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Review
, 9 (5), 91-108
eCollection

Novel Paradigms in the Therapeutic Management of Heart Failure With Preserved Ejection Fraction: Clinical Perspectives

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Review

Novel Paradigms in the Therapeutic Management of Heart Failure With Preserved Ejection Fraction: Clinical Perspectives

Fayez El Shear. Am J Cardiovasc Dis.

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a pathological complexity that decreases cardiac output and elevates the ventricular filling pressure. HFpEF is usually misdiagnosed and maltreated. HFpEF is usually correlated with excessive morbidity and mortality. The prevalence of HFpEF is growing, and there is a deficiency of evidence-based therapy, creating challenges for the physician with no effective management guidelines. Moreover, HFpEF is not equivalent to diastolic heart failure as previously thought, as diastolic dysfunction is not the only underlying mechanism related to HFpEF and sometimes may be absent. Several other mechanisms may work in concert to produce HFpEF syndrome, either cardiac related (chronotropic incompetence, a longitudinal left ventricular (LV) systolic dysfunction despite a normal ejection fraction) or extracardiac related (pulmonary hypertension, abnormal ventricular-arterial coupling, abnormal exercise-induced vasodilation, extracardiac volume overload). These complex pathophysiologic mechanisms indicate that HFpEF is heterogeneous and that this syndrome might be related to a vascular or an endothelial dysfunction or might be considered a cardiac manifestation of one or more systemic illnesses. The heterogeneity of HFpEF necessitates excluding many differential diagnoses. In addition, the multiple comorbidities that are inherent to this condition need to be controlled in order to achieve effective management. Taken together, these key mechanisms might contribute to the multiple difficulties in the management of HFpEF patients; these mechanisms also explain why medications used in patients with other heart conditions may or may not be successful in these patients. Novel therapies and clinical trials including paradigm shifts in therapeutic management are needed to effectively manage HFpEF. The current review article sheds light on novel paradigms related to pathologies, diagnoses, and strategies, along with some proposed recommendations and clinical options for effective management of HFpEF.

Keywords: HFpEF; Heart failure; clinical; management; new paradigm.

Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Phenotypes of diastolic dysfunction. HFpEF is a systemic syndrome with multiple phenotypes and contributing to diverse clinical representation, along with the degree of diastolic dysfunction and not necessarily the presence of right heart disease and pulmonary hypertension. Phenotype A is very common and is linked with few symptoms at rest including exercise induced left ventricle filling impairment and initial diastolic dysfunction. Phenotype B shows evident symptoms of heart failure, whereas phenotype C is related to overnight heart failure with severe pH. *HF: Heart Failure; LV: Left Ventricle; HFpEF: Heart Failure with preserved Ejection Fraction.
Figure 2
Figure 2
Proposed mechanisms of diastolic dysfunction. The mechanism of diastolic dysfunction is characterised by increased stiffness of left ventricle contributing to low cardiac output, thereby elevating diastolic pressure due to slow relaxation in early diastole and greater resistance in late diastole. Abnormal relaxation and increased stiffness in turn causes epicardial and microvascular ischemia, myocyte hypertrophy, diffuse fibrosis, fibro elastosis, pericardial constriction, capillary compression and venous engorgement. This causes volume overload of the contralateral ventricle and increased pulmonary pressure due to decreased stroke volume. *LV: Left Ventricle; SV: Stroke Volume; LVEDP: Left Ventricular End-Diastolic Pressure; COP: Center of Pressure.
Figure 3
Figure 3
Proposed causes of HFpEF. The figure shows the schematic representation of the cardiac and non-cardiac causes of HFpEF. Cardiac causes basically represent the cellular and biological changes within the heart in the following years of the disease; lead to the left ventricular hypertrophy and left atrial enlargement leading to atrial fibrillation and mitral regurgitation. *CRF: Chronic Renal Failure; DM: Diabetes Mellitus; COPD: Chronic Obstructive Pulmonary Disease; IDA: Iron Deficiency Anemia; LVH: Left Ventricular Hypertrophy; LAE: Left Atrial Enlargement; AF: Atrial Fibrillation; MR: Mitral Regurgitation.
Figure 4
Figure 4
Proposed strategies in the management of HFpEF. The schematic representation of treatment options for HFpEF depicts that treatment for acute HFpEF is same as that of HFrEF. On the other hand, for chronic treatment options can be either pharmacologic or non-pharmacologic or may be both. In pharmacologic, treatment of precipitating factors to decrease the complications of the condition and diuretics are given to reduce the congestive symptoms associated with hypervolemia, whereas physical activity and frequent visits to HFC are recommended in non-pharmacologic management of HFpEF. *HFrEF: Heart Failure with Low Ejection Fraction; AF: Atrial Fibrillation; HTN: Hypertension; HFC: Heart Failure Consultant.
Figure 5
Figure 5
Proposed therapies in HFpEF. The schematic representation depicts the current and future approach towards the therapeutic options of HFpEF. Future approaches can be either pharmacologic or non-pharmacologic. Pharmacologically promising drugs are Statin (lower cholesterol levels), PDEI5 (Inhibitor of Cyclic GMP in blood vessel lining) and NTG (blood vessels relaxation), however, the treatment options for HFpEF are now shifting towards new paradigm in which drugs are mainly anti-anginal. But, in future the focus will be mainly on treatment of comorbidities and precipitating factors. On the other hand, non-pharmacologic options include healthy diet, treatment of comorbidities and skilled persons for early diagnosis. *HFrEF: Heart Failure with Reduced Ejection Fraction; ACE1: Angiotensin Converting Enzymes 1; ARB: Angiotensin II Receptor Blockers; BB: Beta Blockers; HTN: Hypertension; AF: Atrial Fibrillation; MMP-1: Matrix Metalloproteinase-1; EPO alfa: Epoetin alfa.

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