Role of the renin-angiotensin-aldosterone system and inflammatory processes in the development and progression of diastolic dysfunction.
ABSTRACT Left ventricular diastolic dysfunction represents a frequent clinical condition and is associated with increased cardiovascular morbidity and mortality. Diastolic dysfunction is the most common cause of HF-PSF (heart failure with preserved ejection fraction). Therefore it becomes important to understand the pathophysiological mechanisms underlying diastolic dysfunction, as well as the effective therapeutic strategies able to antagonize its development and progression. Among the complex pathophysiological factors that may contribute to the development of diastolic dysfunction, the RAAS (renin-angiotensin-aldosterone system) has been shown to play a significant role. Paracrine and autocrine signals of the RAAS promote structural and functional changes in the heart largely linked to increased myocardial fibrosis. Enhanced and dysregulated activity of the RAAS also contributes to the development of volume overload and vasoconstriction with subsequent increases in left ventricular diastolic filling pressures and a higher susceptibility of developing CHF (congestive heart failure). More recently, it has also been suggested that the RAAS may play a role in triggering myocardial and vascular inflammation through the activation of different cell types and the secretion of cytokines and chemokines. RAAS-induced myocardial inflammation leads to perivascular myocardial fibrosis and to the development or progression of diastolic dysfunction. For these reasons pharmacological blockade of the RAAS has been proposed as a rational approach for the treatment of diastolic dysfunction. In fact, ACEIs (angiotensin-converting enzyme inhibitors), ARBs (angiotensin II receptor blockers) and AAs (aldosterone antagonists) have been demonstrated to delay the development and progression from pre-clinical diastolic dysfunction towards CHF, as well as to reduce the morbidity and mortality associated with this condition.
Article: Diagnosis and management of left ventricular diastolic dysfunction in the hypertensive patient.[show abstract] [hide abstract]
ABSTRACT: The progression of hypertensive involvement toward heart failure includes myocardial fibrosis and changes of left ventricular (LV) geometry. In the presence of these abnormalities, diastolic abnormalities occur and are defined as LV diastolic dysfunction (DD). They include alterations of both relaxation and filling, precede alterations of chamber systolic function and can induce symptoms of heart failure even when ejection fraction is normal. The prevalence of heart failure with normal ejection fraction (HFNEF) increased over time whereas the rate of death from this disorder remained unchanged. In this view, diagnosis, prognosis, and therapeutic management of DD and HFNEF in hypertensive patients is a growing public health problem. DD may be asymptomatic and identified occasionally during a Doppler-echocardiographic examination. This tool has gained, therefore, important clinical position for diagnosis of DD. Comprehensive assessment of diastolic function should be done not by a simple classification of DD progression but by estimating the degree of LV filling pressure (FP), a true determinant of symptoms and prognosis. This can be obtained by different ultrasound maneuvers/tools but the ratio between transmitral E velocity and pulsed tissue Doppler-derived early diastolic velocity (E/e' ratio) is the most feasible and accurate. The identification of left atrial enlargement may be useful in uncertain cases. The recommended management of DD in hypertensive patients should correspond to blood pressure (BP) lowering and to the attempt of reducing LV mass and normalizing LV geometry. Prospective studies with well-defined entry criteria are needed to establish whether this approach could reflect a better prognosis.American Journal of Hypertension 12/2010; 24(5):507-17. · 3.18 Impact Factor