Hypertrophic Cardiomyopathy: Prevalence, Hypertrophy Patterns, and Their Clinical and ECG Findings in a Hospital at Qatar.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic disease associated with risk of morbidity and sudden cardiac death. The prevalence, hypertrophy patterns, mode of presentations, and different ECG findings vary in different regions of the world. To date, no data is present regarding these variables in Qatar. PATIENTS AND METHODS: A retrospective, cross sectional, descriptive analysis of all patients referred for echocardiography study at Hamad General Hospital, Qatar. The study period was from January 2008 till December 2010. AIMS: To study 1) the prevalence of HCM, 2) the different patterns of hypertrophy, and 3) the clinical and ECG presentations in this population.
RESULTS: Out of the 29,286 cases evaluated, 38 patients were found to have HCM (0.13%). Their clinical, ECG, and echocardiography findings were analyzed. Mean age was 47 y, 35 males (92%) and 3 females (8%). Four patterns of hypertrophy were described; 17 (44.7%) had septal hypertrophy alone, 6 (15.8%) had septal and other segments hypertrophy but sparing the apex, 10 (26.3%) had apical segments along with any other segment hypertrophy, and 5 (13.2%) had apical hypertrophy alone. No obstruction was found in 19 (50%), left ventricular outflow (LVO) tract obstruction was found in 13 (34%), and mid cavity obstruction (MCO) in 6 (16%). Twenty one (55.3%) patients were referred because of chest pain, 15 (39.5%) with palpitations, 15 (39.5%) with shortness of breath, and 5 (13.2%) with syncope. Nine patients (23.7%) were asymptomatic and were referred because of cardiac murmur during routine examination. ECG evidence of LV hypertrophy was found in 29 (76.3%).
CONCLUSION: The prevalence of HCM in our population group is 0.13% with a male predominance (12:1). There was a diversity of clinical presentation, ECG abnormalities and patterns of LV hypertrophy among HCM patients.

INTRODUCTION

Hypertrophic cardiomyopathy (HCM) is a genetically transmitted disease with broad morphologic and clinical spectrum.[1-4] Patients with hypertrophic cardiomyopathy are mostly discovered during routine examination, because of ECG abnormalities, or when they become symptomatic.[14] Echocardiography remains the corner stone for its diagnosis and classification.[45] Also, HCM appears to have different hypertrophy patterns, clinical and ECG findings.[5] At present, there is no published data on hypertrophic cardiomyopathy in Qatar. Hamad General Hospital (HGH) is a tertiary hospital serving a variety of patients of different nationalities, ethnicity, and socioeconomic strata.

Aims of study

Our aim of work was to study

The prevalence of HCM at HGH echocardiography lab. During the period of January, 2008 till December, 2010;

The demographic characteristics of this population;

The different patterns of hypertrophy;

The presence and level of left ventricular obstruction namely outflow or mid cavity; and

The clinical presentation and electrocardiographic abnormalities in this group.

PATIENTS AND METHODS

This study is a retrospective cross sectional, descriptive study. Echocardiographic data from January 2008 to December 2010 were analyzed. All patients referred for echocardiography during this period were included. Probable or definite echocardiographic evidence of HCM on the basis of identification of a hypertrophied, non dilated left ventricle with inter ventricular septum / posterior wall thickness ≥1.5 and if was not associated with systemic hypertension or other loading conditions as aortic stenosis, coarctation, or structural LVOT obstruction.

Exclusion criteria were:

Non-diagnostic echocardiographic studies;

Incomplete studies;

Other concomitant loading or systemic conditions that may lead to left ventricular hypertrophy; and

Patients with surgical or catheter septal myomectomy.

Echocardiographic data analysis

All echocardiographic studies were performed at HGH by trained echocardiographic cardiac sonographers and were interpreted at the time of study by non invasive cardiologists. Most of these studies were reviewed by senior cardiologists for quality assurance before final reports were produced. All patients with a final diagnosis of hypertrophic cardiomyopathy during the period of January 2008 till December 2010 were included. Thirty-eight patients were selected for further analysis which included: 1) Reviewing the 2D, M-mode and Doppler measurements; 2) Detecting and grading of the systolic anterior motion of the mitral valve, LV outflow tract obstruction, intracavitary obstruction and mitral incompetence; and 3) Describing the pattern of left ventricular hypertrophy.

Left ventricular outflow dynamic obstruction was defined as having a resting gradient ≥ 20 mm Hg at rest and/or ≥ 50 mm Hg with provocation and with no evidence of mechanical obstruction such as sub aortic membrane, aortic valve disease, or coarctation. Characteristic Doppler signal with late peaking was adjunct diagnostic criteria. Provocative tests were such as sublingual nitrates or valsalva maneuver was performed in selected cases. Special attention was taken that outflow signals were not contaminated by mitral incompetence. Spatial diagnosis was confirmed by color flow imaging which showed systolic turbulence commencing at a sub valvular level, and to differentiate it for mitral incompetence. Also, timing of these signals to occur after the isovolumic contraction phase as judged by the closure of the mitral valve and aortic valve opening signals were used as a pre requisite for the diagnosis when both mitral incompetence and LVOT obstruction were associated. Intra or mid cavity gradient was diagnosed when there was a gradient ≥ 30 mm Hg at rest. Color flow imaging was utilized to confirm a mid cavity turbulence in these cases.

ECG analysis

Romhilt - Estes point score system[67] was utilized for semi-quantitative analysis [Table 1]: Romhilt-Estes score was calculated as:- 3 points for any limb lead R or S wave ≥ 2.0 mv (20 mm) or S wave in V1 or V2 ≥ 3mv (30 mm) or R wave in V5 or V6 ≥ 3.0 mv (30 mm); 3 points for secondary ST-T wave changes typical of LVH; 3 points for left atrial abnormality as P terminal force in V1 ≥ 1 mm in depth with a duration of 40 msec; 2 points for left axis deviation ≥ -30°; 1 point for QRS duration ≥ 90 msec; and 1 point for intrinsicoid deflection defined as the interval between beginning of QRS and peak of R-wave in V5 or V6 ≥ 0.05 sec. We considered a score sum of > 5 as definite LV hypertrophy.

Table 1

Romhilt–Estes point score system for ECG diagnosis of LVH

Data collection and analysis

Demographic data such as age, gender, and nationality; clinical presentation; ECG data; and echocardiographic data were described. Microsoft Office® Excel software was used for data entry and IBM SPSS 18 was used for descriptive statistics. Continuous values were described as mean ± SD and categorical values were described in the form of frequency and percentages.

RESULTS

Prevalence

During the period between January 2008 and December 2010, 29,286 patients, 19,572 (66.8%) males and 9,714 (33.2%) females were referred to our echocardiography lab. at HGH. Thirty eight (38) cases (0.13%) [35 males (0.17%) and 3 females (0.03%)] were found to have echocardiography features of hypertrophic cardiomyopathy. Prevalence among Qataris was 0.07%, 0.16% of Qatari males, and none of the Qatari females. HCM was found in 0.15% of non-Qataris, 0.18% of the non-Qatari males, and 0.05% of the non-Qatari females [Table 2]. Patients were of different nationalities as shown in Table 3.

Table 2

Prevalence of HCM

Table 3

Prevalence of HCM according to nationality and gender

Baseline characteristics

Mean age (± SD) was 47 years (± 12.2), for males 47 (± 12) y, and for females 49 (± 19) y. There were 27 (77%) patients referred from the outpatient clinic and 11 (23%) were inpatients.

Echocardiographic measurements

EF was 0.61 (±5.3). The septum was affected alone in 17 (44.7%) cases, with other segments in 16 (42%) cases and was spared in 5 cases (13.2%). The maximum septal dimension was 3.1 cm. The mean septum and (±SD) was 1.9 (±0.6) cm. The maximum LV dimension was 5.6 cm and the mean was 4.5 (±0.70) cm [Table 4].

Table 4

Echocardiographic measurements of patients with HCM

Patterns of LV hypertrophy

Patients were divided into groups according to the pattern and degree of left ventricular hypertrophy pattern [Table 5]. Four patterns of hypertrophy were described; Pattern 1 (P1) with septal hypertrophy alone, Figure 1, pattern 2 (P2) with septal and other segments hypertrophy but sparing the apex, Figure 2, pattern 3 (P3) with apical segments together with any other segment hypertrophy, Figure 3, and pattern 4 (P4) with apical hypertrophy alone, Figure 4. The most common pattern was P 1; 17 cases (44.7%); P 2 was 6 cases (15.8%); P 3 was 10 cases (26.3%); and P 4 was 5 cases (13.2%) [Table 5].

Table 5

Prevalence of different patterns of hypertrophic cardiomyopathy

Figure 1

Pattern 1 of hypertrophy with septum hypertrophy alone (arrow) in short axis and apical long axis views

Figure 2

Pattern 2 hypertrophy of more than one segment (arrows) in short axis and long axis but sparing the apex

Figure 3

Pattern 3 with hypertrophy affecting more than one segment including the apex (arrows) in short axis and long axis views

Figure 4

Pattern 4 with no hypertrophy of the basal segments as shown in the short axis view and hypertrophy (arrows) affecting the apex only as shown in the apical 4 chamber view

Left ventricular obstruction

No obstruction was found in 19 (50%) patients. LV outflow obstruction was found in 13 (34.2%) cases, with a rest gradient ranging from 20 to 112 and a mean (+ SD) of 45.9 (+ 29.8) mmHg. Mid cavity obstruction was found in 6 (15.8%) cases, with a rest gradient ranging from 30 mmHg to 45 mmHg and a mean of 30.7 (±10.7) mmHg [Tables 6 and 7].

Table 6

Relation between patterns of LV hypertrophy and different levels of obstruction in patients with hypertrophic cardiomyopathy

Table 7

Symptoms in patients with hypertrophic cardiomyopathy with different levels of obstruction

Reasons for referral

Patients had different referral reasons. Twenty one (55.3%) patients were referred because of chest pain, 15 (39.5%) palpitations, 15 (39.5%) shortness of breath, and 5 (13.2%) syncope. Nine patients (23.7%) were asymptomatic and were referred because of murmur during routine examination. Abnormal ECG was found in 29 (76.3%) [Tables 7 and 8].

Table 8

Symptoms in patients with hypertrophic cardiomyopathy and in different patterns of LV hypertrophy

Family history

Family history of HCM was asked in only 27 patients (71%). Of those 10/27 (37%) had known family history of HCM and 17/27 (63%) gave no family history.

Investigations

Stress thallium was performed in 7 patients. All were negative for myocardial ischemia. Coronary angiography was performed in 12 and only 2 had evidence of coronary artery disease. Holter was performed in 18 and their results were: 9 showed abnormalities; one had sustained VT and he had an ICD inserted, one had non sustained VT, 5 had frequent PVC's and 2 had paroxysmal AF.

ECG data

Of the 38 patients; Romhilt-Estes score (RES) was > 5 in 29 (76.3%). R or S wave ≥ 20 mm in any limb lead or S wave in V1 or V2 ≥ 30 mm or R wave in V5 or V6 ≥ 30 mm(RS) was found in 24 (63.4%), secondary ST-T changes typical of LVH (SST) was found in 25 (65.8%), P terminal force in V1 ≥ 1 mm in depth or 40 msec duration (PV1) was found in 20 (52.6%), QRS axis ≥ -30° (Axis 30) in 15 (39.5%), QRS duration ≥ 90 msec (QRSd90) in 24 (63.2%) and intrinsicoid deflection in V5 or V6 ≥ 0.05 sec (IV56) in 6 (15.8%). ECG changes in different patterns of hypertrophy and prevalence of ECG evidence of left ventricular hypertrophy is shown in Tables 8 and 9.

Table 9

ECG assessment of LV hypertrophy in patients with hypertrophic cardiomyopathy and different patterns of hypertrophy

Pattern of LV hypertrophy and ECG changes

ECG evidence of LV hypertrophy was found in 29 (76.3%). Whereas, ECG abnormalities were found in all of P3 and P4 it was found in only 58.8% of P1 and 66.7% of P2 [Table 9].

DISCUSSION

Hypertrophic cardiomyopathy is a genetically determined disease whose prevalence varies in different regions and ethnic groups. It is a major cause of morbidity and sudden cardiac death especially in young adults.

There are no published data of the prevalence of HCM in Qatar. Therefore, we analyzed our data in HGH in Qatar. This study is a retrospective descriptive cross sectional study which analyzed the prevalence of HCM who were evaluated at HGH echocardiography unit during the period of January 2008 up to December 2010.

The prevalence of HCM was 0.13%. Prevalence varied from 0 to 0.18 % in different age and ethnic groups as shown in Table 2. HCM was prevalent in 0.15% of males and 0.03 of females (5 times more common in males). Epidemiological investigations with diverse study designs have shown estimates for prevalence of HCM in the adult general population at about 0.2% (1:500).[89] Nevertheless, a good proportion of individuals harboring a mutant gene for HCM are undetected clinically. Our study is not a community screening study and our population were those referred for echocardiography, and therefore we expect it underestimates the phenotypic prevalence in the community. Also, it underestimates the genetic harboring population. Other studies relying on hospital referrals, have found similar prevalence and HCM was found in no more than 1% of outpatients.[9]

The prevalence in females was significantly less than expected. Most previous clinical reports showed a male majority ranging from 55% to 78%,[238-13] however, in our study females were even significantly under represented (males were 92%). This may reflect failed diagnosis due to reduced patient awareness,[8-1014] fewer indication for medical screening programs,[1315-18] and clinician bias[15] or delayed clinical presentation, which may be secondary to genetic and endocrine factors directly affecting phenotypic expression.[513] Indeed, a protective effect of estrogens on development of secondary hypertrophy has been shown in animal models.[19]

A major contributing factor in our study is the nature of the study population which was predominantly male (66.8% of the total population and 76.3% of the non-Qatari), which represented an immigrant working community rather than only native Qataris with a normal gender distribution. Lastly, our population were younger (mean age 47 y) and it is to be noted that previous studies have shown that male predominance were noted from adolescence to mid-life.[13]

Presence of left ventricular obstruction

Different gradient cut-offs have been proposed for segregating individual patients into hemodynamic subgroups, but rigorous partitioning into such hemodynamic categories according to gradient can be difficult because of the unpredictable dynamic changes that may occur in individual patients.[122021] In our study we used 20 mmHg as a rest cut-off and /or a 50 mm Hg as a provocative induced gradient. Some of our patients were on medical treatment; hence, we have chosen relatively low gradient obstruction in an attempt to include some of those patients.

Nineteen (50%) had no evidence of obstruction, 13 (34.2%) had LV outflow obstruction, and 6 (15.8%) had mid cavity obstruction. Previous studies have shown a wide range of LV outflow obstruction prevalence from 23 – 77%.[1320-22] Patients with LVOT obstruction were older than both other groups. Most of those with LVOT obstruction had pattern 2 of hypertrophy (76.9%). Most of patients with mid cavity obstruction (83.8%) presented with chest pain and all had ECG evidence of LV hypertrophy.

There is no universal classification of the pattern of left ventricular hypertrophy. The most commonly used is the Maron classification.[2324] Seventeen patterns were described.[5] We adopted a more simple four-pattern model, which took into account the number of segments involved in short axis and long axis distribution. Our patterns were a spectrum, which started by the involvement of the septum alone, pattern 1, the involvement of other segments but sparing the apex, pattern 2, the involvement of other segments including the apex, pattern 3, and lastly involving only the apex, pattern 4. The four patterns of LV hypertrophy showed no difference in age. All patients with pattern 4 presented with chest pain and had ECG evidence of LV hypertrophy. Sixty percent of them had shortness and 60% had palpitations. Patterns 1 and 2 showed less frequent symptoms and pattern 2 was the least symptomatic. ECG evidence of LV hypertrophy was present in 100% of pattern 3 and 4 and was least sensitive in pattern 1 (58.8%). This proposed four-pattern model was unique in its apparent relation to clinical presentation and ECG changes compared to other previously reported classifications. This relation maybe extrapolated to prognostic implications. Further, another model incorporating our four-patterns with levels of obstruction may be more informative, but the small number of patients in our study did not allow us to study this hypothesis.

Study limitations

This study analyzed the prevalence among patients referred for echocardiography and not among the community. The results reflect the geographic diversity of the residents of Qatar, the majority of whom are expatriates. As well, the results show a young male predominance. Still, such a study is required to evaluate the magnitude of the problem in Qatar before attempting nationwide survey studies. Our study analyzed the patients evaluated during this period, rather than those who were first diagnosed. Also, we had limitations inherent to a retrospective study, such as non standardized measurements and incomplete studies. We tried to overcome these limitations by thorough review of the files of the patients and re-evaluating the measurements by offline analysis. Provocative tests were not standardized and was not attempted in all patients. Some patients were on medications, which might alter the measured pressure gradient during the study or might have even abolished such a gradient in some and thus underestimated the prevalence of the obstructive type.

CONCLUSIONS

The prevalence of HCM in HGH - Qatar is 0.13%. LVOT obstruction occurred in 34.2% and mid cavity obstruction in 15.8%. We proposed a new method of classifying the distribution of hypertrophy (four-pattern hypertrophy), which appeared to differ in their clinical presentation and ECG abnormalities. Our study also underlines the need for designing special protocols for registration and investigation of HCM.