Cardiovascular manifestations of mast cell disease (Part 1 of 5)

Mast cells are present in the cardiovascular system under normal conditions both in the heart and near vasculature, often in spaces close to nerve endings.  They perform a variety of necessary functions including participating in the pathway to generate the hormone angiotensin II, which encourages an increase in blood pressure.  Mast cells in the heart and vasculature are usually positive for both chymase and tryptase in granules. Mast cells in the cardiovascular system have also been tied to a number of conditions, including atherosclerosis, arrhythmias and aneurysm.

Mast cell patients may experience a number of cardiovascular symptoms or events. 29% of SM patients and at least 20% of MCAS patients report palpitations and supraventricular tachycardia.  31% of patients with mast cell activation disease (MCAS, MMAS, SM) experience episodic or chronic elevation in arterial blood pressure due to mast cell activation. Ventricular fibrillation, cardiac arrest and Kounis Syndrome can occur in mast cell patients due to mast cell activation.  Few cases of heart failure in SM patients have been reported.

Kounis Syndrome is an acute coronary syndrome provoked by mast cell mediator release. In one series, ten mast cell patients (5 MCAS, 3 MMAS, 2 ISM) suffered acute coronary syndromes.  These patients reported “oppressive” chest pain of the type commonly seen in ischemic cardiac events.  The triggers for these events were diverse: venom immunotherapy, mepivacaine, exercise, penicillin, general anesthesia, wasp sting, metamizole and moxifloxacin.  In seven patients, the echocardiogram was normal.  In the remaining, left ventricular hypertrophy, anteroseptal hypokinesia, medioapical hypokinesia, inferoseptal akinesis, lateral apical akinesia and left ventricular ejection fraction of 40% were found on echo. Only six patients had elevation of troponin, a test commonly used to diagnose heart attack and acute coronary syndromes.

Mast cell mediators exhibit a wide range of effects on the cardiovascular and nervous systems. Mast cell mediators can affect release of norepinephrine by sympathetic nervous system, contributing to arrhythmias.  In some instances, release of norepinephrine has been linked to sudden cardiac death, although not linked specifically to mast cell patients. Histamine actually decreases norepinephrine release by binding to H3 receptors on nerve endings.

As mentioned above, mast cells participate in modulating the level of angiotensin II. Mast cells release renin, which leads to the formation of angiotensin II. Angiotensin II then binds to AT1 receptors on sympathetic nerve endings, raising blood pressure. Angiotensin II can also cause arrhythmias without involving the nervous system.

References:

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 & Therapeurics 2013; 138: 53-65.

7 Responses

  1. Colleen Pisaneschi April 18, 2016 / 8:24 pm

    Thank you thank you thank you, finally an explanation of what happened to me last year – you are the MASTer !!! Yet another wonderful post!

  2. Mark April 18, 2016 / 8:31 pm

    Perhaps this comment is premature not knowing what will appear in Parts 2 and 3 — ioncluding references to publications from Prof Kounis with and without Spain’s REMA, the US’s Dr. Theoharides, and fro Prof Molderings focused less on acute syndrones.

    I’m also puzzled why the REPORTED incidence of KOUNIS incidence of Kounis Syndome would be relatively less with SM. Perhaps because MCAS/D typically gets diagnosed — Is the incidence ofanaphylaxis in contrast to SM w/ UP especially — only in people who manifestly suffer severe attacks. Is the incidence of anaphylaxis respectively higher with MCAS/D too?

    https://mastopedia.wordpress.com/2016/04/10/cardiovascular-symptoms-in-patients-with-systemic-mast-cell-activation-disease/
    http://www.translationalres.com/article/S1931-5244%2815%2900454-5/abstract
    http://www.mastattack.org/2014/10/cardiovascular-symptoms-of-mcas/
    http://www.internationaljournalofcardiology.com/article/S0167-5273(11)00420-7/abstract
    http://www.internationaljournalofcardiology.com/article/S0167-5273(12)00816-9/abstract
    http://link.springer.com/article/10.1007%2Fs11739-013-1035-6
    https://mastopedia.wordpress.com/?s=kounis
    http://www.mastopedia.com/tiki-index.php?page=%22Mast+cell+activation+disorders+presenting+with+cerebral+vasospasm-related+symptoms%3A+A+%22Kounis-like%22+syndrome%3F%22

    • Lisa Klimas April 18, 2016 / 10:56 pm

      This is a good point about the SM vs MCAS. I think that is largely a function of sampling error. This patient series was very small. It is also not uncommon for both MCAS and SM to go undiagnosed for many years so I think in an emergency setting, the concept of allergic coronary artery syndromes are pretty far in the background. It is an artifact of the specialist nature of western medical systems, in my opinion.

      The brief answer to your question regarding anaphylaxis is that yes, both SM and MCAS exhibit much higher frequencies of anaphylaxis. For SM, I believe 51% have at least one anaphylactic episode requiring anaphylaxis in their lifetime. I wrote some posts about this, if you google “Mastattack anaphylaxis systemic mastocytosis” or search on the blog, it should come up. I think I wrote them in November 2014. The last paper I read that mentioned incidence of anaphylaxis in MCAS had some surprisingly low number like 20%. It is my personal feeling that this is also a sampling issue due to the difficulties in diagnosing MCAS. I personally think that MCAS patients experience more episodes of anaphylaxis than SM patients. I don’t have data to back this up, but I talk to a lot of people and I think that in this specific way, MCAS is actually more severe than SM.

      Kounis Syndrome is getting a very detailed series of its own. It reviews the literature from the last three years written by Kounis and others. I’m about halfway done with it, so should be done by the end of the month. Thanks for your thoughtful questions.

      • Mark April 19, 2016 / 6:51 pm

        Sorry my message appears so garbled. Not so bad on my computer screen but why the resulting , annoying discrepancy I have no idea, except I expect it’s on my end, or how mine fails to properly interact there. Unless something got mistakenly submitted from me as I typed, before I intended, before I got to review and edit and submitted as I intended, w/ at least diminished garbling.

        I realize the incidence of anaphylaxis is higher for both SM and those of us “clinically indistinguishable” in the words of the Vanderbilt SMCAD pioneers, and I believe at least some others in their wake. My impression was in line with years — that incidence of anaphylaxis is respectively HIGHER w/ MCAS. I suspect this is so, as I tried to articulate, because MCAS doesn’t get diagnosed unless patients suffer severe, episodic mediator symptoms. SM without UP is also less apt to be diagnosed absent severe episodic symptoms.

        A huge wrench is Dr. Akin’s dictate instructing doctors on http://www.UpToDate.com (I believe widely used, influential) Not to diagnose MCAD/S in patients suffering recurring Anaphylaxis. Ludicrous, cruel. As it is, I cannot qualify for what he proposed first w/ Dr. Metcalfe, Prof. Valent — then w/ others as their so-called “MCAS” “Consensus” Proposal — because they require testing unavailable to me, as at the ER of Dr. Akin’s hospital, and because they require a “symptom-free” period to get a “baseline” result on the same test(s). They pretend people like me don’t exist in Masto-world: people who essentially never suffer less than than severely from their mediator afflictions. Consequently, while I left my last visit to Dr. Akin’s institution with maximum Epipen prescription/refills, my latest medical record there reiterates my MCAS diagnosis from 4 different doctors yet incorrectly asserts I reported no anaphylaxis on my last visit. This despite reporting increased incidence/severity in the wake of very bad reactions to Xolair “off-label” followed by a bout of presumptive SARS/pneumonia leading to instructions that I quarantine myself as much as possible as my fever peaked at 106 F. My NYU MCAS expert here sidesteps Dr. Akin’s bizarre dictate by surmising — probably correctly — that my severe hypersensitivity reactions are at least largely Anaphylactoid, rather than clinically identical “Anaphylaxis” strictly speaking from IgE-mediated true allergies.

        I’m curious if you recall offhand the source of your figures on the reported incidence of Anaphylaxis w/ SM v. “MCAS.” The Dr. Castells/REMA article on “allergy” in some 210 Spanish mastocytosis patients reported Anaphylaxis history under/near 25%, I believe — embracing the Consensus clinical criteria for Anaphylaxis.

        The cruel “consensus” MCAS proposal from Drs. Akin, Metcalfe, Valent, followed by Dr. Akin’s incongruous Anaphylaxis exclusion, has almost certainly led doctors to employ different strategies in trying still to do right by us. Resulting in records documenting some lingo other than MCAS.

        REMA, for example, diagnoses “MCAD”, not “MCAS”, in Spanish patients with negative BMBs/aspirate analyses. Freon my perspective, the NYU specialist who first diagnosed, long treated, my “Systemic Mast Cell Disease” did not dichotomize people with the clinical presentation of (I)SM. Harvard’s Dr. Horan clinical assessment seemed substantively the same — telling me before any further test results that treatment recommendations for me were already at/near optimal given options available in 2003 US; and would be the same regardless what any marrow analysis would show with me: that my clinical presentation, med history clearly manifested MCAD if not SM.

        Indeed, my participation later in 2003 in this study resulted in recommendations to continue my heavy regimen of anti-mediator, stabilizing agents, epinephrine as necessary, without saying what the NIH recommended these for. Dr. Akin did not send me his evaluation letter as promised, but another participant had cannily advised me to also request all my records from NIH archives, and ultimately, my referring NYU dr. Dr. Akin seemed very unhappy his efforts to conceal this from me failed. He finally admitted he opposed diagnosing MCAD period — nothing particular to my case/evaluations as he had long insinuated with me and others. He incongruously referred to what some other specialist might ultimately find, while suggesting no potentially productive evaluations doctors had not already conducted with me. No alternative possible diagnosis consistent w/ my clinical presentation, responses to meds, triggers.

        https://clinicaltrials.gov/show/NCT00047918

        /Users/mark/Downloads/03-I-0010.1.AFlushi.030226-3-13.pdf

        • Lisa Klimas April 19, 2016 / 7:31 pm

          Hi, Mark,

          I will give a more detailed reply tomorrow but wanted to mention that I have never had the experience of refusing to draw serum tryptase at the BWH ER. I used to be in that ER pretty regularly for anaphylaxis and they never gave me a hard time. It is very possible that this depends on how the chart is noted.

          The paper wasn’t comparing SM and MCAS anaphylaxis rates, they were described in two different papers. I did a series on disease progression and prognosis and I think it is referenced there, but will check.

  3. Michelle Dellene April 22, 2016 / 11:17 am

    I have a lot of cardiovascular symptoms so this really helps me to understand the mechanics of what’s happening to me. Something I get that really baffled my doctors was skipping heartbeats whenever they gave me a prescription med that I reacted to. I don’t get it otherwise but I do get terrible tachycardia and chest pains. I have thought many times I was having a heart attack but like every else it goes away when the flare is over. Years ago I even had a 24hr monitor put on me but of course it didn’t show anything and I’m sure the doctors thought I was neurotic. Figures. :/

  4. Sarah April 30, 2016 / 3:02 pm

    Do you know how they diagnosed the acute coronary syndromes if they had normal echos and normal troponin levels?

Comments are closed.