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Case of the week #13

MSSA Septic arthritis with large joint effusion and compressive lower extremity edema

In this patient with history of portal vein thrombosis on lovenox presenting with new unilateral lower extremity swelling, certainly DVT is on the differential. However with two negative lower extremity dopplers, other diagnoses must be considered. Fortunately with POCUS, the diagnosis was made in minutes. One of the benefits of POCUS is that when someone says "it hurts right here" or there is unexplained swelling, you can just place your probe on there and take a look. Often times you may be surprised by what you find.

The patient reported pain with minimal knee flexion. Close examination of his knee revealed some mild warmth to touch. These should point you in the direction of looking for an effusion. This case was confounded by the fact that he had pitting edema past his knee up to his mid thigh, not an expected finding in septic arthritis.

Suprapatellar effusion


Parasternal Long Axis View


A dilated right ventricle partially seen on​ the parasternal long view. Even in this limited RV slice, you can see that it is similar in size to the left ventricle. For a better appreciation of the RV size relative to the LV, the parasternal short and apical 4 chamber view are much more useful.

Right Ventricle

Left Ventricle

Parasternal Short Axis View


In short axis, comparing LV and RV is more straightforward. A normal​ right ventricle is more of a crescent moon shape while a normal left ventricle is circular. In this patient, the RV has expanded into an orange-slice shape, and flattened the septum, turning the left ventricle into a D-shape.

The 'D sign' or flattening of the interventricular septum is not sensitive for PE or other signs of right heart strain but is specific for causes of right heart strain. In this patient with no previous echo to compare, an acute PE must be ruled out with a CT chest angiography study.





Apical 4 chamber view

In the apical view, it is extremely important to orient yourself and your probe before interpreting the image. Normally the LV would be larger and you can identify it that way. In this patient, the RV is larger, so if your probe marker is accidentally on the wrong side, you may interpret this as a normal study. 

This RV is larger than the LV which would qualify as severe RV dilation. For more on how to properly acquire these images go here.

Assessing the right ventricle


Since it usually pumps against low pressures, the RV has a thin wall and is smaller than the left ventricle. If it is approaching the same size as the LV it already is moderately dilated, and severely dilated if larger than the LV. Another important aspect to look for is the dominant chamber at the apex. When the RV becomes the dominant ventricle represented at the apex, this is further evidence that RV dilation has occured.

RV Shape

As noted in the parasternal short axis view above, the RV is normally a small, crescent-moon shape while the LV is more circular. When there is RV dilation, the RV chamber switches to a more orange-slice shape and enlarges.

Normal Heart

Right heart strain

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Acute vs Chronic RV failure

As the condition becomes more chronic, the RV wall thickness will increase to deal with the chronically elevated pulmonary pressures. This can be a clue as to how acute or chronic the RV dilation is. Measured in subcostal 4 chamber view, a normal RV wall thickness should be less than 5mm. If it is greater than 1cm, it is likely a chronic process. Of course finding a thickened RV does not exclude a patient with a chronic RV dilation presenting with an acute PE.


RV systolic function

Like the left ventricle, an 'eyeball' approach or qualitative method is usually sufficient to be able to say it is normal or severely reduced.


For a more quantitative approach, the Tricuspid Annular Plane Systolic Excursion (TAPSE) is employed. This is done by obtaining the apical 4-chamber view and placing the M-mode cursor over the tricuspid annulus, then measuring the side of the peak of one of the m-mode tracings

  • Decreased is defined as less than 1.6cm

For a quick and excellent tutorial on TAPSE, go here.

If no pulmonary embolus?

If there is no sign of pulmonary embolus, then other causes of elevated pulmonary pressures must be considered. There are 5 classes of pulmonary hypertension as defined by the WHO:

  • Group 1: pulmonary arterial hypertension

  • Group 2: elevated right sided pressures related to left heart disease (congestive heart failure, valvular disease)

  • Group 3: Lung diseases such as COPD, interstitial lung disease, obstructive sleep apnea

  • Group 4: Chronic Thromboembolic Pulmonary Hypertension (CTEPH) due to chronic small clot formation

  • Group 5: Pulmonary hypertension causes by other conditions

Pulmonary Arterial Hypertension (PAH) & Sirius Satellite Radio

PAH is a difficult to treat disease characterized by increasing pulmonary vascular resistance that eventually leads to RV failure and premature death. Up until 1994 there were no good treatment options. In 1994, Flolan (continuous infusion of epoprostinol) was approved. It is a prostacyclin that requires continuous infusion due to its short half life of only 6 minutes. The half life was so short that interruptions in infusion were life threatening. It was also not stable at room temperature, required ice packs at all times to keep the molecule stable. To top it off, the pump was 3-5 pounds, overall making for a terrible patient experience.

At around this time a person by the name of Martine Rothblatt would start on a journey that would eventually help save millions of lives.

Martine (at the time was still Martin Rothblatt), initially interested in space and satellite technology, studied law and focused on telecommunications, eventually working as a lobbyist and then at a company that made a precursor to the modern GPS of today. She had a dream to broadcast music she loved to all corners of the globe, not just via AM and FM frequencies.

After jumping through many hoops, changing broadcasting laws, developing grass roots support of such technology, she eventually founded Sirius Satellite Radio in 1990, what we now know as SiriusXM radio. 


The 'Jenesis' of a drug

A few years later in 1994 her daughter Jenesis was diagnosed with pulmonary arterial hypertension (PAH) at the age of 10 years old. At the time, the prognosis was very poor with only a few years to live without treatment.

When at the hospital with her daughter, Martine would go to the library and scour the literature on pulmonary hypertension, learning everything she could about the disease, eventually becoming an expert in this condition. She realized there was a possibility that a chemical called treprostinil may have a chance of working to treat PAH. A pharmaceutical company at the time, GlaxoWelcome, had the patent on this chemical, but was not in development for any treatment with no hope that it would work. After getting multiple rejections to buy the patent, eventually Martine teamed up with a retired pharmacologist named James Crow and GlaxoWelcome agreed to sell the patent and a small amount of the treprostinil for $25,000 and 10% of any revenue they may make on it in the future.

Eventually this developed into the drug we know today as Remodulin. Compared to Flolan, it is stable at room temperature, has a better half life of 3-4 hours, but still requires a pump and continuous infusion. It was an incredible achievement for a satellite technology expert, and it helped his daughter stay alive. 

Martine formed United Therapeutics and entered the pharmaceutical business. Since then they developed an inhaled version of treprostinil called Tyvaso,  and oral version called Orenitram (Martine Ro spelled backwards), and Adcirca, a PDE-5 inhibitor. Thanks in large part to her newly developed drugs, Martine's daughter Jenesis is still alive today, as are thousands of others who suffer from pulmonary hypertension.

Due to the remarkable success of United Therapeutics and Remodulin, every year they pay over $100M a year to GlaxoWelcome for that initial license of their treprostinil patent, quite a return on investment.


Martine (center) with her daugher Jenesis (left) and her wife Bina. via

Treating PAH in 2020

While this story is absolutely miraculous, the efficacy of the drugs have been questioned. Orenitram improved 6-minute walk time by 23 minutes in one study, but failed in another two (here and here). Remodulin on the other hand has been shown to be safe and effective in improving 6 minute walk test, pulmonary pressures and more.

Martine and United Therapeutics are investing heavily in "3D-printed stem cell-grafted organs using fiber from genetically altered tobacco plants, while simultaneously restoring previously unusable human lungs to functioning status through an ex-vivo lung perfusion technology that allows the lungs to be flushed and ventilated in isolation, and later re-evaluated for health and suitability for transplant. Also, in what may seem like the stuff of science fiction, at Revivicor, a subsidiary company in Blacksburg, Virginia, staff are producing genetically engineered pigs with organs that are directly transplantable into humans."

For more on Martine, we strongly recommend this TED talk from 2015.

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