The commonest symptom that brings a HCM patient to a physician is exertional dyspnea, followed by syncope and, of course, the unpredictable fatality.
Video courtesy Minneapolis Heart Institute Foundation
What is the mechanism of exertional dyspnea in HOCM?
Is it the obstruction or the restrictive diastolic function? It is easier to say both are equally responsible. Of course, that could be the correct answer, but a true academician need to go further. Among the two ,which is the dominant mechanism ?
As we are wondering what exactly causes dyspnea in HOCM … If we think for a minute, a simple fact seems to clarify everything. Try answering this question. Is dyspnea more common in obstructive HCM or non-obstructive HCM? The answer is not an unequivocal yes .There is definitely no linear correlation between dyspnea and degree of obstruction. This clearly tells us obstruction is not the primary culprit. We got the answer already. (Ref 3)
Other mechanisms: Dyspnea due to reduced forward output is rarely an issue. Associated MR can be a significant factor as MR – v wave pulses can directly trigger the pulmonary venous receptors. High intraventricular pressure stretching the LV mechanoceptors is also a reason. (Its more important in syncope though) In elderly, associated ischemia and CAD can contribute to dyspnea.
Clinical implication of this question
HOCM is a mystery genetic disease, with total myocardial disarray. Still, patients are blessed with hyper-contractile ventricles. No one understands how this is possible. What we need to do is pacify these aggressive contractions. That’s why beta blockers and calcium blockers have been used for decades. Now Mavacamten is introduced to correct the basic defect.
Mavacamten is a new class of drug that targets and corrects the underlying molecular defects of HCM .It is a Selective cardiac myosin inhibition , Reduces active myosin heads by reducing the number of myosin heads that can enter the active, force-generating state. Mavacamten stabilizes myosin in an inactive, energy-sparing conformation known as the “super-relaxed state.” This results in decreases contractility . Relieves LVOT obstruction and indirectley improves diastolic fucntion. lower filling pressures.
Is Mavamten really worthy ? What is the indication ?
Basically, it is a negative inotropic agent. Mind you, beta blockers are a great class of Nobel Prize-winning wonder drugs for this purpose. Calcium blockers too play an important role. But,we are living in a new age, a new era. We have to move on in life, hence we are forced to switch to different agents whether we like it or not, whether it works or not.
What does the evidence say?
Mavacamten is proven to be useful in HOCM in the VALOR-HCM trial published in JACC 2022. Though the MAVERICK trial showed some promise in non-obstructive HCM, the recent 2025 [ODYSSEY-HCM trial](DOI: 10.1056/NEJMoa2505927) did not provide any positive benefits.
Final message
Every patient of HOCM turns out to be clinically, and hemodynamically a full-blown HFpEF and even technically an RCM-plus. In this context, drug research must be directed at more positive lusiotropic agents (Than negative Inotropics) and anti-fibrotic drugs.
Coming to the title question, if I can manipulate the cardiology linguistics , it can be concluded like this. In HCM/HOCM, the primary symptom is diastolic dyspnea due to restriction and the systolic dyspnea due LVOT obstruction contributes a lesser degree. ( Then why all this Septal reduction stuff ? Please don’t ask this question)
Reference
The dyspnea paradox : HCM might be more symptomatic than HOCM , especially in the early stages
3.M Lowe, J Jackson, Y Zhong, M Contente, L Le Brocq, S Barlow, T Krause, Clinical characteristics and burden of non-obstructive hypertrophic cardiomyopathy: a real-world survey in Italy and Spain, European Heart Journal, Volume 45, Issue Supplement_1, October 2024, ehae666.2021, https://doi.org/10.1093/eurheartj/ehae666.2021
Next question: Is Incidence of syncope linearly related to the severity of LVOT obstruction?
Let us take more time to find the correct answer.
Dr.S.Venkatesan MD 