Discussion
Compared with hypertensive patients without ApHCM, those with hypertension and ApHCM had 1) more left ventricular systolic and diastolic dysfunctions; 2) decreased apical longitudinal and radial strains without a base-to-apex gradient; 3) constantly reduced apical anterior and lateral wall strains irrespective of strain measurement method; 4) independently reduced global longitudinal deformation. Interestingly, these results were obtained from patients with normal left ventricular ejection fractions, highlighting the evidence that alterations of myocardial strain are early contractile abnormalities in hypertensive patients with ApHCM.
The outcomes of patients with ApHCM are not as benign as previously thought. Moon et al. found that the presence of hypertension was the most negative determinant of poor clinical outcomes in patients with ApHCM. Consistent with this report, we also found that ApHCM conferred a negative impact on hypertensive patients in terms of systolic and diastolic functions. A reduced Sm, which indicates impaired myocardial contractility, could represent consequent subclinical systolic dysfunction despite a normal left ventricular ejection fraction. Furthermore, our patients had diastolic dysfunction as evidenced by a dilated left atrium, longer IVRT, and higher diastolic function grade as noted by others, which suggests that local apical hypertrophy could affect global left ventricular diastolic function. With impaired left ventricular systolic and diastolic functions of ApHCM, the left ventricular stroke volume is consequently reduced despite a normal left ventricular ejection fraction.
In hypertrophic cardiomyopathy patients, longitudinal strain is reduced heterogeneously as assessed by magnetic resonance imaging tagging. Similarly, Yang et al. also found that longitudinal strain is reduced in both septal hypertrophic cardiomyopathy and ApHCM. The subendocardial region contributes primarily to the longitudinal mechanics of the left ventricle. Therefore, the subendocardial layer is vulnerable to the effect of pressure and ischemia that are more commonly observed in hypertrophic cardiomyopathy. Abnormal myocardial capillary density and microvascular dysfunction occur in the hypertrophic myocardial segments of patients with ApHCM. These processes cause pronounced relative ischemia in the subendocardial layer, which may result in the formation of fibrotic tissue in the hypertrophic apex of hearts with ApHCM. Normally, left ventricular strains are heterogeneous: both the longitudinal and circumferential strains are higher in the apical and middle segments than basal segments. Continuous shortening in the longitudinal and circumferential direction would result in thickening in the radial direction for mass conservation. Therefore, the apical radial strain is lower, but the longitudinal and circumferential strains are higher than in the basal segment. We also found similar findings with further reduced apical radial strain in hypertensive patients with ApHCM than in hypertensive patients without ApHCM. These findings suggest that the hypertrophic apex of hearts with ApHCM is characterized by both morphological and functional abnormalities, which cause the disappearance of the base-to-apex gradient. In addition, we also observed attenuated longitudinal values in the middle ventricular segments relative to the basal segments, in contrast to the base-to-apex gradient in longitudinal values reported by Sun et al.. This finding appears to indicate that the pathologic ventricular hypertrophy extends beyond the apex into the middle and basal ventricular parts of hearts in cases of ApHCM.
With characteristic insonation angle independence, 2-dimensional speckle tracking echocardiography allows researchers to investigate cardiac mechanics not only globally, but also regionally; as a result, it is uniquely suited for the assessment of left ventricular apical deformation such as that of ApHCM. In the present study, hypertensive patients without ApHCM (control group) had lower than normal strain values, which is similar to the findings of Mizuguchi et al.. Based on the comorbidity of ApHCM in hypertensive patients, the left ventricular mechanics are worse than that in hypertensive patients without ApHCM. Inoue et al. found that left ventricular free walls, as well as hypertrophic septa, are dysfunctional in patients with hypertrophic cardiomyopathy, indicating the importance of the lateral wall function and structure. We also observed constantly reduced apical anterior and lateral wall strains irrespective of strain measurement method, suggesting that the left ventricular apical free walls are the most dysfunctional. The global 2-dimensional longitudinal strain is a surrogate parameter of myocardial fibrosis and cardiac events in patients with hypertrophic cardiomyopathy. Consistent with another study involving patients with decreased functional capacity, we noted that global longitudinal strain was independently associated with hypertension with ApHCM, suggesting that global longitudinal strain is a valuable marker in hypertensive patients with ApHCM. Subendocardial dysfunction is partly responsible for the association because the subendocardial region contributes primarily to the longitudinal strain, and the region is most vulnerable to the effects of pressure and ischemia in ApHCM.
With the electrocardiographic changes, some investigators found that the late and abrupt development of ApHCM occurs at an elderly age. The late development of ApHCM in the elderly may indicate a gene-environment interaction required for phenotypic manifestations. The "inducers" making the morphology of ApHCM in the adult patients are not known. Hypertension is associated with ApHCM, and its prevalences in the previous study cohort were 51%–67% which is higher than that of the general population. Although it is difficult to prove causality, this raises the possible role of sustained hypertension as an inducer of ApHCM. Therefore, we used hypertension as a baseline comorbidity to study the mechanical effect of ApHCM on left ventricular systolic deformation. Based on the presence of early left ventricular mechanic abnormalities in prehypertension, further studies on whether the impact of ApHCM on the left ventricle is localized to or extended beyond the apex would provide more information to understand left ventricular mechanics. Consistent with the prior study on prehypertension and hypertension, our study showed impaired basal and middle longitudinal strains even in the well-controlled hypertensive patients. With the presence of apical hypertrophy, the global longitudinal and circumferential strains decreased further although the blood pressure control was adequate. These findings indicate that ApHCM might develop progressively and incidentally even in the presence of well-controlled hypertension. Only regular follow-up with electrocardiography and/or echocardiography could identify these patients earlier.
Limitations
First, the retrospective design limited data analyses in the present investigation. Second, the number of patients included in the present study was small. Further research with a larger number of patients and a prospective design are needed to confirm our findings. Third, this study was conducted at a single tertiary center study. Therefore, our study population might not represent all patients with hypertension and ApHCM. Nonetheless, there are few if any studies using 2-dimensional speckle-tracking echocardiography for evaluating left ventricular mechanics in hypertensive patients with ApHCM. Therefore, our results provide valuable new insights into understanding the effects of pathological apical hypertrophy on left ventricular function in patients with hypertension. Finally, the incomplete coverage of apical hypertrophy might limit the strain analysis in patients with ApHCM.