, fluoroquinolones, amoxicillin/clavulanate, and aminoglycosides. Azithromycin has the least minimum bactericidal activity against Bartonella spp. ## Footnote At least 2 weeks of aminoglycosides improves survival in people.

Question 79

What has been observed regarding the use of aspirin in infective endocarditis treatment in people?

Answer 79

Increased bleeding episodes and no benefit in vegetation resolution or reduced embolic events ## Footnote This trend has been noted in humans with infective endocarditis.

Question 80

Fill in the blank: Anticoagulant therapy is not recommended for infective endocarditis due to increased _______.

Answer 80

bleeding episodes

Question 81

What type of lesions in infective endocarditis patients may necessitate surgical intervention?

Answer 81

Vegetative lesions larger than 10 mm ## Footnote These lesions pose a higher risk for thromboembolic complications.

Question 82

What is the median survival for dogs with aortic and mirtal IE according to Sykes et al JAVMA 2006?

Answer 82

aortic: 3 days mitral: 476 days ## Footnote This is significantly shorter compared to the median survival for dogs with mitral valve IE, which was 476 days.

Question 83

What is a common characteristic of dogs with Bartonella IE?

Answer 83

Short survival times due to aortic valve being affected almost exclusively ## Footnote This leads to grave prognoses similar to those seen in dogs with aortic IE.

Question 84

What was the reported mortality rate for dogs with aortic IE in the first week and 5 months (Sisson et al JAVMA 1984?

Answer 84

1st week: 33% 5 months: 92% ## Footnote This indicates a high risk of early death associated with aortic IE.

Question 85

List 5 risk factors for early cardiovascular death in dogs with IE.

Answer 85

* Glucocorticoid administration before treatment * Presence of thrombocytopenia * High serum creatinine concentration * Renal complications * Thromboembolic disease ## Footnote These factors can significantly worsen the prognosis.

Question 86

What are the most common causes of death soon after diagnosis of IE in dogs?

Answer 86

* CHF * Sudden cardiac death from a lethal arrhythmia Others: * Renal failure * Pulmonary hemorrhage * Severe neurologic disease ## Footnote These conditions are critical in the early mortality associated with IE.

Question 87

Berrezaie et al JSAP 2023: 1. most common organisms? 2. Most common valve affected? 3. STD + MST post discharge? 4. What was associated with poorer outcome?

Answer 87

1. Escherichia coli (26%), Pasteurella spp. (19%), Staphylococcus spp. (15%) and Corynebacterium spp. (15%). Bartonella spp. not detected. 2. Mitral valve - 62% 3. 69% - 425d (2-3650d) 4. CHF! --> cTnI, antithrombotics + development of thromboembolism or arrhythmias not significantly associated with outcome

Question 88

Reagan et al JVIM 2022: 1. STD? Median survival times? 2. Long-term survival? 3. Risk factors associated with mortality? 4. What was associated with surivival?

Answer 88

1. 70% - MST 72d 2. 45% 3. CHF (OR 12), thromboembolic events (OR 6), AKI (OR 6) 4. Administration of antithrombotic medications was associated with survival (OR 0.35). --> MST not treated with antithrombotics: 92 days --> MST treated with antithrombotics: still alive --> heart valves involved and etiologic agent did not correlate with outcome.