Hypertensive Heart Disease: A Narrative Review Series—Part 1: Pathophysiology and Microstructural Changes

Abstract

Sustained hypertension causes structural, functional, and neurohumoral abnormalities in the heart, a disease commonly termed hypertensive heart disease (HHD). Modern concepts of HHD, including processes of remodeling leading to the development of various LVH patterns, HF patterns accompanied by micro- and macrovasculopathies, and heart rhythm and conduction disturbances, are missing in the available definitions, despite copious studies being devoted to the roles of myocardial and vascular fibrosis, and neurohumoral and sympathetic regulation, in HHD development and progression. No comprehensive and generally accepted universal definition and classification of HHD is available to date, implementing diagnostic criteria that incorporate all the possible changes and adaptions to the heart. The aim of this review series is to summarize the relevant literature and data, leading to a proposal of a definition and classification of HHD. This first article reviews the processes of initial myocardial remodeling, and myocardial and vascular fibrosis, occurring in HHD. We discuss important pathophysiological and microstructural changes, the different patterns of fibrosis, and the biomarkers and imaging used to detect fibrosis in HHD. Furthermore, we review the possible methods of targeting myocardial fibrosis in HHD, and highlight areas for further research.

Myocardial Interstitial Fibrosis in Hypertensive Heart Disease: From Mechanisms to Clinical Management

“…41 Therefore, it has been proposed that a variety of inflammatory (eg, monocyte chemoattractant protein-1) and noninflammatory (eg, cardiotrophin-1) cytokines, fibrogenic growth factors (eg, TGF-β [transforming growth factor-beta]), neurohumoral pathways (eg, the renin-angiotensin-aldosterone system and the adrenergic system), and epigenetic factors (eg, DNA methylation, histone modifications, and noncoding RNA) that are activated in HHD could contribute to the spread of MIF beyond the LV myocardium to other cardiac chambers. [42][43][44] The importance of these nonhemodynamic factors may also extend to the self-perpetuation of MIF in the absence of the initiating hypertensive stimulus (Figure 2). Indeed, it has been proposed that, in the case of reactive fibrosis, the fibrogenic process is not interrupted despite BP control, and that the deposition of fibrotic tissue progresses and becomes chronic, leading to deterioration of the architecture and properties of the myocardium and thus facilitating the development of clinical complications.…”

Challenges in Echocardiography for the Diagnosis and Prognosis of Non-Ischemic Hypertensive Heart Disease

“…Chronic AH triggers pathological processes, leading to structural and functional disturbances in the myocardium, like hypertrophy, fibrosis, and ischemia [6,17]. Chronic or sustained AH leads to pressure overload of the left cardiac cavities, induces change in gene expression, and confers simultaneous changes in the extracellular matrix and myocytes hypertrophy.…”

“…Replacement fibrosis, on the other hand, consists of scar tissue formed due to the loss of myocardial cells and their replacement by connective tissue following myocardial infarction or myocardial death from other causes [20]. It is still unclear whether those two types of myocardial fibrosis represent distinct processes, as they may occur simultaneously 6 . Hemodynamic factors, such as chronic pressure overload causing myocardial stress or injury, lead to increased collagen production (type I, type III) in the myocardium as a reparative mechanism.…”

“…Hemodynamic factors, such as chronic pressure overload causing myocardial stress or injury, lead to increased collagen production (type I, type III) in the myocardium as a reparative mechanism. Non-hemodynamic factors, such as the renin-angiotensin-aldosterone system, also play a significant role in myocardial fibrosis 6 .…”

“…From the pathophysiological perspective, unmanaged high BP induces high afterload and high LV filling pressures, leading to structural changes such as left ventricular hypertrophy (LVH) and fibrosis, and LA enlargement [6]. Besides this, HHD relates to systolic and diastolic LV dysfunction or a combination of them.…”