Exercise unmasks impaired vascular and cardiac hemodynamic in patients with hypertrophic cardiomyopathy

Abstract Background/Introduction Exertional dyspnea is a common finding in patients with Hypertrophic Cardiomyopathy (HCM), yet little data is available regarding the hemodynamic disturbances that lead to symptom development in this population. Purpose To investigate the mechanisms involved in the functional limitation of patients with HCM. Methods We prospectively studied 20 symptomatic patients with confirmed diagnosis of HCM. Assessment included NT-pro BNP levels, echocardiogram, and invasive characterization, where subjects also underwent invasive cardiopulmonary exercise testing. Results Median patient age was 57 (48–66) years old and 15 (75%) were male. Basal NT-pro BNP was elevated (748 pg/mL [406–1082]) and 8 (40%) subjects had NYHA functional Class III despite optimal medical treatment. Sarcomeric abnormal mutations were identified in 12 subjects (60%), most frequently in MYBPC3. Ultrasound imaging showed marked left ventricle (LV) hypertrophy (LV Mass Index 140 g/m2 [109–161]), with signs of LV outflow obstruction in 13 (65%) subjects. All patients displayed preserved ejection fraction (68% [61–73]). Significant mitral regurgitation was present in 5 subjects and median E/e' was 9.87 [6.43–13.14]. At rest, biventricular filling pressures were relatively normal, with upper limit mean Pulmonary Pressure (Table). Patients exercised for 6.4 (95% CI: 5.6–7.2) min, achieving a respiratory exchange ratio of 1.11 (1.02–1.17). All subjects displayed normal cardiac output at rest (5.6 L/min (3.7–7.5)), that increased during exertion, due mostly to a rise in heart rate (p<0.0001). Exercise doubled LV End-Diastolic Pressure from 15.3 (11.5–19.1) mmHg at baseline to 30.4 (26.6–34.3) mmHg at peak VO2 (p<0.0001), whereas mean pulmonary pressure increased from 21 (14–29) mmHg to 40 (33–47) mmHg (p<0.0001). Remarkably, although arterial hemodynamics were relatively normal at baseline, exercise induced significant increases both in the continuous (systemic vascular resistance) and pulsatile components of vascular load (Impedances, p<0.05; Table 1) (Figure 1). This increase in afterload during exertion has not been previously documented in HCM. The decreased compliance derived, can also play a role in the elevated filling pressures documented on exertion. Conclusion Exercise unmasks adverse hemodynamics in HCM, severely increasing LV filling pressures and showing systemic arterial dysfunction. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III, Spain.