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[From myocardial hypertrophy to heart failure: role of the interstitium]
A Barsotti1, F L Dini, V Nardini
1Istituto di Clinica Cardiovascolare, Università degli Studi G D'Annunzio, Chieti.
Insights
Abnormalities in the heart's interstitial space, including edema and fibrosis, are critical in the progression from myocardial hypertrophy to heart failure. These changes impact coronary perfusion and can lead to myocyte death and heart failure.
Area of Science:
- Cardiovascular Biology
- Cardiac Pathophysiology
- Extracellular Matrix Remodeling
Context:
- Myocardial hypertrophy progresses to heart failure through critical interstitial space abnormalities.
- Extracellular edema and altered coronary subendocardial perfusion are linked to interstitial fibrosis development.
- Cardiac studies show increased interstitial fluid volume and pressure during overload response.
Purpose:
- To elucidate the role of cardiac interstitial abnormalities in the transition from hypertrophy to heart failure.
- To explore the mechanisms linking interstitial edema, fibrosis, and impaired coronary perfusion.
- To understand the contribution of hormonal control and microcirculatory changes to heart failure progression.
Summary:
- Interstitial space changes, including edema and fibrosis, are key in heart failure development following myocardial hypertrophy.
- Activation of the renin-angiotensin-aldosterone system drives collagen accumulation, leading to fibrosis.
- Impaired lymphatic drainage and increased endothelial permeability contribute to acute heart failure.
- Subendocardial fibrosis restricts coronary flow, causing ischemia and myocyte necrosis.
- A positive feedback loop of perfusion impairment, edema, and remodeling perpetuates heart failure.
Impact:
- Provides insights into the structural and pathophysiological mechanisms driving heart failure progression.
- Highlights the interstitial space as a therapeutic target for hypertrophic heart disease.
- Enhances understanding of the interplay between mechanical stress, fluid dynamics, and fibrosis in the failing heart.
Abstract:
In the progression from myocardial hypertrophy to heart failure, abnormalities in the interstitial space of the heart seem to play a critical role. The formation of an extracellular oedema and the alterations in coronary subendocardial perfusion are associated with the development of interstitial fibrosis. Cardiac experimental studies documented the presence of augmented interstitial fluid volume and pressure and a subsequent remodelling of the fibrillar network of the extracellular space of the myocardium during the phases of the cardiovascular response to a sudden overload. Variations of the Starling's forces balance caused by enhanced endothelial permeability or due to an impairment of cardiac lymphatic drainage may contribute to the development of an acute heart failure. During stable hyperfunction, the organization of a chronic oedema should account for interstitial changes in the hypertrophic myocardium. Reactive fibrosis seems to be under hormonal control. The activation of the renin-angiotensin-aldosterone system is responsible for interfascicular and intercellular accumulation of fibrillar collagen within the cardiac interstitium. Perivascular fibrosis in the subendocardium may impair intramyocardial distribution of coronary flow. When an inadequate hypertrophy occurs, because of an elevation in ventricular wall stress, myocardial oxygen consumption rises and this may lead to the exhaustion of coronary blood flow reserve in the subendocardial layers. This underperfusion may be responsible for the development of myocardial ischemia. Coronary hemodynamic changes in the microcirculation as those prompted by interstitial alterations may contribute to the onset of myocyte necrosis and to the formation of restorative fibrosis. The progressive mechanical overload of the spared hypertrophied myocytes could explain the initiation of a positive feedback mechanism which perpetuates endomyocardial perfusion impairment, interstitial oedema and remodelling, finally, causing myocyte deaths and fibrous tissue proliferation. These structural alterations and their pathophysiological counterparts appear to be closely related to the evolution from compensatory hypertrophy to chronic myocardial failure in hypertrophic heart disease.