The Frequency and Functional Impact of Overlapping Hypertension on Hypertrophic Cardiomyopathy: A Single‐Center Experience

Abstract

J Clin Hypertens (Greenwich)

Between 1995 and 2005, 196 adults with hypertrophic cardiomyopathy (HCM) were evaluated. Among these, 122 (62%, group 1) patients also had systemic hypertension. The clinical presentation, management, outcome, and echocardiographic findings of these patients were compared with 74 (38%, group 2) patients without systemic hypertension. Patients in group 1 were older at the time of HCM diagnosis and had a higher prevalence of diabetes (28% vs 9%; P=.02) and coronary artery disease (40% vs 25%; P=.03). In addition, echocardiography showed a significantly higher prevalence of systolic anterior motion of the anterior mitral valve in association with dynamic left ventricular outflow obstruction (52% vs 19%; P=.02) and mitral annular calcification (27% vs 13%; P=.03) in group 1 patients. Left ventricular wall thickness (17 mm vs 19 mm), end‐diastolic diameter (42 mm vs 42 mm), resting outflow tract gradient >30 mm Hg (17% vs 16%), and ejection fraction (65% vs 64%) were similar in the two groups. HCM frequently coexists with systemic hypertension in the adult population. Presence of systemic hypertension in HCM patients is associated with older age and higher risk of diabetes, coronary artery disease, and noncardiac death.

Hypertrophic cardiomyopathy (HCM) is a rare cardiac disease that involves approximately 1 in 500, or 0.2%, of the US population. The heart in this condition is characterized by a hypertrophied nondilated left ventricle with decreased compliance and impaired diastolic relaxation. Features of this disease may also, but not necessarily, include asymmetric hypertrophy, a histological pattern of myocardial fiber disarray, a left ventricular (LV) outflow tract gradient, and systolic anterior motion of mitral valve. Other causes of hypertrophy such as aortic stenosis, hypertension, or myocardial infiltrative diseases such as amyloidosis or glycogen storage disease should be excluded in making this diagnosis. ¹ , ²

Systemic hypertension and HCM are important causes of LV hypertrophy (LVH). The frequency of coexistence of HCM and hypertension increases with age and poses significant diagnostic and management challenges. ³ , ⁴ It is unclear to what extent one disease affects the cardiac phenotypic expression and clinical outcome of the other. The purpose of this study was to compare the echocardiographic and clinical outcome of patients with HCM and with and without systemic hypertension.

Methods

Patient Data

We reviewed the records of the echocardiographic laboratory at Geisinger Medical Center between January 1995 and June 2005 for the diagnosis of HCM. The criteria for exclusion were poor‐quality echocardiogram and the presence of primary valvular disease or end‐stage renal disease. All patients had an echocardiogram because of some clinical suspicion of cardiac disease.

The diagnosis of HCM was based on current criteria, as primarily nonuniformly hypertrophied heart with a minimum LV wall thickness of 15 mm. In addition to LVH (septum ≥15 mm with a normal‐ to small‐sized cavity), a combination of following variables were present: systolic anterior motion of mitral valve at rest or with provocation with amyl nitrite; presence of gradient in the LV outflow tract by Doppler ultrasound or cardiac catheterization at rest or with provocation, and asymmetry of the interventricular septum. The clinical charts and echocardiographic studies were reviewed for all patients.

After reviewing the clinical data, we identified 122 patients who had HCM and systemic hypertension (group 1) and compared their characteristics with 74 patients with HCM alone (group 2).

Clinical Data

Data was collected from chart reviews and electronic medical records. Functional class was based on New York Heart Association classification (I–IV). Systemic hypertension was defined as blood pressure ≥140/90 mm Hg on ≥2 occasions.

Echocardiographic Data

Echocardiographic studies were performed with the use of either a Hewlett‐Packard instrument (Hewlett‐Packard, Palo Alto, CA) with a 2.5/1.9‐MHz transducer or Philips instrument (Philips, Amsterdam, Netherlands) with a 3.5/2.0‐MHz transducer. All images were recorded on VHS video tape recorders. Tapes were reviewed on a Philips editing controller system. Echocardiograms that were technically inadequate for detailed analysis were discarded from the study. The following variables were identified as features for analysis during formal prospective evaluation of echocardiograms.

• • Symmetry or asymmetry was determined by using both M‐mode and 2‐dimensional echocardiography. Wall thickness was obtained from the M‐mode recording according to American Society of Echocardiography recommendations for measurement of the septum and posterior wall of the left ventricle.
• • Systolic anterior motion of mitral valve was recognized with M‐mode and 2‐dimensional echocardiography when the displacement of anterior or posterior leaflets or both toward the septum in systole was observed with or without amyl nitrite provocation.
• • Mitral annular calcification was looked for and described as an increase in echocardiographic density of the annulus in the parasternal long‐axis, short‐axis, and 4‐chamber views.
• • LV outflow tract gradient was measured by continuous wave Doppler echocardiography or at the time of cardiac catheterization. The Doppler measurements were made in m/s and then converted to mm Hg with the use of the simplified Bernoulli equation (P=4V ², where P=pressure gradient and V=velocity of jet).

Statistical Analysis

A Student t test was used to compare mean values between groups. Associations for contingency table data were tested using the chi‐square statistic when appropriate. For tables with small expected cell frequencies, exact tests (Fisher exact or an exact chi‐square) were used. P values <.01 were considered to be statistically significant.

Results

Clinical Findings

One hundred and ninety‐six patients were evaluated at Geisinger Medical Center between January 1995 and June 2005 and diagnosed as having HCM. Of these, 122 patients with both HCM and systemic hypertension (group 1) were identified (Table I). They ranged in age from 44 to 84 years (mean 65±13 years); 86% were 50 years and older. The remaining 74 patients with the diagnosis of HCM without systemic hypertension (group 2) were significantly younger (49.7±18 years). Sixty six (54%) patients in group 1 were men. The duration of hypertension ranged from 3 to 40 years (mean 11±9 years) in the 83 (68%) patients in whom it was known. These 83 patients had an average blood pressure of 175.6±28 mm Hg (systolic) and 93±17 mm Hg (diastolic). All patients had their blood pressure controlled with medications. Family history of HCM was present in 2 (1%) patients in group 1 and 8 (11%) patients in group 2. Cardiac symptoms, murmur, functional heart failure class, and electrocardiographic abnormalities were identical in the two groups.

Table I.

 Patient Demographics

Variable	Hypertensive (n=122)	Nonhypertensive (n=74)	P Value a
Age, y (mean)	44–84 (65±13)	22–69 (49.7±18)
Men, No. (%)	66 (54)	40 (54)	.99
Family history of HCM, No. (%)
Yes	2 (1)	8 (11)
No	8 (6)	7 (9)
Not available	112 (93)	55 (74)
Syncope, No. (%)	10 (8)	9 (12)	.36
Atrial fibrillation, No. (%)	48 (39)	26 (35)	.45
Dyslipidemia, No. (%)	49 (40)	19 (25)	.03
Diabetes, No. (%)	34 (28)	7 (9)	.02
Coronary artery disease, No. (%)	49 (40)	19 (25)	.03
CHF at diagnosis, No. (%)
NYHA class I	72 (59)	25 (34)	.01
NYHA class II	21 (17)	11 (15)	.66
NYHA class III	10 (8)	5 (6)	.7
NYHA class IV	1 (1)	1 (1)
Systolic murmur	72 (59)	45 (61)	.8
Initial presenting symptom, No. (%)
Chest pain	43 (35)	26 (35)	.98
Palpitation	22 (18)	10 (13)	.40
CHF	20 (16)	8 (11)	.27
Murmur	34 (28)	13 (17)	.10
Syncope	11 (9)	4 (5)	.35
Cardiac arrest	0	2 (3)
ECG‐based	0	1
Echo‐based	1	0
Not available	8 (7)	7 (10)

^aSignificance indicated in bold. Abbreviations: CHF, congestive heart failure; ECG, electrocardiography; Echo, echocardiography; HCM, hypertrophic cardiomyopathy; NYHA, New York Heart Association.

Echocardiographic Findings

All 122 patients with HCM and systemic hypertension had septal hypertrophy >15 mm (mean 18±3.8 mm). The mean LV posterior free wall thickness was 13.3±2.5 mm. Mean ejection fraction was 59%±12%. Systolic anterior motion of mitral valve was present in 64 (52%) patients. Mean end‐diastolic diameter was 42.5±6.5 mm and end‐systolic diameter was 23±6.4 mm. The mean left atrial diameter was 42.5±6.5 mm. Mitral annular calcification was present in 42 (35%) patients. A significant LV outflow tract gradient at rest (≥30 mm Hg) and on induction (≥50 mm Hg) was present in 21 (15%) and 19 (15%) patients, respectively. LV outflow tract obstruction was present at rest in 20 (16%) and on induction in 52 (42%) patients.

In the left ventricle, reversal of normal septal curvature was seen in 25 (21%) patients, 8 of whom also had a prominent right ventricular wall, suggesting right ventricular hypertrophy. A normal‐contoured ovoid ventricle was present in the remaining 97 (79%) patients, 70 (72%) of whom also had a proximal septal bulge.

Echocardiographic findings in group 2 patients were similar to those in group 1 patients (Table II). There were no statistically significant differences between the two groups in systolic anterior motion of mitral valve at rest and after provocation, fractional shortening, end‐diastolic diameter, end‐systolic diameter, and left atrial dimension.

Table II.

 Echocardiographic Data

Variable	Hypertensive (n=122)	Nonhypertensive (n=74)	P Value a
Distribution of hypertrophy, No. (%)
Septal	70 (57)	42 (56)	.9
Septal and anterior wall	4 (3)	7 (9)	.06
Septal and apical	2 (2)	0
Apical	9 (7)	3 (4)	.34
Concentric	33 (27)	18 (24)	.67
Not available	5 (4)	4 (5)
Anterior ventricular septum, mm (mean)	17–45 (18±3.8)	18–44 (18.3±3.5)
Posterior wall, mm (mean)	6–28 (13.3±2.5)	6–28 (13.3±2.5)
LV outflow tract obstruction, No. (%)
Resting	20 (16)	14 (19)	.65
Inducible	52 (42)	26 (35)	.29
No	47 (38)	29 (39)	.92
Not available	3 (4)	5 (7)
Significant LV outflow tract gradient, No. (%)
Resting (>30 mm Hg)	21 (17)	12 (16)	.86
Inducible(>50 mm Hg)	19 (9)	7 (9)	.22
Ejection fraction (mean)	25–80 (59±12)	30–75 (62±15)
<35%, No. (%)	4 (3)	6 (8)	.13
35–44%, No. (%)	4 (3)	2 (3)	.82
45–54%, No. (%)	12 (10)	4 (5)	.27
>55%, No. (%)	102 (83)	62 (83)	.9
Left atrial diameter (mean)	25–68 (42.5±6.5)	25–71 (42.4±6.7)
LVED, mm (mean)	25–69 (42.2±6.5)	25–72 (42.4±6.8)
Mitral insufficiency, No. (%)
+1	61 (50)	28 (38)	.09
+2	19 (15)	0
+3	16 (13)	13 (17)	.39
+4	0	1 (2)
Systolic anterior motion	64 (52)	14 (19)	.02

^aSignificance indicated in bold. Abbreviations: LV, left ventricular; LVED, left ventricle at end diastole.

Clinical Follow‐Up Data

Follow‐up data was available in 50 (41%) patients in group 1 and 9 (12%) patients in group 2. Mean follow‐up was 4.6±1.8 years. Common symptoms at the time of clinical presentation are summarized in Table III. Follow‐up events included implantable cardioverter‐defibrillator placement in 4 (3%) patients in group 1 and 9 (12%) patients in group 2; pacemaker placement in 22 (18%) patients in group 1 and 10 (13%) patients in group 2; and cardiac arrest in 1 (0.5%) patient in group 1 and 3 (4%) patients in group 2. There were 39 deaths in group 1 patients (4 due to cardiac cause) and 15 in group 2 (2 due to cardiac cause).

Table III.

 Follow‐Up Data

Variable	Hypertensive (n=122)	Nonhypertensive (n=74)	P Value a
Follow‐up, y (mean)	2–7 (4.5±1.5)	1–10 (4.8±2.3)
Patients with regular follow‐up with cardiologist, No. (%)	50 (41)	9 (12)	.02
Symptoms at last visit, No. (%)
Orthopnea	6 (5)	2 (2)	.44
Exertional dyspnea	47 (38)	18 (24)	.04
Fatigue	18 (15)	12 (16)	.78
Chest pain	9 (7)	2 (2)	.16
Syncope	2 (2)	0
Pre‐syncope	1 (1)	3 (4)
Atrial fibrillation	4 (3)	7 (9)	.06
Congestive heart failure
NYHA class I	32 (26)	18 (24)	.76
NYHA class II	31 (25)	4 (5)	.02
NYHA class III	10 (8)	4 (5)	.4
NYHA class IV	1 (1)	0
Follow‐up events
ICD placement	4 (3)	9 (12)	.01
Pacemaker	22 (18)	10 (13)	.40
Cardiac arrest	1 (1)	3 (4)	.12
Stroke	6 (5)	3 (4)	.78
Death	39 (32)	15 (20)	.07
Cardiac	4 (3)	2 (3)	.8
Noncardiac	30 (25)	11 (14)	.01
Unknown	5 (4)	2 (3)	.01
Age at death, y (mean)	40–96 (68.3)	27–96 (70.2)
Cardiac deaths
CHF	2 (2)	0
Cardiac arrest	1 (1)	1 (1)
Myocardial infarction	0	1 (1)
Sudden cardiac death	1 (1)	0

^aSignificance indicated in bold. Abbreviations: CHF, congestive heart failure; ICD, implantable cardioverter‐defibrillator; NYHA, New York Heart Association.

Management data is summarized in Table IV. There was a statistically significant higher (P>.01) use of calcium channel blockers, diuretics, and warfarin in group 1 patients compared with group 2 patients.

Table IV.

 Management

Variable	Hypertensive (n=122)	Nonhypertensive (n=74)	P Value a
Medical
β‐Blocker, No. (%)	85 (69)	42 (57)	.06
Calcium channel blocker, No. (%)	45 (37)	8 (11)	.02
Amiodarone, No. (%)	12 (10)	5 (7)	.45
Disopyramide, No. (%)	1 (1)	2 (2)
Diuretics, No. (%)	69 (56)	15 (20)	.02
ACE inhibitor/ARB, No. (%)	39 (32)	15 (20)	.07
Warfarin, No. (%)	39 (32)	13 (18)	.02
Surgical myomectomy, No. (%)	10 (8)	8 (11)	.53
ICD, No. (%)	2 (2)	6 (8)	.026
Pacemaker, No. (%)	12 (10)	6 (8)	.68

^aSignificance indicated in bold. Abbreviations: ACE, angiotensin‐converting enzyme; ARB, angiotensin receptor blocker; ICD, implantable cardioverter‐defibrillator.

Discussion

There are inconsistencies in how systemic hypertension is regarded in the setting of HCM. A history of hypertension has been used as an exclusion criterion when making the diagnosis of HCM. ⁵ , ⁶ Some investigators exclude patients with systemic hypertension in their studies, ⁷ unless they believe that the degree of hypertrophy is greater than would be expected in patients with systemic hypertension alone. Exclusion criteria are quite variable and create inconsistencies in our clinical diagnosis and approach to patients with either systemic hypertension or HCM.

Systemic hypertension of mild to moderate degrees sometimes coexist in patients with HCM, predominantly in the elderly. In our study, 122 patients with hypertension in group 1 had a mean age of 65±13 years and were significantly older than the 74 patients with HCM without hypertension studied during the same period. Comparison of these two groups, however, revealed no statistically significant differences in symptoms, functional heart failure class, electrocardiographic changes, LV outflow tract obstruction, and anterior wall thickness. These findings suggest that the cardiac disease of patients who present with HCM with systemic hypertension is indistinguishable from idiopathic HCM and not a distinct condition necessarily related to systemic hypertension. Of particular importance, the patients with systemic hypertension had the same diverse spectrum of disease (including symmetry and asymmetry, obstruction and nonobstruction, and systolic anterior motion) as did those without hypertension.

Topol and colleagues ⁸ described 21 patients with severe concentric hypertrophy and heart failure, 60 years and older, with mild to moderate hypertension. Although they labeled the syndrome “hypertensive hypertrophic cardiomyopathy” to distinguish it from the classic “idiopathic hypertrophic cardiomyopathy” associated with asymmetric hypertrophy, the hypertrophy was more severe than that ordinarily seen with hypertension and they viewed the disease as a part of the spectrum of HCM. A relevant issue raised by Tarazi and Levy ⁹ is that severity of hypertrophy often cannot be related to the severity or duration of hypertension. They suggested that some patients may have a predisposed myocardial sensitivity to development of hypertrophy in the setting of hypertension. Other investigators have clearly shown that only a minority of patients with chronic mild to moderate hypertension develop clinically detectable LVH. ¹⁰ Disease prevalence data also indicate that systemic hypertension does not predictably lead to cardiomyopathy. ¹¹

Hypertension may, however, be a cofactor if not necessarily the cause of cardiac remodeling. In a heart with HCM it might be expected to aggravate the condition by leading to an additional myocardial mass. This is suggested by our study in which hypertensive patients had more free wall hypertrophy than did normotensive patients.

Limitations

A limitation of this study is that it was conducted in a single center, so findings can not be generalized. Also, limited follow‐up data are available, so an appropriate treatment pattern and good blood pressure control was difficult to access.

Conclusions

HCM with systemic hypertension appears to be part of a diverse spectrum of HCM. Although HCM with systemic hypertension is more likely to develop in the elderly, the differences are minimal between HCM in patients with and those without systemic hypertension. Thus, in both young and old patients and in those with or without systemic hypertension, HCM must be explained by factors other than blood pressure. To label this condition “secondary” when systemic hypertension is present at best creates the satisfaction of defining etiology but at worst obscures the real uncertainties as to the cause and relation to other forms of the disease.