Heart Failure in Patients with Preserved Ejection Fraction: Questions Concerning Clinical Progression

Abstract

Over the last two decades, important advances have been made in explaining some pathophysiological aspects of heart failure with preserved ejection fraction (HFpEF) with repercussions for the successful clinical management of the syndrome. Despite these gains, our knowledge for the natural history of clinical progression from the pre-clinical diastolic dysfunction (PDD) until the final clinical stages is significantly limited. The subclinical progression of PDD to the clinical phenotype of HFpEF and the further clinical progression to some more complex clinical models with multi-organ involvement, similar to heart failure with reduced ejection fraction (HFrEF), continue to be poorly understood. Prospective studies are needed to elucidate the natural history of clinical progression in patients with HFpEF and to identify the exact left ventricular remodeling mechanism that underlies this progression.

Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases

“…The clinical phenotype of patients with reduced ejection fraction (HFrEF) is extensively studied and understood but the clinical phenotype and natural history of patients with preserved ejection fraction (HFpEF) remain poorly defined [49]. The subclinical progression of the pre-clinical diastolic dysfunction (PDD) to the classical clinical phenotype of HFpEF is incompletely understood [49].…”

“…The subclinical progression of the pre-clinical diastolic dysfunction (PDD) to the classical clinical phenotype of HFpEF is incompletely understood [49]. In HFrEF syndrome, systems biology approach explains better the importance of neurohormonal compensatory regulatory mechanisms like SAS, NPS and RAAS.…”

“…The clinical understanding of HFpEF syndrome is increasing when examined with systems biology methodology, instead of the classical Oslerian method. Extensive prospective studies are required to comprehend the natural history of clinical progression in HFpEF patients and to determine the associated neurohormonal and left ventricular remodeling mechanisms that are involved [49]. …”

Altered Heart Rate Turbulence and Variability Parameters Predict 1-Year Mortality in Heart Failure with Preserved Ejection Fraction

“…Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical syndrome affecting around 50% of all HF patients [ 1 ] and increasing in prevalence by about 1% annually, predominantly owing to the changing age, demographics and increasing prevalence of obesity in western societies [ 2 ]. It is characterised by significant morbidity and extremely grim prognosis, with a 5-year mortality rate reaching over 75% in most affected individuals [ 3 , 4 , 5 ].…”

“…With emerging new and revolutionary treatment strategies for the HFpEF patient population, prognostication of disease progression and patient deterioration is becoming increasingly important in order to build reliable prognostic models that would allow medical professionals and patients to develop realistic expectations about disease prognosis and choose the most appropriate monitoring and therapeutic strategies [ 3 , 4 ]. In recent years, evidence has accumulated that, aside from well-established HF-related clinical predictors, such as New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), systolic blood pressure, QRS complex duration, atrial fibrillation (AF), or N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) [ 2 ], specific subclinical parameters, closely related to distinctive pathophysiological derangements observed in HFpEF, can provide crucial insight into the disease progression and, therefore, can be pivotal in tackling the HFpEF burden [ 1 , 6 , 7 ].…”