Topic Reviews A-Z
Chronic Heart Failure - Heart Failure with Preserved Ejection Fraction Topic Review
Introduction
Chronic heart failure occurs when either the left ventricle, the right ventricle, or both require elevated filling pressures to maintain cardiac output. Heart failure is a syndrome, not a specific disease, and occurs as a final common pathway in multiple disease states.
Heart failure (HF) can be due to the following:
- Systolic dysfunction with reduced ejection fraction - HFrEF
- Diastolic dysfunction abnormal relaxation or impaired filling with preserved ejection fraction - HFpEF
- Valvular heart disease
- Pulmonary hypertension with right HF
- Arrhythmia
- High output HF (ie, severe anemia, arteriovenous malformations)
The section presents a review of diastolic congestive heart failure, commonly called HFpEF. Reviews of systolic congestive HF, or HFrEF, valvular heart disease, pulmonary hypertension and right HF, and high output HF are discussed elsewhere.
Pathophysiology –HFpEF
Left ventricular diastolic dysfunction is manifest when increased filling pressure (ie, left atrial, pulmonary capillary wedge and pulmonary artery diastolic pressures) is required in order to maintain cardiac output. HFpEF connotes diastolic dysfunction despite a normal ejection fraction. Diastolic dysfunction also occurs frequently in patients with HFrEF. [Hurst’s The Heart Section 11:13a,14a-b,15a]
Although the renin-angiotensin-aldosterone system is activated in HFpEF, it is not as prominent as with systolic HF, and cardiac remodelling is less marked.
The figure below shows a schematic of the negative neurohormonal feedback mechanisms that become active in worsening HF:
Etiology –HFpEF
Some of the underlying causes of HFpEF are listed below:
- Hypertensive heart disease
- Restrictive and infiltrative cardiomyopathies such as amyloid, sarcoidosis and/or hypothyroidism
- Cancer chemotherapy
- Sustained tachyarrhythmias
- “Presbycardia”
Hypertension may cause left ventricular hypertrophy (LVH) and impaired relaxation. Over time, this condition progresses, resulting in higher degrees of diastolic dysfunction, low cardiac output and symptoms of congestive HF.
Restrictive cardiomyopathies frequently involve myocardial infiltration — amyloid deposition, for instance. This results in diastolic relaxation abnormalities and, eventually, the syndrome of HFpEF.
Obstruction to LV outflow leads to left ventricular hypertrophy and diastolic dysfunction. Sustained tachycardia, such as unrecognized and uncontrolled atrial fibrillation with a rapid ventricular response, may occasionally result in HFpEF symptoms. However, more commonly, tachycardia-induced cardiomyopathy results in reduced ejection fraction.
The aging process of the heart is not well understood, but fibrotic changes in the myocardium typically occur with advanced age. This results in relaxation abnormalities that are often present by the age of 60. This can progress in the elderly, causing significant diastolic impairment and HFpEF.
Symptoms –HFpEF
The symptoms of HF include fatigue, exercise intolerance, dyspnea and eventually edema. The symptoms are similar regardless of the etiology of the heart disease, and reflect either impaired cardiac output or fluid retention. Symptoms are important in differentiating left ventricular failure from right ventricular failure.
Early in the course of left ventricular failure, the compensated right heart generates elevated pulmonary artery and wedge pressures that may result in dyspnea, pulmonary congestion or pulmonary edema.
As HF progresses, chronic elevation of pulmonary pressures lead to the development of right ventricular failure. The negative feedback mechanisms outline above result in fluid retention and systemic venous congestion.
Right HF symptoms include lower extremity-dependent edema. When the legs are elevated at night, reabsorption of extracellular fluid increases right heart preload, the fluid redistributes centrally and may cause pulmonary congestion with orthopnea (dyspnea while laying flat) or paroxysmal nocturnal dyspnea (PND). Systemic venous congestion may also lead to hepatic congestion with right upper quadrant abdominal pain.
Symptoms related to low cardiac output include fatigue, exercise intolerance and weakness. In extreme cases, cardiac cachexia can occur.
Clinical Classification –HFpEF
Two HF classification systems are widely used: the New York Heart Association (NYHA) functional classification and the American College of Cardiology and American Heart Association (ACC/AHA) staging system. [Heidenreich 2022;10a(e905)]
The NYHA system categorizes patients into one of four classes based on a health care professional’s subjective assessment of the patient’s symptoms:
Class I: No symptoms of HF
Class II: Symptoms of HF with moderate exertion, such as walking two blocks or climbing two flights of stairs
Class III: Symptoms of HF with minimal exertion such as walking one block or one flight of stairs, but no symptoms at rest
Class IV: Symptoms of HF at rest
The ACC/AHA staging categorizes patients into one of four stages on the basis of risk factors, cardiac structural abnormalities associated with HF and the presence of symptoms of HF: [Heidenreich 2022:10a]
Stage A: At high risk for HF but without symptoms, structural heart disease or cardiac biomarkers of stretch or injury
Stage B: Pre-HF, defined as no signs or symptoms of HF but evidence of one of the following: structural heart disease, evidence of increased filling pressures or risk factors plus increased levels of BNPs or persistently elevated cardiac troponin
Stage C: Structural heart disease with prior or current symptoms of HF
Stage D: Marked HF symptoms that interfere with daily life and with recurrent hospitalizations despite attempts to optimize guideline-directed medical therapy (GDMT)
In addition to focusing on different classificatory parameters, the NYHA functional classification differs from the ACC/AHA heart failure staging in that NYHA allows movement from any one class to another while the ACC/AHA system only allows unidirectional progression of stages (A→B→C→D). [Heidenreich 2022:10a]
Diagnosis –HFpEF
In general, diagnosis of HF is initially based on clinical findings on history and physical examination. However, in recent years, 2D and Doppler echocardiography has become the standard laboratory method to confirm the clinical diagnosis and assess cardiac structure and function. [Metra 2017:3d]
There are four grades of echocardiographic diastolic dysfunction, as described below. Clinical manifestations of congestive HF may occur once grade II diastolic dysfunction is present, but not in the presence of grade I diastolic dysfunction (impaired relaxation).
Grade I (impaired relaxation): The E-wave velocity is reduced, resulting in E/A reversal (ratio < 1). The left atrial pressures are normal. The deceleration time of the E wave is prolonged, measuring greater than 200 milliseconds. The e/e’ ratio measured by tissue Doppler is normal.
Grade II (pseudonormal): This is pathological finding characterized by elevated left atrial pressures. The E/A ratio is normal (0.8-1.5), and the deceleration time is normal (160-200 ms), but the e/e’ ratio is elevated. The E/A ratio will be less than 1 with Valsalva. A major clue to the presence of grade II diastolic dysfunction vs. normal diastolic function is the presence of structural heart disease such as left atrial enlargement, left ventricular hypertrophy or systolic dysfunction. If significant structural heart disease is present, and the E/A ratio as well as the deceleration time appear normal, suspect a pseudonormal pattern. Valsalva distinguishes pseudonormal from normal as well as the e/e’ ratio. Diuresis can frequently reduce the left atrial pressure, relieving symptoms of HF and returning the hemodynamics to those of grade I diastolic dysfunction.
Grade III (reversible restrictive): This pathological finding is characterized by significantly elevated left atrial pressures. Also known as a “restrictive filling pattern,” the E/A ratio is greater than 2, the deceleration time is less than 160 ms and the e/e’ ratio is elevated. The E/A ratio changes to less than 1 with Valsalva. Diuresis can frequently reduce the left atrial pressure, relieving symptoms of HF and returning the hemodynamics to those of grade I diastolic dysfunction.
Grade IV (fixed restrictive): This finding is characterized by severely elevated left atrial pressures and indicates a poor prognosis. The E/A ratio is greater than 2, the deceleration time is low and the e/e’ ratio is elevated. The major difference distinguishing grade III from grade IV diastolic dysfunction is the lack of E/A reversal with the Valsalva maneuver (no effect will be seen with Valsalva). Diuresis will not have a major effect on the left atrial pressures, and clinical HF is likely established. Grade IV diastolic dysfunction is present only in very advanced HF and frequently seen in end-stage restrictive cardiomyopathies such as amyloid cardiomyopathy.
Treatment –HFpEF
Until recently, prospective randomized controlled interventional trials in HFpEF populations did not a firm evidence base for therapy, and therapy was thus aimed at symptom relief and management of comorbidities. However, recent trials showed effectiveness of several agents in the HFpEF population, and based on those, the 2022 ACC/AHA/Heart Failure Society of America guideline for the management of HF makes several recommendations: [Heidenreich 2022:55b]
- SGLT2 inhibitors can be beneficial in reducing CV death and HF hospitalizations in patients with HFpEF (Class IIa, level of evidence B).
- In selected patients with HFpEF, mineralocorticoid receptor antagonists may be considered to decrease hospitalizations, particularly for patients on the lower end of the EF range of HFpEF (Class IIb, level of evidence B).
- In selected patients with HFpEF, angiotensin receptor/neprilysin inhibitors may be considered to decrease hospitalizations, particularly for patients on the lower end of the EF range of HFpEF (Class IIb, level of evidence B); the guideline notes that the most benefit was observed in women and in patients with EF of 57% or lower.
- In selected patients with HFpEF, angiotensin receptor blockers may be considered to decrease hospitalizations, particularly for patients on the lower end of the EF range of HFpEF (Class IIb, level of evidence B).
The guideline states that routine use of nitrates or phosphodiesterase-5 inhibitors to increase activity or quality of life is ineffective.
The guideline also states that patients with HFpEF and hypertension should have antihypertensive medications titrated to attain guideline-recommended blood pressure targets (Class I, level of evidence C) and that management of atrial fibrillation can be useful to improve symptoms in patients with HFpEF (Class IIa, level of evidence C).
As in patients with HFrEF, in patients with HFpEF, diuretics are recommended to reduce congestion and improve symptoms (Class I, level of evidence B). [Heidenreich 2022:56a]