Echo-Based Approach to the Management of Heart Failure With Preserved Ejection Fraction

Introduction

Heart failure is a clinical syndrome resulting from structural and functional impairment of ventricular filling or ejection of blood. Patients with HF can be divided into those with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), and recent literature has also defined an intermediate category of midrange ejection fraction (HFmrEF). Diastolic dysfunction is a central derangement found within all HF patients, regardless of EF. Furthermore, although EF may be preserved, subtle systolic dysfunction is often present in HFpEF as evidenced by deformation imaging. In addition to impairment in LV diastolic properties, those with HFpEF may suffer from a multitude of associated conditions, including right heart dysfunction, pulmonary hypertension (PH), ventricular-arterial uncoupling, left atrial (LA) dysfunction, chronotropic incompetence, atrial tachyarrhythmias, and maladaptive peripheral vascular and skeletal abnormalities. Complementary to the diastolic LV assessment, evaluation of several of these associated conditions makes echocardiography an essential tool in the management of HFpEF.

Heart failure is not a specific disease entity, instead it is a clinical syndrome that develops as a result of several potentially different forms of underlying cardiovascular (CV) disease. Risk factor acquisition and the subsequent response to risk mitigation strategies, combined with intrinsic individual factors, determine whether structural cardiac abnormalities will develop. Antecedent structural changes lead to the eventual development of symptoms and thus the clinical HF syndrome. With this in mind, the American College of Cardiology/American Heart Association (ACC/AHA) have developed a HF staging system ( Table 35.1 ). Interventions are aimed at modifying risk factors (stage A), treating structural heart changes (stage B), and reducing morbidity and mortality (stages C and D). Although this conceptual framework has been largely adopted in the HFrEF realm, uptake of this concept into the management and study of HFpEF has been lacking despite widespread agreement that comorbid disease management is imperative in HFpEF treatment.

Contrary to common perception, mean survival for patients suffering from HFpEF is similar to those with HFrEF. Mode of death in both HFpEF and HFrEF is most commonly related to CV causes, although non-CV causes of death likely represent a more sizable contributor in HFpEF than in HFrEF. Comorbid disease states likely contribute to both the development and progression of diastolic dysfunction, as well as predict recurrent hospitalizations and clinical deterioration. Several echo-derived variables have been associated with increased risk of morbidity and mortality in HFpEF ( Box 35.1 ). Worsening of diastolic function on serial echocardiographic studies over time is an independent predictor of increased mortality.

Optimal management strategies for HFpEF remain to be defined. Several large-scale phase III therapeutic clinical trials in HFpEF have been conducted, and all failed to meet their primary end point. Lack of clear, beneficial evidence-based therapy of HFpEF represents one of the largest unmet needs in CV disease management. Several potential explanations for these neutral results exist, including inconsistent inclusion criteria with respect to the presence and severity of diastolic dysfunction by echocardiography, differing EF and circulating natriuretic peptide cutoff values, high representation of confounding comorbid conditions, and an overall heterogeneity of structural abnormalities within study populations. The latter recognition of heterogeneity within HFpEF pathogenesis and characterization has led to the concept of phenotyping of distinct HFpEF subtypes.

Although convincing clinical outcomes data are lacking, echocardiographic-derived diastolic function following specific treatment strategies may inform the provider of structural and functional response to therapy. The echocardiographic-based approach to management of HFpEF can broadly be divided into the study of highly load-dependent variables related to real-time volume and pressure status versus relatively load-independent variables related to chronic structural remodeling. Furthermore, LA function, PH, right heart function, and ventricular-arterial coupling can readily be assessed with echocardiography; all are of great importance in HFpEF management.

Pathophysiology

The field’s understanding of HFpEF pathophysiology has exploded in recent years. Once viewed purely as a LV disease of impaired relaxation and increased elastic stiffness, we now know that a multitude of factors influence this condition. Broadly, the pathophysiology of HFpEF can be divided into central and peripheral mechanisms, several of which are readily assessed with echocardiography. Central mechanisms include impaired LV relaxation and progressive stiffness, subclinical LV systolic dysfunction, LA dysfunction, PH, right heart failure, atrial tachyarrhythmias, chronotropic incompetence, atrial dysfunction, coronary microvascular rarefaction, and endothelial dysfunction. Peripheral mechanisms include systemic hypertension, arterial endothelial dysfunction, renal insufficiency, and poor peripheral oxygen extraction by skeletal muscle. Emerging data support systemic inflammation as a principal driver of multiorgan dysfunction that leads to cardiac remodeling and arterial stiffening.

LA Dysfunction

Abnormal diastolic suction function in HFpEF leads to impaired transmitral diastolic flow patterns apparent in traditional indices such as transmitral Doppler profile, as well as more sophisticated methods, including particle imaging velocimetry and vortex formation analysis. Progressive LV diastolic dysfunction leads to impaired LA emptying resulting in LA dysfunction. Chronic LA dysfunction manifests with LA enlargement, thus LA size may be viewed as a potential biomarker of the severity and chronicity of diastolic dysfunction. LA function has been divided into three phases: reservoir, conduit, and active contraction. During reservoir phase the left atrium stores pulmonary venous return during LV contraction and isovolumetric relaxation. With mitral valve opening, the left atrium acts as a conduit transferring blood passively into the left ventricle. Finally, the left atrium actively contracts contributing to late LV filling. Three-dimensional (3-D) echocardiography allows quantification of LV filling volume resulting from each atrial phase, and deformation imaging allows further physiologic assessment of LA function ( Fig. 35.5 ). The degree of decrement in peak LA strain measured during reservoir function has been associated with increasing degrees of diastolic dysfunction. Depressed LA contractile function is associated with increased LV filling pressures, and LA contraction contributes progressively less to LV filling volume with worsening grades of diastolic dysfunction. Impaired LA strain response to exercise is associated with right ventricular (RV)–pulmonary artery (PA) uncoupling and exercise ventilation inefficiency. Chronic LA hypertension and dysfunction lead to elevated pulmonary capillary wedge pressure (PCWP) and PH.