Thread by @tony_breu

1/
Why is tricuspid valve (TV) endocarditis more common in those who use intravenous drugs?

The portal of entry for most bacteria is the venous system. If quick access to the right-heart were enough, TV endocarditis would be more common in everyone.

There must be more to it...

2/
In order to understand why the tricuspid valve is more commonly affected in those with IVDU, it is essential to first understand the pathogenesis of infective endocarditis.

So, a question: which of the following confers the greatest risk of infective endocarditis?

3/
Next, let's confirm that, in all comers, tricuspid valve involvement is relatively infrequent in infective endocarditis. One study reported the following rates:

35% aortic
29% mitral
14% aortic & mitral
9% tricuspid
1% pulmonic
2% left & right

ncbi.nlm.nih.gov/pubmed/12090865

4/
At least three steps are required for infective endocarditis (IE) to occur.

1. Endothelial injury
2. Activation of hemostasis with thrombus formation (i.e., nonbacterial thrombotic endocarditis, NBTE)
3. Secondary bacterial infection (i.e., IE)

ncbi.nlm.nih.gov/pubmed/4014276

5/
Regarding 1, vegetations rarely form on intact endothelium.

In the 1970s, Durack injected bacteria into rabbits. Some had catheter trauma (disrupting the endothelium); others did not. Results:

*no endothelial injury = no IE
*endothelial injury = IE

ncbi.nlm.nih.gov/pubmed/4700697

6/
Endothelial injury is more likely in areas of high pressure as this creates shear stress and disruption of the endothelium.

In 1952, Lepeschkin correlated the pressure resting on a closed valve with rates of IE.

higher pressure = higher rate of IE

ncbi.nlm.nih.gov/pubmed/14952510

7/
The result of endothelial injury is activation of the clotting cascade and creation of thrombus. Other factors fuel thrombus formation:

*high shear stress ➡️ platelet activation
*S aureus production of coagulase which converts fibrinogen to fibrin

ncbi.nlm.nih.gov/pubmed/21932963

8/
Given the above, which of the following might be used to prevent infective endocarditis?

9/
Both antiplatelets and anticoagulants have been suggested to prevent and/or treat IE.

The hypothesis: if we can reduce thrombus formation, maybe we can reduce infected vegetation formation and/or hasten resolution.

10/
As far back as the 1930s, heparin was tried as treatment for IE. Recall that this predates penicillins. The linked case report by Friedman is an example of what was used to treat IE:

Sulfanilamide
Quinine
Antistrep serum

Adding heparin didn't work.

jamanetwork.com/journals/jama/…

11/
There is some evidence suggesting that antiplatelets might reduce the risk of IE (PMID 17407036; Pic).

That said, the data is not conclusive and the use of antiplatelets and/or anticoagulants for the prevention or treatment is not recommended.

ncbi.nlm.nih.gov/pubmed/21932963

12/
With the pathogenesis of IE covered, we can now address the original question. Let's confirm that the tricuspid valve is more commonly involved in those with IVDU. One study found:

68% tricuspid
7% aortic
6% mitral
1% pulmonic

ncbi.nlm.nih.gov/pubmed/12866981

13/
Why this difference? The tricuspid valve (TV) has lower shear stress. And, again, bacteria enter the venous system in most situations (i.e., they "see the TV first").

What makes the TV more vulnerable in those with IV drug use?

14/
There are surely multiple factors, but endothelial injury to the tricuspid valve is likely a key event. And what causes this injury?

Particulate matter that comes with the injected material.

ncbi.nlm.nih.gov/pubmed/116317

15/
Interestingly, particulate matter >8-10 μm may not be able to pass through pulmonary capillaries, potentially "protecting" the aortic and pulmonic valves from this form of endothelial injury.

ncbi.nlm.nih.gov/pubmed/2197312

16/
There are many other factors that play a role in TV endocarditis, including:

*physiologic effects of injected substances (particularly cocaine)
*organism-specific factors (particularly S aureus)
*immune status
*bacterial load

ncbi.nlm.nih.gov/pubmed/10671344

17/
Before summing up, let's re-ask the original question.

Which of the following confers the greatest risk of infective endocarditis?

18/
Summary:
⭐️IE occurs after endothelial injury, thrombus formation, and bacterial infection of thrombus
⭐️In non-IVDU, the hemodynamics of the left heart predispose to IE
⭐️In IVDU, particulate matter leads to TV endothelial injury and IE (among other factors!)