Abstract
The interventricular septum is recognized as the first region to undergo remodeling, and a septal bulge is described as an early echocardiographic sign of hypertensive heart disease. Using third-generation microscopic ultrasonography in an animal model, we validated, for the first time, that remodeling originates in the basal septum, presenting as basal septal hypertrophy (BSH), an early imaging biomarker, and subsequently progresses to other regions, leading to tissue dysfunction and heart failure. We have termed this finding the "stress septal sign" (Triple S) because a variety of stress stimuli, such as treadmill exercise or pressure overload from aortic banding in animals, induced BSH, a region with more intensive sympathetic innervation than the mid-apex. This finding also represents a conjunctive point between functional etiologies, such as hypertension, and emotional etiologies that precipitate acute stress cardiomyopathy. Microscopic analysis of the remodeling revealed that hemodynamic stress has a specific effect on cardiac geometry. The Triple S is associated with exercise-induced hypertension and high stress scores in patients with hypertension. Furthermore, three-dimensional segmental remodeling is more effective than cross-sectional measurements for detecting the impact of superimposed multiple stressors. A high-rate pressure product and blood pressure variability in patients exhibiting the Triple S should be managed comprehensively through an integrated approach to stress and hypertension to avoid high mortality in clinical practice. A precise etiologic evaluation of incidentally detected BSH may contribute to the early diagnosis of hypertensive disease. The integrated and timely management of stress and hypertension is important for patients presenting with the Triple S and high stress scores. This management strategy may provide a practical solution for avoiding the adverse hypertensive consequences of global remodeling and maladaptation to superimposed multiple stressors.