Limits to submaximal and maximal exercise in patients with hypertrophic cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HCM) often have reduced exercise capacity, and it is unclear whether cardiovascular regulation during exercise is intact in these patients. We aimed to determine the relationship between cardiac output (Q̇) and oxygen uptake (V̇o), and stroke volume (SV) reserve in HCM compared with healthy participants and participants with left ventricular hypertrophy (LVH) but not HCM. Sixteen patients with HCM (48 ± 7 yr, 44% female), 16 participants with LVH (49 ± 5 yr, 44% female), and 61 healthy controls (CON: 52 ± 5 yr, 52% female) completed submaximal steady-state treadmill exercise followed by a maximal exercise test. V̇o, Q̇, SV, and arteriovenous oxygen difference were measured during rest and exercise, and Q̇/V̇o slopes were constructed, The Q̇/V̇o slope was blunted in HCM compared with CON and LVH [HCM 4.9 ± 0.7 vs. CON 5.5 ± 1.0 ( = 0.027) vs. LVH 6.0 ± 1.0 AU ( = 0.002)] and participants with HCM had a lower SV reserve (HCM 53 ± 33%, controls 83 ± 33%, LVH 82 ± 22%; HCM vs. controls = 0.002; HCM vs. LVH = 0.015). Despite a blunted Q̇/V̇o slope, 75% of patients with HCM achieved ≥80% predicted V̇o by augmenting a-vo difference at maximal exercise (16.0 ± 0.8 mL/100 mL vs. 13.8 ± 2.7 mL/100 mL, = 0.021). Patients with HCM do not appropriately match Q̇ to metabolic demand, primarily due to inadequate stroke volume augmentation. Despite this central limitation, many patients achieve normal exercise capacities by significantly increasing peripheral oxygen extraction. Through state-of-the-art hemodynamic and oxygen uptake methodologies, this study found the cardiac output response to increasing metabolic demand is blunted among patients with hypertrophic cardiomyopathy (HCM), primarily due to a reduced stroke volume reserve. Many patients with HCM augment their peripheral oxygen extraction during maximal exercise to achieve normal exercise capacity and overcome ineffective matching of cardiac output. Peripheral adaptations that compensate for cardiac limitations may contribute to the heterogeneity of functional limitations observed within this patient population.