Cardiovascular manifestations of mast cell disease (Part 2 of 5)

Abnormalities of heart rate and rhythm can occur due to action of several mast cell mediators. Histamine binds at histamine receptors numbered in the order of identification: H1, H2, H3 and H4. Histamine binding at H1 receptors on cardiomyocytes (heart muscle cells) slows the heart rate, while histamine binding at H2 receptors increasing heart rate and the force of heart contraction.

As I mentioned in the previous post, histamine binding at the H3 receptor decreases the release of norepinephrine. Another mast cell product, renin, modulates angiotensin II, which can increase norepinephrine release.  Increased levels of norepinephrine triggers increases in heart rate and force of contraction.  This means that whether or not mast cell activation causes tachycardia depends largely on how much renin and histamine are released. Much less histamine is necessary to trigger the H3 inhibition of norepinephrine release relative to the amount needed to affect heart rate through H1 and H2 receptors.

Prostaglandin D2, a mast cell mediator, can also cause tachycardia.  Of note, prostaglandin D2 is not stored in mast cell granules.  It is made following mast cell activation and is considered part of the “late phase allergy response”, which can occur several hours after exposure to a trigger.

Tachycardia is a common symptom for mast cell patients.  The recommendation in a recent review article is to treat when the heart rate is perpetually over 100-120 bpm, or when it is extremely distressing to the patient. There are a number of options for treatment. As it can be caused directly by mast cell behavior, mast cell medications such as antihistamines (H1 and H2) should be adjusted for maximum effect. Renin inhibitors, such as aliskiren (Tekturna in the US), can be used to treat supraventricular tachycardia (SVT) in mast cell patients, as can angiotensin receptor blockers like losartan, valsartan and others. Patients on renin inhibitors or angiotensin receptor blockers can also decrease blood pressure.

Calcium channel blockers, like verapamil, are also an option.  The medication ivabradine treats tachycardia in patients who have a regular heart rhythm and does not affect blood pressure.  Ivabradine is not used to treat atrial fibrillation. β-blockers are contraindicated in mast cell patients because it interferes with the action of epinephrine, making patients more likely to have reactions and epinephrine less likely to treat effectively.


Kolck UW, et al. Cardiovascular symptoms in patients with systemic mast cell activation disease. Translation Research 2016; x:1-10.

Gonzalez-de-Olano D, et al. Mast cell-related disorders presenting with Kounis Syndrome. International Journal of Cardiology 2012: 161(1): 56-58.

Kennedy S, et al. Mast cells and vascular diseases. Pharmacology & Therapeutics 2013; 138: 53-65.

10 Responses

  1. Sue Hargrave April 22, 2016 / 10:49 pm

    Thank you, Lisa! I just recently had a heart issue, and I would never have linked it to Chronic Urticaria. It still may not be connected, but I’m going to be having quite a conversation with my Cardiologist about the bundle blockage and it’s impact on me, as I was taken away in an ambulance, and then had all kinds of testing, which is how I found out about the bundle blockage. Very interesting. As always, thank you!

  2. irish willow April 23, 2016 / 3:48 am

    I once was taken into er and the Dr. said I had no mechanical blockage, but I did show heart block. could this have been from mastocytosis
    ps you doing okay.

    • Lisa Klimas April 23, 2016 / 10:02 pm

      It could have been, yes. I’m extending the series to four posts so I can cover this, it’s a good topic that I forgot about in the first three posts.

      I am doing okay. Thanks for asking. 🙂 I have been really stressed recently, nothing in particular, I just have a lot of responsibilities and everything kind of converged. But it has been warm out this week and I’ve had a relaxing weekend and that always helps. Hope things are well with you.

  3. Donna Bianco Costarella April 23, 2016 / 5:37 am

    I think this is happening to me how can I be tested? Can it come and go? Thank You

    • Lisa Klimas April 23, 2016 / 10:00 pm

      Can mast cell disease come and go or can the cardiovascular symptoms come and go?

  4. Donna Bianco Costarella April 23, 2016 / 5:38 am

    to me how can I be tested? Can it come and go? Thank You

  5. Michelle Dellene April 23, 2016 / 1:45 pm

    I’m really enjoying all your posts, Lisa. I wonder if you have or could address traveling with masto/mcas? I sort of winged a post about it at my own blog, but I have a feeling you would do a much better job with the topic. 🙂

  6. becca April 26, 2016 / 3:13 pm

    In part one of this remarkably useful series, which my somewhat famous cardiologist has been humble enough to appreciate and learn from, you note that m.c. disorders are tied to aneurysms.

    1. m.c.disorders are linked to Ehlers-danlos, which means weakened blood vessels and, probably, higher stroke risk: but are there stats on the cross-over between EDS and m.c. disorders? You can have EDS w/o M.C. But how many have M.C. w/o EDS?
    2. are there stats on strokes in the M.C disorder population compared to the general population?

    Thank you for the research, and for writing with such honesty, clarity and poetic analogies.

  7. Isabella Quigley Moriarty April 28, 2016 / 3:21 am

    Thank you for your work and helpful information, Lisa. My sister died of a aortic aneuryism after three trips over the previous months to the emergency room — she was told she had allergies and was given meds to ‘calm’ her — this was almost twenty years ago but I noticed then the links between the ‘allergies’ and what we realised later were mini strokes. It was thought after she died that she could have had Marfans Syndrome. I appreciate your persistence in getting this materials together and out — thank you again. I find it healing as I feel confirmed in my own ‘knowing’ of what was happening then and also now feel empowered in sharing your site and information. Dr Sarah Myhill in the UK as done a lot of research on CFS/ME as being Low Output Heart Failure due to Mitochondrial Dysfunction. What I read here complements her research.

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