[Heart failure with preserved ejection fraction: a systemic disorder?]

When the syndrome of heart failure (HF) is due to left ventricular (LV) systolic dysfunction the clinical manifestations and natural history of the syndrome depend primarily on the severity of LV systolic dysfunction. In contrast, when the syndrome is attributed to LV diastolic dysfunction multiple comorbidities are responsible for the clinical manifestations and the natural history of the syndrome. The present review underscores the multifactorial pathogenesis of the syndrome of HF associated with LV diastolic dysfunction that nowadays is more properly referred to as HF with preserved LV ejection fraction (HFpEF) than to diastolic HF. The prognosis is similarly poor whether HF is due to systolic dysfunction or associated with diastolic dysfunction. The cause of death that is commonly non-cardiovascular in HFpEF supports the pathogenic importance of comorbidities in this condition. Hypertension, chronic kidney disease (CKD), diabetes, obesity and sleep disorder breathing are among the most frequent comorbidities in HFpEF. These comorbidities account for the multiple clinical presentations of the syndrome of HFpEF. Limited functional capacity is in HFpEF largely related to the downward spiral between CKD mediated fluid accumulation and LV stiffness as well as altered ventricular-vascular coupling. The diagnosis of HFpEF currently relies on 2D-Doppler echocardiography findings of impaired LV relaxation and increased LV stiffness and to a lesser extent on biomarkers. Owing to both lack of stringent inclusion and exclusion enrollment criteria and mistaken therapeutic target, placebo-controlled randomized therapeutic trials have been so far negative in HFpEF.