- Email: [email protected]
Antihypertensive Therapy in Hypertrophic Cardiomyopathy
Antihypertensive Therapy in Hypertrophic Cardiomyopathy Edgar Argulian, MD, MPH, Franz H. Messerli, MD, Emad F. Aziz, DO, MB, CHB, Glenda Winson, RN, Vikram Agarwal, MD, MPH, Firas Kaddaha, MD, MPH, Bette Kim, MD, and Mark V. Sherrid, MD* Patients with coexisting hypertrophic cardiomyopathy (HC) and hypertension present diagnostic and therapeutic dilemmas. A retrospective cohort study of patients with HC with coexisting hypertension referred to a specialized HC program was conducted. HC and hypertension were confirmed by strict criteria. Echocardiographic data were reviewed for peak instantaneous left ventricular outflow tract gradients, at rest and with provocation. Symptom control, left ventricular outflow tract gradients, and hypertension control were compared between the first and last visits. One hundred fifteen patients (94 obstructed and 21 nonobstructed) met the eligibility criteria for the study and were included in the analysis, with the mean follow-up duration of 36 months. Because of the treatment strategy, there was a significant decrease in the number of patients treated with direct vasodilators and an increase in the use of b blockers and disopyramide. Twenty-one obstructed patients (22%) required septal reduction therapy. Overall, in obstructed patients, peak instantaneous left ventricular outflow tract gradient at rest decreased from 48 to 14 mm Hg (p <0.01), which was accompanied by significant improvement in functional class (2.4 vs 1.8, p <0.01). The prevalence of uncontrolled hypertension decreased from 56% at the initial visit to 37% at the last visit (p [ 0.01). The cohort had a low rate of adverse cardiovascular outcomes such as death, acute coronary syndromes, and stroke. In conclusion, the present study demonstrates that stepwise, symptom-oriented therapy is feasible and effective in patients with coexisting HC and hypertension. Ó 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:1040e1045)
Hypertension is highly prevalent in the general population, and patients with hypertrophic cardiomyopathy (HC) are not exempt from hypertension. At the same time, treatment of patients with HC and hypertension can be challenging. Direct vasodilators such as dihydropyridine calcium channel blockers and renin-angiotensin system blockers (angiotensinconverting enzyme [ACE] inhibitors and angiotensin receptor blockers [ARBs]) are among the most efficacious and welltolerated medications for the treatment of hypertension in general. However, these drugs can exacerbate outflow tract obstruction in patients with HC and may be potentially harmful.1,2 The 2011 American College of Cardiology Foundation and American Heart Association guidelines for the diagnosis and treatment of HC provide little guidance for antihypertensive therapy in patients affected by both conditions.1 In the present retrospective study, we analyzed the efficacy and safety of antihypertensive therapy in patients with HC as practiced at the St. Luke’s-Roosevelt Hospital Center (SLRHC) HC program in New York. Methods We conducted a retrospective cohort study of patients with HC with coexisting hypertension referred to the Hypertrophic Cardiomyopathy Program, Division of Cardiology, St. Luke’s-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, New York. Manuscript received September 10, 2012; revised manuscript received and accepted December 5, 2012. See page 1044 for disclosure information. *Corresponding author: Tel: 212-523-7372; fax: 212-523-7765. E-mail address: [email protected] (M.V. Sherrid). 0002-9149/13/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2012.12.026
SLRHC HC program from January 1995 to January 2011. Patients were referred for confirmation of diagnosis and treatment recommendations. Criteria for diagnosis of HC in this study were echocardiographic demonstration of a hypertrophied nondilated left ventricle 15 mm inappropriate for the degree of hypertension severity and only if 1 of the following 3 criteria were present: (1) dynamic left ventricular (LV) outflow tract (LVOT) obstruction due to systolic anterior motion of the mitral valve and mitral-septal contact at rest or with physiologic provocation, (2) echocardiographic abnormalities typical of HC and generally not seen in hypertensive heart disease (i.e., apical or apical-mid hypertrophy sparing the base, marked asymmetric hypertrophy with systolic anterior motion but with gradients <30 mm Hg, or severe asymmetric hypertrophy with mild hypertension),1,3e5 and (3) in patients with nonobstructive HC, ancillary supportive criteria were a family history of HC in a first-degree family member or genotype analysis showing an HC-related sarcomeric protein mutation. Hypertension was diagnosed conservatively only if 1 or both of the following criteria were present at the initial evaluation: (1) the patient was being actively treated for an established diagnosis of hypertension with a vasodilator such as a dihydropyridine calcium channel blocker, an ACE inhibitor, or an ARB; a thiazide-type diuretic; or clonidine, and (2) the patient had elevated blood pressure readings, defined as systolic pressure 140 mm Hg and/or diastolic pressure 90 mm Hg, on 2 consecutive SLRHC clinic visits. Demographic, clinical, and laboratory data were obtained by retrospective chart review. Blood pressure readings and medications were compared between the initial and the last visits. The study was approved by the institutional review board of St. Luke’s Roosevelt Hospital. www.ajconline.org
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Figure 1. General approach to patients with symptomatic HC and hypertension. AV ¼ atrioventricular; CCB ¼ calcium channel blocker.
Maximal LV wall thickness was measured from parasternal long-axis and short-axis views on 2-dimensional echocardiography, as previously described.6 The initial and follow-up echocardiograms were specifically assessed for systolic anterior motion of the mitral valve and peak instantaneous LVOT gradients. The simplified Bernoulli equation was used to calculate LVOT gradient, and the highest instantaneous gradient was reported.7 Care was taken to separate LVOT signal from that of mitral regurgitation. In all patients, the LVOT gradient was measured in the supine left lateral decubitus position and during 3 separate Valsalva maneuvers and after standing, as previously reported.8 All patients capable of exercising underwent treadmill testing with the Bruce protocol and had gradients acquired after exercise. Patients were excluded from exercise if they had orthopedic disabilities or such severe heart failure symptoms that they were deemed incapable of performing even a modified, reduced treadmill protocol, or for rest gradients >80 mm Hg. Beta blockers were held the morning of the stress test, while other medications were continued. Postestress exercise continuouswave Doppler gradients from the apical views were acquired in the supine left lateral decubitus position within 30e60 seconds after the completion of exercise and then again 3 minutes later.9e11 Patients were deemed to be obstructed if
the maximal peak instantaneous LVOT gradient (at rest or provoked, including postexercise) was 30 mm Hg. Patients with follow-up durations <30 days as well as those without follow-up echocardiographic data were excluded. Patients were also excluded if they had severe mitral regurgitation thought to be unrelated to systolic anterior motion, or severe aortic stenosis. Patients underwent formal stratification for sudden death risk and implantation of implantable cardioverter-defibrillators if, after consideration, the benefits of implantation appeared to outweigh the risks.1 In patients with symptomatic obstructive HC, the initial treatment consisted of discontinuation of vasodilators (if the patient was taking a vasodilator) and administration of maximal tolerated doses of b blockers, nondihydropyridine calcium channel blockers, or both (Figure 1). Beta blockade was the first-line therapy. In patients in whom hypertension was the main current problem, verapamil or diltiazem was started as needed and as heart rate permitted.1,12 If symptoms and elevated gradients persisted after b blockade or nondihydropyridine calcium channel blockade, controlled-release disopyramide was generally added as previously reported.13e16 A combination of all 3 agents was generally avoided unless the patient had a permanent pacemaker. Patients with symptoms refractory to pharmacologic management and rest or provoked gradients
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Table 1 Baseline characteristics Variable
Age (yrs) Men Caucasian Syncope Dyspnea Angina Diabetes mellitus Coronary artery disease Percutaneous coronary intervention Coronary bypass grafting Congestive heart failure Valve surgery Atrial fibrillation More than mild mitral regurgitation More than mild aortic regurgitation More than mild aortic stenosis Implanted device Septal myectomy Alcohol septal ablation Septal thickness (mm)
Overall (n ¼ 115)
60.0 11.7 67 (58%) 93 (81%) 16 (14%) 86 (75%) 42 (37%) 15 (13%) 22 (19%) 11 (10%) 3 (3%) 12 (10%) 3 (3%) 26 (23%) 21 (18%) 5 (4%) 2 (2%) 5 (4%) 2 (2%) 2 (2%) 19.5 4.4
LVOT Obstruction Yes (n ¼ 94)
No (n ¼ 21)
60.2 11.6 54 (58%) 77 (82%) 14 (15%) 77 (82%) 36 (38%) 11 (12%) 21 (22%) 10 (11%) 3 (3%) 12 (13%) 3 (3%) 20 (21%) 20 (21%) 4 (4%) 2 (2%) 3 (3%) 1 (1%) 1 (1%) 19.7 4.4
59.2 12.5 13 (62%) 16 (76%) 2 (10%) 9 (43%) 6 (29%) 4 (19%) 1 (5%) 1 (5%) 0 0 0 6 (29%) 1 (5%) 1 (5%) 0 2 (10%) 1 (5%) 1 (5%) 19.0 4.4
p Value*
0.73 0.71 0.55 0.52 <0.01 0.40 0.37 0.07 0.69 — — — 0.47 0.12 1.0 — 0.23 0.33 0.33 0.51
Data are expressed as mean SD or as number (percentage). * Comparing obstructed to nonobstructed patients.
>50 mm Hg were referred for surgical myectomy. Alcohol septal ablation was reserved for patients with medical contraindications for surgery.1,17 DDD pacing with short atrioventricular delay and complete ventricular capture was applied selectively in specific conditions: (1) in elderly patients who failed pharmacologic therapy and who were deemed to not be good candidates for any other intervention, (2) when an implantable cardioverter-defibrillator was implanted for sudden death prevention in an obstructed patient with mild to moderate heart failure symptoms or syncope, and (3) for symptomatic bradycardia.1 In patients with persistent hypertension after the initial therapy as outlined, clonidine 0.1 mg once or twice daily was given. In patients with refractory hypertension, 12.5 mg (preferred) to 25 mg hydrochlorothiazide was continued or added, generally in association with triamterene. We first assessed the reduction of LVOT gradient at rest and HC-related symptoms. Because many patients did not undergo repeat exercise testing for gradient provocation because symptoms diminished, we did not compare provoked LVOT gradients before and after treatment. Second, we examined the prevalence of hypertension control, defined as systolic pressure <140 mm Hg and diastolic pressure <90 mm Hg at the last visit, and compared blood pressure on the first visit and last visit. Symptoms were assessed by New York Heart Association functional class. Clinical outcomes included all-cause mortality, stroke, new-onset atrial fibrillation, acute coronary syndromes, and congestive heart failure hospitalizations. Means and proportions are reported for the initial and follow-up visits. Continuous variables are reported as mean SD. Means were compared using Student’s t tests, and proportions were compared using chi-square tests and
Fisher’s exact tests. Primary and secondary outcomes were analyzed separately for obstructed and nonobstructed patients. For that purpose, 2-sided paired Student’s t tests and Wilcoxon’s tests were used to compare 2 means, and McNemar’s tests were used to compare proportions. All analyses were performed using commercially available statistical software (SPSS for Windows version 16.0; SPSS, Inc., Chicago, Illinois). Results In this time period, 755 patients with HC had initial evaluation at SLRHC. One hundred fifteen patients (mean age 60 years, 58% men) met the eligibility criteria for the study and were included in the analysis, with a mean follow-up period of 36 32 months (range 1 to 192). Patients with hypertension were older than the rest of the SLRHC cohort without hypertension (mean age 60 vs 53 years, p <0.01). The baseline characteristics for the entire cohort (115 patients) and separately for the obstructed (94 patients, mean rest gradient 48 mm Hg, provoked gradient 112 mm Hg) and nonobstructed (21 patients) groups are listed in Table 1. Overall, patients carried a high burden of symptoms, the most common being dyspnea (75%). Sixty-two patients (54%) had hypertension (blood pressure 140/90 mm Hg) at the initial evaluation. Results are divided into obstructed and nonobstructed patient groups. Because of our treatment strategy, there was a significant decrease in the number of patients treated with peripheral vasodilators such as ACE inhibitors or ARBs (42% vs 14%, p <0.01) and dihydropyridine calcium channel blockers (13% vs 4%, p ¼ 0.03). More patients were treated with
Cardiomyopathy/Hypertension in Hypertrophic Cardiomyopathy Table 2 Changes between the first and the last visits in obstructed patients (n ¼ 94) Variable
Initial Visit
Last Visit
p Value
Hypertensive Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Heart rate (beats/min) Rest LVOT gradient (mm Hg) Provoked LVOT gradient (mm Hg) New York Heart Association class b blockers Increase in dose Verapamil Diltiazem ACE inhibitors/ARBs Dihydropyridine calcium channel blockers Thiazide diuretics Disopyramide Loop diuretics Clonidine
53 (56%) 137 21* 80 11* 65 12 48 49 112 53† 2.4 0.8 58 (62%)
35 (37%) 131 16 77 8 62 11 14 26
0.01 0.01 0.05 0.03 <0.01 <0.01 <0.01 0.13 0.21 <0.01 0.03 0.66 <0.01 0.74 0.02
22 6 39 12
(23%) (6%) (42%) (13%)
1.8 0.7 81 (86%) 44 (76%) 15 (16%) 10 (11%) 13 (14%) 4 (4%)
18 8 7 3
(19%) (9%) (8%) (3%)
16 33 8 10
(17%) (35%) (9%) (11%)
Data are expressed as mean SD or as number (percentage). * Forty-two percent of patients with obstructive HC with hypertension were taking ACE inhibitors or ARBs and 13% were taking dihydropyridine calcium channel blockers at initial evaluation. † Many patients did not exercise again at follow-up if symptomatic relief was obtained.
b blockers (62% vs 86%, p <0.01) at the last visit compared to the initial visit, and the doses were increased in 76% of patients who were taking b blockers at the initial evaluation (Table 2). Disopyramide therapy was increased from 9% to 35% of patients. Despite optimal pharmacologic management, 21 obstructed patients (22%) required septal reduction therapy for symptoms and resistant gradients (surgical myectomy in 19 and alcohol septal ablation in 2). In 15 patients (16%), DDD pacing was used for gradient reduction. With treatment that included septal reduction therapy in selected patients as outlined previously, peak instantaneous LVOT gradient at rest decreased from 48 to 14 mm Hg (p <0.01). Among obstructed patients who did not undergo septal reduction therapy (n ¼ 73), peak instantaneous LVOT gradient at rest decreased from 41 to 18 mm Hg (p <0.01). Overall, the patients experienced a significant reduction in symptom burden during the follow-up period, as assessed by New York Heart Association class (2.4 vs 1.8, p <0.01). The use of clonidine increased from 3% to 11% (p ¼ 0.02). The proportion of patients taking low-dose thiazide diuretics remained similar at 19% and 17% respectively. Despite our stopping peripheral vasodilators such as ACE inhibitors or ARBs and dihydropyridine calcium channel blockers, the average systolic pressure decreased from 137 to 131 mm Hg (p ¼ 0.01). The prevalence of uncontrolled hypertension decreased from 53 (56%) at the initial visit to 35 (37%) at the last visit (p ¼ 0.01; Table 2). Twenty-one patients with HC had maximal provoked instantaneous LVOT gradients <30 mm Hg on therapy at initial evaluation (the nonobstructed group). In this group,
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Table 3 Changes between the first and the last visits in nonobstructed patients (n ¼ 21) Variable
Initial Visit
Last Visit
p Value
Hypertensive Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Heart rate (beats/min) New York Heart Association class Beta blockers Increase in dose Verapamil Diltiazem ACE inhibitors/ARBs Dihydropyridine calcium channel blockers Thiazide diuretics Loop diuretics Clonidine
9 (43%) 130 17* 78 11* 65 9 1.8 0.6 12 (57%)
0.26 0.13 0.12 0.41 0.03 0.66
(19%) (10%) (52%) (10%)
6 (29%) 124 17 75 9 67 10 1.5 0.7 13 (62%) 7 (58%) 6 (29%) 2 (10%) 7 (33%) 4 (19%)
0.41 1.00 0.10 0.16
4 (19%) 5 (24%) 0
3 (14%) 3 (14%) 0
0.66 0.16 —
4 2 11 2
Data are expressed as mean SD or as number (percentage). * Fifty-two percent of patients with nonobstructive HC with hypertension were taking ACE inhibitors or ARBs and 10% were taking dihydropyridine calcium channel blockers at initial evaluation.
19 patients (90%) had patterns of LV hypertrophy typical of HC and not generally seen in hypertensive heart disease with mild elevation of blood pressure. These were apical or apical-mid HC sparing the base in 5 (24%), asymmetric septal hypertrophy with systolic anterior motion but provoked LVOT gradients <30 mm Hg in 3 (14%), and marked asymmetric thickening of the left ventricle disproportionate to the degree of hypertension in 11 (52%).5 Two patients (10%) had septal reduction therapy before initial evaluation: 1 patient had septal myectomy and 1 patient had alcohol septal ablation. In 8 patients (38%), the diagnosis was supported by positive family history and/or gene mutation characteristic of HC. Symptoms were less troubling in the nonobstructed group compared to the obstructed patients: New York Heart Association class 1.8 versus 2.4 (p <0.01) and prevalence of dyspnea 43% versus 82% (p <0.01). Eleven patients (52%) were taking direct vasodilators, and 4 (19%) were taking thiazide diuretics at initial evaluation. With this pharmacotherapy, in the nonobstructed patients, 9 (43%) had hypertension at initial evaluation (Table 3). Beta blocker and calcium channel blocker therapy was optimized in these patients for blood pressure and symptom control. The symptoms mildly diminished (New York Heart Association class 1.8 vs 1.5, p ¼ 0.03), and the prevalence of hypertension trended lower (43% vs 29%, p ¼ 0.26) at the last visit compared to the initial evaluation. During the mean follow-up period of 36 months, only 1 patient died from a noncardiovascular cause (small bowel obstruction). Six patients were newly diagnosed with atrial fibrillation. One patient sustained a stroke, 1 patient had an acute coronary syndrome, and 2 patients were hospitalized for acute decompensated heart failure. There was no deterioration in renal function in any patient due to withdrawal of an ACE inhibitor or ARB over the average 3-year followup period. Nineteen patients (17%) had implantable cardioverter-defibrillators inserted for sudden cardiac death
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prevention. There were 2 appropriate and no inappropriate discharges during the follow-up period. Discussion Patients with HC and systemic hypertension present clinicians with challenging therapeutic and diagnostic dilemmas. Consultants will frequently be referred symptomatic patients with HC who are already taking potent vasodilators, as were half the patients in this series. Although vasodilators are the most effective and welltolerated agents for the treatment of hypertension, in patients with HC, obstructed and nonobstructed, these drugs can be harmful.1,18 In obstructed patients, vasodilators may provoke heart failure symptoms, angina, or syncope by decreasing preload and afterload and increasing LVOT obstruction.1,2,8 In certain nonobstructed patients, particularly those with small LV diastolic chambers, decreasing preload can decrease stroke volume and cause symptoms.3,18 However, in patients with nonobstructive HC without extreme encroachment of the LV cavity, vasodilators have traditionally been used without adverse effects. Hypertension control in this study was modest but was better than the national average of approximately 50%.19 Of note, the evidence for treating complex patients with HC with coexisting hypertension, focusing on symptom control and hypertension control, and long-term outcomes, is extremely scarce. A hypertension treatment strategy as described in this report can provide a framework for management of patients with HC and coexisting hypertension (Figure 1). Symptom control, which is often the reason for specialist referral, is prioritized in obstructed patients. It may be achieved by vasodilator discontinuation and up-titration of a b blocker or verapamil as tolerated. Disopyramide is added in selected symptomatic patients for gradient reduction when symptoms persist despite b blockers or verapamil. If optimal pharmacologic therapy fails and rest or provoked gradients are 50 mm Hg, septal reduction therapy leads to the abolition of gradients and symptomatic improvement. In patients with persistent hypertension despite optimal symptom-control therapy, oral clonidine or a low-dose thiazide diuretic (12.5 to 25 mg of hydrochlorothiazide with triamterene) can assist in blood pressure control. Clonidine suppresses central sympathetic activity and as such may not increase LVOT gradients. Low-dose thiazide can usually only be used with potent concomitant negative inotropic therapy (i.e., disopyramide). We underscore that the strategy we used led not only to significant symptom reduction but also better hypertension control despite discontinuation of vasodilators in most patients. The long-term outcomes were favorable, with low mortality and a low incidence of adverse cardiovascular events. We advance two hypotheses relevant to the concurrence of HC and hypertension. First, hypertension is exceedingly common in the United States population, with an estimated prevalence close to 30% in the adult population, while HC has a prevalence of 0.2% (1 in 500) in the general population.19,20 By coincidence alone, one might expect that close to 1/3 of patients with HC may have hypertension. Several arguments support this. First, our hypertensive
patients with HC were older than normotensive patients with HC and presented for evaluation at a mean age of 60 years, congruent with the increased prevalence of hypertension in older patients. Also, recent data from the Framingham study have shown that in the general population, asymptomatic patients with mild hypertension and LV hypertrophy may have HC-associated sarcomeric protein mutations.21 A second hypothesis is that the systolic hypertension observed in our patients could have originated from the rapid ejection of blood very early in systole, before LV obstruction occurs. Maron et al22 found that 75% of the LV forward flow velocity was ejected in the first third of systole, compared to 37% of forward flow velocity in normal patientss.21 Others have observed rapid early volumetric flow on pulse Doppler23 and with cine angiography. This front-loading of LV ejection may temporally overwhelm the compliance of the large arteries of older patients. Thus, there may be a LV hemodynamic component of hypertension in these patients. This hypothesis has potential therapeutic implications, because potent negative inotropic therapy decreases rapid LV ejection in early systole.24 We believe that the 2 mechanisms for hypertension occur in patients with HC to a varying degree; the latter may be detected by pulsed Doppler echocardiographic interrogation of LV ejection velocities at the entrance of the LVOT upstream of the mitral valve24 and in the aorta.22 Limitations of the present study include its observational nature and single-center experience. Besides, hypertension control was assessed during office visits representing singlepoint measurements as opposed to a 24-hour observation, as can be obtained by ambulatory blood pressure monitoring. Indeed, we used 24-hour blood pressure monitoring for selected patients with labile or white-coat hypertension in whom the adequacy of blood pressure control was an ongoing clinical question. Should all cardiac medications have been stopped several days before the initial evaluation to confirm the diagnosis of hypertension or obstruction? We considered this approach but did not pursue it for three reasons. First, we hoped to correlate the patient’s current symptoms with the current LVOT gradient. We hoped to understand the cause of current symptoms because gradient reduction is the best strategy for symptom reduction. Second, stopping medications may lead to unacceptable blood pressure elevation that precludes exercise testing. This is especially true when b blockers are held for several days. Third, although holding vasodilators might have improved gradients, we view vasodilator-induced obstruction to be another form of provocation. In conclusion, the present study demonstrates that stepwise, symptom-oriented therapy is feasible and effective in patients with coexisting HC and hypertension. Disclosures The authors have no conflicts of interest to disclose. 1. Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE, Towbin JA, Udelson JE, Yancy CW. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in
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collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2011;58:e212ee260. Kyriakidis M, Triposkiadis F, Dernellis J, Androulakis AE, Mellas P, Kelepeshis GA, Gialafos JE. Effects of cardiac versus circulatory angiotensin-converting enzyme inhibition on left ventricular diastolic function and coronary blood flow in hypertrophic obstructive cardiomyopathy. Circulation 1998;97:1342e1347. Shah A, Duncan K, Winson G, Chaudhry FA, Sherrid MV. Severe symptoms in mid and apical hypertrophic cardiomyopathy. Echocardiography 2009;26:922e933. Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002;287:1308e1320. Lewis JF, Maron BJ. Diversity of patterns of hypertrophy in patients with systemic hypertension and marked left ventricular wall thickening. Am J Cardiol 1990;65:874e881. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000;342: 1778e1785. Sasson Z, Yock PG, Hatle LK, Alderman EL, Popp RL. Doppler echocardiographic determination of the pressure gradient in hypertrophic cardiomyopathy. J Am Coll Cardiol 1988;11:752e756. Joshi S, Patel UK, Yao SS, Castenada V, Isambert A, Winson G, Chaudhry FA, Sherrid MV. Standing and exercise Doppler echocardiography in obstructive hypertrophic cardiomyopathy: the range of gradients with upright activity. J Am Soc Echocardiogr 2011;24: 75e82. Klues HG, Leuner C, Kuhn H. Left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: increase in gradient after exercise. J Am Coll Cardiol 1992;19:527e533. Maron MS, Olivotto I, Zenovich AG, Link MS, Pandian NG, Kuvin JT, Nistri S, Cecchi F, Udelson JE, Maron BJ. Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation 2006;114:2232e2239. Drinko JK, Nash PJ, Lever HM, Asher CR. Safety of stress testing in patients with hypertrophic cardiomyopathy. Am J Cardiol 2004;93: 1443e1444. Epstein SE, Rosing DR. Verapamil: its potential for causing serious complications in patients with hypertrophic cardiomyopathy. Circulation 1981;64:437e441.
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13. Sherrid MV, Barac I, McKenna WJ, Elliott PM, Dickie S, Chojnowska L, Casey S, Maron BJ. Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2005;45:1251e1258. 14. Wigle ED, Rakowski H, Kimball BP, Williams WG. Hypertrophic cardiomyopathy. Clinical spectrum and treatment. Circulation 1995;92:1680e1692. 15. Fifer MA, Vlahakes GJ. Management of symptoms in hypertrophic cardiomyopathy. Circulation 2008;117:429e439. 16. Sherrid MV, Arabadjian M. A primer of disopyramide treatment of obstructive hypertrophic cardiomyopathy. Prog Cardiovasc Dis 2012;54:483e492. 17. Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, Shah PM, Spencer WH III, Spirito P, Ten Cate FJ, Wigle ED. American College of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol 2003;42:1687e1713. 18. Topol EJ, Traill TA, Fortuin NJ. Hypertensive hypertrophic cardiomyopathy of the elderly. N Engl J Med 1985;312:277e283. 19. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment, and control of hypertension 1988e2008. JAMA 2010;303: 2043e2050. 20. Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Circulation 1995;92:785e789. 21. Morita H, Larson MG, Barr SC, Vasan RS, O’Donnell CJ, Hirschhorn JN, Levy D, Corey D, Seidman CE, Seidman JG, Benjamin EJ. Singlegene mutations and increased left ventricular wall thickness in the community: the Framingham Heart Study. Circulation 2006;113: 2697e2705. 22. Maron BJ, Gottdiener JS, Arce J, Rosing DR, Wesley YE, Epstein SE. Dynamic subaortic obstruction in hypertrophic cardiomyopathy: analysis by pulsed Doppler echocardiography. J Am Coll Cardiol 1985;6:1e18. 23. Conklin HM, Huang X, Davies CH, Sahn DJ, Shively BK. Biphasic left ventricular outflow and its mechanism in hypertrophic obstructive cardiomyopathy. J Am Soc Echocardiogr 2004;17:375e383. 24. Sherrid MV, Pearle G, Gunsburg DZ. Mechanism of benefit of negative inotropes in obstructive hypertrophic cardiomyopathy. Circulation 1998;97:41e47.
Hypertension is highly prevalent in the general population, and patients with hypertrophic cardiomyopathy (HC) are not exempt from hypertension. At the same time, treatment of patients with HC and hypertension can be challenging. Direct vasodilators such as dihydropyridine calcium channel blockers and renin-angiotensin system blockers (angiotensinconverting enzyme [ACE] inhibitors and angiotensin receptor blockers [ARBs]) are among the most efficacious and welltolerated medications for the treatment of hypertension in general. However, these drugs can exacerbate outflow tract obstruction in patients with HC and may be potentially harmful.1,2 The 2011 American College of Cardiology Foundation and American Heart Association guidelines for the diagnosis and treatment of HC provide little guidance for antihypertensive therapy in patients affected by both conditions.1 In the present retrospective study, we analyzed the efficacy and safety of antihypertensive therapy in patients with HC as practiced at the St. Luke’s-Roosevelt Hospital Center (SLRHC) HC program in New York. Methods We conducted a retrospective cohort study of patients with HC with coexisting hypertension referred to the Hypertrophic Cardiomyopathy Program, Division of Cardiology, St. Luke’s-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, New York. Manuscript received September 10, 2012; revised manuscript received and accepted December 5, 2012. See page 1044 for disclosure information. *Corresponding author: Tel: 212-523-7372; fax: 212-523-7765. E-mail address: [email protected] (M.V. Sherrid). 0002-9149/13/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2012.12.026
SLRHC HC program from January 1995 to January 2011. Patients were referred for confirmation of diagnosis and treatment recommendations. Criteria for diagnosis of HC in this study were echocardiographic demonstration of a hypertrophied nondilated left ventricle 15 mm inappropriate for the degree of hypertension severity and only if 1 of the following 3 criteria were present: (1) dynamic left ventricular (LV) outflow tract (LVOT) obstruction due to systolic anterior motion of the mitral valve and mitral-septal contact at rest or with physiologic provocation, (2) echocardiographic abnormalities typical of HC and generally not seen in hypertensive heart disease (i.e., apical or apical-mid hypertrophy sparing the base, marked asymmetric hypertrophy with systolic anterior motion but with gradients <30 mm Hg, or severe asymmetric hypertrophy with mild hypertension),1,3e5 and (3) in patients with nonobstructive HC, ancillary supportive criteria were a family history of HC in a first-degree family member or genotype analysis showing an HC-related sarcomeric protein mutation. Hypertension was diagnosed conservatively only if 1 or both of the following criteria were present at the initial evaluation: (1) the patient was being actively treated for an established diagnosis of hypertension with a vasodilator such as a dihydropyridine calcium channel blocker, an ACE inhibitor, or an ARB; a thiazide-type diuretic; or clonidine, and (2) the patient had elevated blood pressure readings, defined as systolic pressure 140 mm Hg and/or diastolic pressure 90 mm Hg, on 2 consecutive SLRHC clinic visits. Demographic, clinical, and laboratory data were obtained by retrospective chart review. Blood pressure readings and medications were compared between the initial and the last visits. The study was approved by the institutional review board of St. Luke’s Roosevelt Hospital. www.ajconline.org
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Figure 1. General approach to patients with symptomatic HC and hypertension. AV ¼ atrioventricular; CCB ¼ calcium channel blocker.
Maximal LV wall thickness was measured from parasternal long-axis and short-axis views on 2-dimensional echocardiography, as previously described.6 The initial and follow-up echocardiograms were specifically assessed for systolic anterior motion of the mitral valve and peak instantaneous LVOT gradients. The simplified Bernoulli equation was used to calculate LVOT gradient, and the highest instantaneous gradient was reported.7 Care was taken to separate LVOT signal from that of mitral regurgitation. In all patients, the LVOT gradient was measured in the supine left lateral decubitus position and during 3 separate Valsalva maneuvers and after standing, as previously reported.8 All patients capable of exercising underwent treadmill testing with the Bruce protocol and had gradients acquired after exercise. Patients were excluded from exercise if they had orthopedic disabilities or such severe heart failure symptoms that they were deemed incapable of performing even a modified, reduced treadmill protocol, or for rest gradients >80 mm Hg. Beta blockers were held the morning of the stress test, while other medications were continued. Postestress exercise continuouswave Doppler gradients from the apical views were acquired in the supine left lateral decubitus position within 30e60 seconds after the completion of exercise and then again 3 minutes later.9e11 Patients were deemed to be obstructed if
the maximal peak instantaneous LVOT gradient (at rest or provoked, including postexercise) was 30 mm Hg. Patients with follow-up durations <30 days as well as those without follow-up echocardiographic data were excluded. Patients were also excluded if they had severe mitral regurgitation thought to be unrelated to systolic anterior motion, or severe aortic stenosis. Patients underwent formal stratification for sudden death risk and implantation of implantable cardioverter-defibrillators if, after consideration, the benefits of implantation appeared to outweigh the risks.1 In patients with symptomatic obstructive HC, the initial treatment consisted of discontinuation of vasodilators (if the patient was taking a vasodilator) and administration of maximal tolerated doses of b blockers, nondihydropyridine calcium channel blockers, or both (Figure 1). Beta blockade was the first-line therapy. In patients in whom hypertension was the main current problem, verapamil or diltiazem was started as needed and as heart rate permitted.1,12 If symptoms and elevated gradients persisted after b blockade or nondihydropyridine calcium channel blockade, controlled-release disopyramide was generally added as previously reported.13e16 A combination of all 3 agents was generally avoided unless the patient had a permanent pacemaker. Patients with symptoms refractory to pharmacologic management and rest or provoked gradients
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Table 1 Baseline characteristics Variable
Age (yrs) Men Caucasian Syncope Dyspnea Angina Diabetes mellitus Coronary artery disease Percutaneous coronary intervention Coronary bypass grafting Congestive heart failure Valve surgery Atrial fibrillation More than mild mitral regurgitation More than mild aortic regurgitation More than mild aortic stenosis Implanted device Septal myectomy Alcohol septal ablation Septal thickness (mm)
Overall (n ¼ 115)
60.0 11.7 67 (58%) 93 (81%) 16 (14%) 86 (75%) 42 (37%) 15 (13%) 22 (19%) 11 (10%) 3 (3%) 12 (10%) 3 (3%) 26 (23%) 21 (18%) 5 (4%) 2 (2%) 5 (4%) 2 (2%) 2 (2%) 19.5 4.4
LVOT Obstruction Yes (n ¼ 94)
No (n ¼ 21)
60.2 11.6 54 (58%) 77 (82%) 14 (15%) 77 (82%) 36 (38%) 11 (12%) 21 (22%) 10 (11%) 3 (3%) 12 (13%) 3 (3%) 20 (21%) 20 (21%) 4 (4%) 2 (2%) 3 (3%) 1 (1%) 1 (1%) 19.7 4.4
59.2 12.5 13 (62%) 16 (76%) 2 (10%) 9 (43%) 6 (29%) 4 (19%) 1 (5%) 1 (5%) 0 0 0 6 (29%) 1 (5%) 1 (5%) 0 2 (10%) 1 (5%) 1 (5%) 19.0 4.4
p Value*
0.73 0.71 0.55 0.52 <0.01 0.40 0.37 0.07 0.69 — — — 0.47 0.12 1.0 — 0.23 0.33 0.33 0.51
Data are expressed as mean SD or as number (percentage). * Comparing obstructed to nonobstructed patients.
>50 mm Hg were referred for surgical myectomy. Alcohol septal ablation was reserved for patients with medical contraindications for surgery.1,17 DDD pacing with short atrioventricular delay and complete ventricular capture was applied selectively in specific conditions: (1) in elderly patients who failed pharmacologic therapy and who were deemed to not be good candidates for any other intervention, (2) when an implantable cardioverter-defibrillator was implanted for sudden death prevention in an obstructed patient with mild to moderate heart failure symptoms or syncope, and (3) for symptomatic bradycardia.1 In patients with persistent hypertension after the initial therapy as outlined, clonidine 0.1 mg once or twice daily was given. In patients with refractory hypertension, 12.5 mg (preferred) to 25 mg hydrochlorothiazide was continued or added, generally in association with triamterene. We first assessed the reduction of LVOT gradient at rest and HC-related symptoms. Because many patients did not undergo repeat exercise testing for gradient provocation because symptoms diminished, we did not compare provoked LVOT gradients before and after treatment. Second, we examined the prevalence of hypertension control, defined as systolic pressure <140 mm Hg and diastolic pressure <90 mm Hg at the last visit, and compared blood pressure on the first visit and last visit. Symptoms were assessed by New York Heart Association functional class. Clinical outcomes included all-cause mortality, stroke, new-onset atrial fibrillation, acute coronary syndromes, and congestive heart failure hospitalizations. Means and proportions are reported for the initial and follow-up visits. Continuous variables are reported as mean SD. Means were compared using Student’s t tests, and proportions were compared using chi-square tests and
Fisher’s exact tests. Primary and secondary outcomes were analyzed separately for obstructed and nonobstructed patients. For that purpose, 2-sided paired Student’s t tests and Wilcoxon’s tests were used to compare 2 means, and McNemar’s tests were used to compare proportions. All analyses were performed using commercially available statistical software (SPSS for Windows version 16.0; SPSS, Inc., Chicago, Illinois). Results In this time period, 755 patients with HC had initial evaluation at SLRHC. One hundred fifteen patients (mean age 60 years, 58% men) met the eligibility criteria for the study and were included in the analysis, with a mean follow-up period of 36 32 months (range 1 to 192). Patients with hypertension were older than the rest of the SLRHC cohort without hypertension (mean age 60 vs 53 years, p <0.01). The baseline characteristics for the entire cohort (115 patients) and separately for the obstructed (94 patients, mean rest gradient 48 mm Hg, provoked gradient 112 mm Hg) and nonobstructed (21 patients) groups are listed in Table 1. Overall, patients carried a high burden of symptoms, the most common being dyspnea (75%). Sixty-two patients (54%) had hypertension (blood pressure 140/90 mm Hg) at the initial evaluation. Results are divided into obstructed and nonobstructed patient groups. Because of our treatment strategy, there was a significant decrease in the number of patients treated with peripheral vasodilators such as ACE inhibitors or ARBs (42% vs 14%, p <0.01) and dihydropyridine calcium channel blockers (13% vs 4%, p ¼ 0.03). More patients were treated with
Cardiomyopathy/Hypertension in Hypertrophic Cardiomyopathy Table 2 Changes between the first and the last visits in obstructed patients (n ¼ 94) Variable
Initial Visit
Last Visit
p Value
Hypertensive Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Heart rate (beats/min) Rest LVOT gradient (mm Hg) Provoked LVOT gradient (mm Hg) New York Heart Association class b blockers Increase in dose Verapamil Diltiazem ACE inhibitors/ARBs Dihydropyridine calcium channel blockers Thiazide diuretics Disopyramide Loop diuretics Clonidine
53 (56%) 137 21* 80 11* 65 12 48 49 112 53† 2.4 0.8 58 (62%)
35 (37%) 131 16 77 8 62 11 14 26
0.01 0.01 0.05 0.03 <0.01 <0.01 <0.01 0.13 0.21 <0.01 0.03 0.66 <0.01 0.74 0.02
22 6 39 12
(23%) (6%) (42%) (13%)
1.8 0.7 81 (86%) 44 (76%) 15 (16%) 10 (11%) 13 (14%) 4 (4%)
18 8 7 3
(19%) (9%) (8%) (3%)
16 33 8 10
(17%) (35%) (9%) (11%)
Data are expressed as mean SD or as number (percentage). * Forty-two percent of patients with obstructive HC with hypertension were taking ACE inhibitors or ARBs and 13% were taking dihydropyridine calcium channel blockers at initial evaluation. † Many patients did not exercise again at follow-up if symptomatic relief was obtained.
b blockers (62% vs 86%, p <0.01) at the last visit compared to the initial visit, and the doses were increased in 76% of patients who were taking b blockers at the initial evaluation (Table 2). Disopyramide therapy was increased from 9% to 35% of patients. Despite optimal pharmacologic management, 21 obstructed patients (22%) required septal reduction therapy for symptoms and resistant gradients (surgical myectomy in 19 and alcohol septal ablation in 2). In 15 patients (16%), DDD pacing was used for gradient reduction. With treatment that included septal reduction therapy in selected patients as outlined previously, peak instantaneous LVOT gradient at rest decreased from 48 to 14 mm Hg (p <0.01). Among obstructed patients who did not undergo septal reduction therapy (n ¼ 73), peak instantaneous LVOT gradient at rest decreased from 41 to 18 mm Hg (p <0.01). Overall, the patients experienced a significant reduction in symptom burden during the follow-up period, as assessed by New York Heart Association class (2.4 vs 1.8, p <0.01). The use of clonidine increased from 3% to 11% (p ¼ 0.02). The proportion of patients taking low-dose thiazide diuretics remained similar at 19% and 17% respectively. Despite our stopping peripheral vasodilators such as ACE inhibitors or ARBs and dihydropyridine calcium channel blockers, the average systolic pressure decreased from 137 to 131 mm Hg (p ¼ 0.01). The prevalence of uncontrolled hypertension decreased from 53 (56%) at the initial visit to 35 (37%) at the last visit (p ¼ 0.01; Table 2). Twenty-one patients with HC had maximal provoked instantaneous LVOT gradients <30 mm Hg on therapy at initial evaluation (the nonobstructed group). In this group,
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Table 3 Changes between the first and the last visits in nonobstructed patients (n ¼ 21) Variable
Initial Visit
Last Visit
p Value
Hypertensive Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Heart rate (beats/min) New York Heart Association class Beta blockers Increase in dose Verapamil Diltiazem ACE inhibitors/ARBs Dihydropyridine calcium channel blockers Thiazide diuretics Loop diuretics Clonidine
9 (43%) 130 17* 78 11* 65 9 1.8 0.6 12 (57%)
0.26 0.13 0.12 0.41 0.03 0.66
(19%) (10%) (52%) (10%)
6 (29%) 124 17 75 9 67 10 1.5 0.7 13 (62%) 7 (58%) 6 (29%) 2 (10%) 7 (33%) 4 (19%)
0.41 1.00 0.10 0.16
4 (19%) 5 (24%) 0
3 (14%) 3 (14%) 0
0.66 0.16 —
4 2 11 2
Data are expressed as mean SD or as number (percentage). * Fifty-two percent of patients with nonobstructive HC with hypertension were taking ACE inhibitors or ARBs and 10% were taking dihydropyridine calcium channel blockers at initial evaluation.
19 patients (90%) had patterns of LV hypertrophy typical of HC and not generally seen in hypertensive heart disease with mild elevation of blood pressure. These were apical or apical-mid HC sparing the base in 5 (24%), asymmetric septal hypertrophy with systolic anterior motion but provoked LVOT gradients <30 mm Hg in 3 (14%), and marked asymmetric thickening of the left ventricle disproportionate to the degree of hypertension in 11 (52%).5 Two patients (10%) had septal reduction therapy before initial evaluation: 1 patient had septal myectomy and 1 patient had alcohol septal ablation. In 8 patients (38%), the diagnosis was supported by positive family history and/or gene mutation characteristic of HC. Symptoms were less troubling in the nonobstructed group compared to the obstructed patients: New York Heart Association class 1.8 versus 2.4 (p <0.01) and prevalence of dyspnea 43% versus 82% (p <0.01). Eleven patients (52%) were taking direct vasodilators, and 4 (19%) were taking thiazide diuretics at initial evaluation. With this pharmacotherapy, in the nonobstructed patients, 9 (43%) had hypertension at initial evaluation (Table 3). Beta blocker and calcium channel blocker therapy was optimized in these patients for blood pressure and symptom control. The symptoms mildly diminished (New York Heart Association class 1.8 vs 1.5, p ¼ 0.03), and the prevalence of hypertension trended lower (43% vs 29%, p ¼ 0.26) at the last visit compared to the initial evaluation. During the mean follow-up period of 36 months, only 1 patient died from a noncardiovascular cause (small bowel obstruction). Six patients were newly diagnosed with atrial fibrillation. One patient sustained a stroke, 1 patient had an acute coronary syndrome, and 2 patients were hospitalized for acute decompensated heart failure. There was no deterioration in renal function in any patient due to withdrawal of an ACE inhibitor or ARB over the average 3-year followup period. Nineteen patients (17%) had implantable cardioverter-defibrillators inserted for sudden cardiac death
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prevention. There were 2 appropriate and no inappropriate discharges during the follow-up period. Discussion Patients with HC and systemic hypertension present clinicians with challenging therapeutic and diagnostic dilemmas. Consultants will frequently be referred symptomatic patients with HC who are already taking potent vasodilators, as were half the patients in this series. Although vasodilators are the most effective and welltolerated agents for the treatment of hypertension, in patients with HC, obstructed and nonobstructed, these drugs can be harmful.1,18 In obstructed patients, vasodilators may provoke heart failure symptoms, angina, or syncope by decreasing preload and afterload and increasing LVOT obstruction.1,2,8 In certain nonobstructed patients, particularly those with small LV diastolic chambers, decreasing preload can decrease stroke volume and cause symptoms.3,18 However, in patients with nonobstructive HC without extreme encroachment of the LV cavity, vasodilators have traditionally been used without adverse effects. Hypertension control in this study was modest but was better than the national average of approximately 50%.19 Of note, the evidence for treating complex patients with HC with coexisting hypertension, focusing on symptom control and hypertension control, and long-term outcomes, is extremely scarce. A hypertension treatment strategy as described in this report can provide a framework for management of patients with HC and coexisting hypertension (Figure 1). Symptom control, which is often the reason for specialist referral, is prioritized in obstructed patients. It may be achieved by vasodilator discontinuation and up-titration of a b blocker or verapamil as tolerated. Disopyramide is added in selected symptomatic patients for gradient reduction when symptoms persist despite b blockers or verapamil. If optimal pharmacologic therapy fails and rest or provoked gradients are 50 mm Hg, septal reduction therapy leads to the abolition of gradients and symptomatic improvement. In patients with persistent hypertension despite optimal symptom-control therapy, oral clonidine or a low-dose thiazide diuretic (12.5 to 25 mg of hydrochlorothiazide with triamterene) can assist in blood pressure control. Clonidine suppresses central sympathetic activity and as such may not increase LVOT gradients. Low-dose thiazide can usually only be used with potent concomitant negative inotropic therapy (i.e., disopyramide). We underscore that the strategy we used led not only to significant symptom reduction but also better hypertension control despite discontinuation of vasodilators in most patients. The long-term outcomes were favorable, with low mortality and a low incidence of adverse cardiovascular events. We advance two hypotheses relevant to the concurrence of HC and hypertension. First, hypertension is exceedingly common in the United States population, with an estimated prevalence close to 30% in the adult population, while HC has a prevalence of 0.2% (1 in 500) in the general population.19,20 By coincidence alone, one might expect that close to 1/3 of patients with HC may have hypertension. Several arguments support this. First, our hypertensive
patients with HC were older than normotensive patients with HC and presented for evaluation at a mean age of 60 years, congruent with the increased prevalence of hypertension in older patients. Also, recent data from the Framingham study have shown that in the general population, asymptomatic patients with mild hypertension and LV hypertrophy may have HC-associated sarcomeric protein mutations.21 A second hypothesis is that the systolic hypertension observed in our patients could have originated from the rapid ejection of blood very early in systole, before LV obstruction occurs. Maron et al22 found that 75% of the LV forward flow velocity was ejected in the first third of systole, compared to 37% of forward flow velocity in normal patientss.21 Others have observed rapid early volumetric flow on pulse Doppler23 and with cine angiography. This front-loading of LV ejection may temporally overwhelm the compliance of the large arteries of older patients. Thus, there may be a LV hemodynamic component of hypertension in these patients. This hypothesis has potential therapeutic implications, because potent negative inotropic therapy decreases rapid LV ejection in early systole.24 We believe that the 2 mechanisms for hypertension occur in patients with HC to a varying degree; the latter may be detected by pulsed Doppler echocardiographic interrogation of LV ejection velocities at the entrance of the LVOT upstream of the mitral valve24 and in the aorta.22 Limitations of the present study include its observational nature and single-center experience. Besides, hypertension control was assessed during office visits representing singlepoint measurements as opposed to a 24-hour observation, as can be obtained by ambulatory blood pressure monitoring. Indeed, we used 24-hour blood pressure monitoring for selected patients with labile or white-coat hypertension in whom the adequacy of blood pressure control was an ongoing clinical question. Should all cardiac medications have been stopped several days before the initial evaluation to confirm the diagnosis of hypertension or obstruction? We considered this approach but did not pursue it for three reasons. First, we hoped to correlate the patient’s current symptoms with the current LVOT gradient. We hoped to understand the cause of current symptoms because gradient reduction is the best strategy for symptom reduction. Second, stopping medications may lead to unacceptable blood pressure elevation that precludes exercise testing. This is especially true when b blockers are held for several days. Third, although holding vasodilators might have improved gradients, we view vasodilator-induced obstruction to be another form of provocation. In conclusion, the present study demonstrates that stepwise, symptom-oriented therapy is feasible and effective in patients with coexisting HC and hypertension. Disclosures The authors have no conflicts of interest to disclose. 1. Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE, Towbin JA, Udelson JE, Yancy CW. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in
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