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On Apr 30, 2015, at 3:02 PM, "Dima Turpin" <dturpin11@gmail.com> wrote:
Hello colleagues,
I am taking care of a new patient who has homozygous familial hyperlipidemia confirmed by genetic testing in the past at the National Institute of Health ( NIH) in Maryland where she used to see a lipidologist for yearly evaluations. The family has tried to follow up with him but have not had any success due to busy lines or no reponse. They were told the funding for that program is no longer there.
She is a lovely 10 year old whose parents had very high cholesterol in the 400s for dad and 300s for mom prior to their treatment. This prompted her PCP to check Her Cholesterol which was very high: total 779 mg/dl, LDL 770. She is now taking atorvastatin 20 mg daily and zetia 10 mg dail. Her most recent LDL was 318 mg/dl. She has xanthomas on her left elbow and arcus bilaterally in her corneae. Her cardiac exam reveals an ejection systolic murmur in the aortic region which radiates to the neck. She has normal blood pressures and a normal BMI. ECG is normal. Echocardiogram reveals thickening in the aortic root region with some resultant flow acceleration across the supravalvar region of 2.4 m/s. There is no significant pressure gradient peak gradient 23 mmHg. Her mitral valve annulus also appears thickened and possibly calcified to some degree, there is mild mitral regurgitation. She has normal biventricular size and systolic function.
I added Cholestyramine to her regimen 4 grams daily.
The aortic root has an appearance of atheroma build-up. I ordered cardiac CT angiography to evalaute her aorta and coronaries. Her CIMT at the INH was normal in 2013. Stress test was normal.
Does anyone have experience as to imaging in these patients? I think that's not the correct wording to use, because this disease is like 1:1,000,000, what I meant is I am trying to get imput to optimally manage her. I am considering a heart catheterization although this is not our area of expertise in the pediatric world if she needs coronary intervention.
Would anyone consider this patient for LDL apheresis?
Your input is greatly appreciated.
Dima Turpin, MD, FAAP
Johns Hopkins All Childrens Heart Institute
Saint Petersburg, Florida
On Apr 30, 2015, at 3:55 PM, Gidding, Samuel <Samuel.Gidding@nemours.org> wrote:
Needs apheresis. We have an MRI imaging protocol. May be a candidate for a drug trial. What is the genotype?
Sam Gidding
Thank you Lisa and Sam so much for the responses. This is greatly helpful. And yes ok to post on PedAL.
Sam, I do not have results of the genetic testing we are trying to get a hold of the INH where parents said it was done
Thank you again so much. I will look up centers to see where we can send her for apheresis.
From
Dima Turpin
Agree with apheresis if you can find a center. We’ve used a double lumen Vortex 11.5 Fr. port for access in our patients, youngest was 6 years but Lisa has been successful in achieving apheresis with even younger children. The International Society for Apheresis might be a good place to start when looking for an aphaeresis center, it’s currently chaired by Patrick Moriarty who has a lot of experience with apheresis in adults. I am working on using alirocumab PCSK9 agent for 1 or our patients, compassionate use, - will see how things go. I haven’t used the other novel agents but those would be alternatives if you aren’t near an aphaeresis center.
If I’m understanding this correctly your patient is on atorva 20, you have lots of room to go up, relatively rapidly, to atorva 80 or rosuvastatin 40. You could move up that dose while you’re working out these bigger interventions.
For coronary imaging, we’ve used CT angiography. Key is to drop the heart rate down substantially with a beta blocker so you can get the best quality images. For cath, we’ve used joint pedi and adult teams, with the procedure being done in an adult lab if we expect to intervene and in a pedi if we don’t. Important to have some type of a stress test first so that you can sort out what to do with intermediate lesions.
Best, Sarah de Ferranti
LDL apheresis, if available,would be a gold standard in this case.
A certain number of pediatric clinical trials in HoFH are ongoing or in preparation. One is in the recruitment phase with a PCSK9-inhibitor, a treatment which may be quite effective if she is not a null-allele HoFH;
Other possibilities include Lomitapide, PPAR delta agonists, ANGPTL3-inhibitors and eventually, HDL-peptide mimetics, among others. The pediatric population is discussed for all of them.
A pediatric trial with rosuvastatin is also ongoing in HoFH aged <18y.
Best,
Daniel Gaudet