Methods

A total of 70 patients with HC were recruited from the HC Center at Tufts Medical Center. The diagnosis of HC was determined using the criteria put forth by the American College of Cardiology/European Society of Cardiology clinical expert consensus document on HC. All patients had LV hypertrophy (wall thickness ≥15 mm according to echocardiographic demonstration) associated with a nondilated cavity in the absence of another cardiac or systemic disease that could produce this magnitude of hypertrophy. The exclusion criteria included severe valvular disease, recent myocardial infarction or unstable cardiac symptoms, peripheral vascular disease, heart failure, end-stage disease with systolic dysfunction or LV ejection fraction <40%, severe arrhythmia, chronic obstructive pulmonary disease, recent exertional syncope, previous septal myectomy, alcohol septal ablation, and coexistent aortic stenosis. Coronary artery disease was defined as the presence of ischemia or infarction on single-photon emission computed tomographic nuclear myocardial perfusion imaging or >50% stenosis of an epicardial coronary artery by angiography. The presence or absence of hypertension (systolic BP/diastolic BP >140/90 mm Hg or taking antihypertensive medication) and clinical symptoms were obtained for each patient from a questionnaire or the medical records. All subjects gave written informed consent, and the institutional review board at Tufts Medical Center approved the present study.

The patients underwent standard 2-dimensional transthoracic echocardiography for assessment of the cardiac dimensions, followed by a symptom-limited exercise test using a standard Bruce protocol with a concurrent hemodynamic assessment. BP was measured using auscultation and sphygmomanometry. The measures at rest were made with the patients with HC in the supine position after a brief quiet rest period. BP was measured thereafter at the end of the exercise stage. An ABPR was defined as a reduction in systolic BP during exercise relative to systolic BP at rest or an inability to increase systolic BP >20 mm Hg during exercise. PP was calculated as systolic BP minus diastolic BP. The patients were instructed to withhold all cardiovascular medications for 24 to 72 hours before exercise testing.

The presence of LV outflow tract obstruction was assessed as previously described at rest, with Valsalva maneuver, and during exercise. LV outflow tract obstruction was defined as a peak instantaneous outflow gradient of ≥30 mm Hg using continuous-wave Doppler echocardiography. Systolic anterior motion and mitral regurgitation were assessed semiquantitatively (scale 0 to 4), as previously described.

All data are reported as the mean ± SEM. A priori significance was set at p <0.05. The normality of distribution was assessed using the Kolmogorov-Smirnof and Shapiro-Wilk tests. Chi-square tests were used to compare the categorical variables. Patients with and without an ABPR were compared using analysis of variance for normally distributed variables and the Mann-Whitney U test for non-normally distributed variables. If the demographic variables differed between the 2 groups, analysis of covariance was used to adjust for the group differences. The patients were then separated into tertiles according to PP, and binary logistic regression analysis was used to examine the predictors of ABPR (entered as a discrete variable).

Results

The baseline demographics are listed in Table 1 . Of the 70 patients, 19 had an ABPR (∼27%). Significant group differences were found in age (p = 0.004) and diuretic use (p = 0.014) between those with and without an ABPR to exercise ( Table 1 ). PP at rest was significantly greater in the patients with HC and an ABPR than in those patients with a normal BP response to exercise (p = 0.007; Table 1 ). The differences in PP remained after adjusting for age and diuretic use with analysis of covariance (adjusted mean 63 mm Hg vs 52 mm Hg, p = 0.028). The differences in PP also remained after adjusting for medication use (adjusted for β blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, Norpace, and other antiarrhythmic agents 64 mm Hg vs 52 mm Hg, p = 0.008). Mean arterial pressure was not significantly different between the 2 groups (p = 0.738; Table 1 ).

The prevalence of ABPR was not different in the patients with HC with versus without LV outflow tract obstruction (30% vs 24%, p = 0.601). PP was not different in the patients with HC who did and did not have LV outflow tract obstruction (56 vs 54 mm Hg, p = 0.612). No gender differences were found in the prevalence of ABPR (men, 26% vs women, 30%, p = 0.776). No gender differences were found in PP (men, 56 ± 3 mm Hg vs women, 51 ± 3, p = 0.264).

When separating the patients into tertiles according to PP, the prevalence of ABPR was significantly greater for the patients with HC with the greatest PP compared to those in the first (reference group) and second tertile (p = 0.008). Of the patients in the greatest tertile (>60 mm Hg), 50% had an ABPR compared to 13% and 17% in the second (range 45 to 60 mm Hg) and third (<45 mm Hg) tertiles, respectively. According to binary logistic regression analysis, after adjusting for potential confounders (age, gender, LV wall thickness, left atrial size, anterior basal septal wall thickness, history of chest pain, history of syncope, family history of HC, LV outflow tract obstruction, coronary artery disease), PP at rest was a significant predictor of the ABPR in patients with HC (p = 0.016). The patients with HC and the greatest PP at rest were 4.8 times more likely to have an ABPR than those with the lowest PP (β = 1.6, Wald = 5.2, 95% confidence interval 1.24 to 18.2, p = 0.023). Systolic BP, diastolic BP, and mean arterial pressure were not significant predictors of ABPR.