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Approximately 10% of sudden cardiac deaths among patients under 35 years of age is owing to hypertrophic cardiomyopathy (HCM)-related cardiac arrest (CA). CA is often associated with pre-arrest or peri-arrest hypotension and is treated by a set of interventions, including the administration of epinephrine. It is debated whether epinephrine increases or decreases survival to discharge following CA. HCM is associated with septal hypertrophy with a dynamic left ventricular outflow tract obstruction and impaired peripheral vasoconstriction in response to α1-adrenergic stimulation, both of which could cause epinephrine to have a different effect than in the general population. This systematic review of the literature aimed to investigate if patients with HCM in CA have a detrimental hemodynamic response to epinephrine. A literature search was performed in October 2016 using Medline (OVID), Embase (Elsevier), and Cochrane Library (Wiley). The initial search generated 2429 articles, of which 22 articles were found to meet inclusion criteria: four physiology studies, 13 case reports of hypotensive HCM patients, and five case reports of HCM patients in CA. The reviewed studies demonstrate that epinephrine effect varies in patients with HCM: in some cases, the expected hypertensive effect was obtained, but in others, a paradoxical hypotensive effect, or no effect, was observed. The probable mechanism of this effect is an increased left ventricular outflow tract obstruction. Other drugs were considered in several of these cases. In summary, the retrieved studies jointly suggest that patients with HCM may respond differently to epinephrine than patients without HCM. The suitability of epinephrine in HCM-associated CA is questionable.