Management of Heart Failure With Preserved Ejection Fraction
Management of Heart Failure With Preserved Ejection Fraction
Objective: To provide an overview of heart failure with preserved ejection fraction (HFPEF), as well as its pathophysiology, diagnosis, and clinical evidence regarding its pharmacologic management.
Data Sources: Peer-reviewed articles were identified from MEDLINE, International Pharmaceutical Abstracts, and Current Contents (all 1966-August 2010) using the search terms heart failure with preserved ejection fraction, diastolic dysfunction, diastolic heart failure, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), digoxin, β-blockers, calcium-channel blockers, and vasodilators. Citations from available articles were also reviewed for additional references.
Study Selection and Data Extraction: Fourteen published manuscripts relating to pharmacologic management of HFPEF were identified.
Data Synthesis: The prevalence of HFPEF has continued to increase. Compared to heart failure with left ventricular systolic dysfunction, HFPEF has been largely understudied. Unlike in the management of heart failure with left ventricular systolic dysfunction, ACE inhibitors, ARBs, β-blockers, and aldosterone antagonists did not demonstrate mortality benefit in HFPEF, with the exception of one small study evaluating the use of propranolol. However, this study enrolled a small number of patients with recent history of myocardial infarction, which limited the generalizability of the results. Most of the current evidence centers on morbidity benefits and symptom reduction. One study showed that treatment with candesartan reduced hospital admissions in this population of patients. Management of HFPEF still focuses on optimally managing underlying diseases (eg, hypertension).
Conclusions: Much remains to be learned about the appropriate pharmacologic management of patients with HFPEF. Hypertension is in most cases the predominant contributor to its development and progression. For this reason, antihypertensive treatment, including ACE inhibitors, ARBs, β-blockers, and calcium-channel blockers, has been evaluated and is recommended to control the disease in this patient population, although these agents have not demonstrated significant benefit beyond blood pressure control. Further research into the pathophysiology of HFPEF may contribute to identifying the most optimal agent in managing this disease.
Heart failure is caused primarily by systolic or diastolic dysfunction. Systolic dysfunction is defined as an abnormality in systolic contraction leading to a low left ventricular ejection fraction (LVEF). Diastolic dysfunction is defined as an abnormality of diastolic distentability, filling, or relaxation of the left ventricle, regardless of whether the LVEF is preserved. However, since diastolic dysfunction is difficult to measure, the distinction between these patient groups is characterized in terms of their LVEF. Patients with heart failure are divided into those with reduced or preserved ejection fraction. Operationally, heart failure with preserved ejection fraction (HFPEF) has been defined, according to the Framingham criteria, as LVEF >45% and the absence of mitral stenosis, pericardial disease, or noncardiac causes of dyspnea, edema, and fatigue. However, clinical studies that evaluated pharmacologic management for HFPEF have used LVEFs of ≥35%, ≥40%, ≥45%, or ≥50% as the definition of HFPEF.
The prevalence of HFPEF has increased over time, from approximately 37% in the 1980s to over 50% in the 2000s, among all patients presenting with acute decompensated heart failure. HFPEF carries a significant morbidity and mortality burden (5-year mortality rate 65%). Impaired renal function, New York Heart Association (NYHA) functional class III or IV, male sex, and older age are important predictors of mortality. Compared to patients with left ventricular systolic dysfunction, patients with HFPEF have better survival rates (mortality rate 68% vs 65%). However, in the past 2 decades, the prognosis has improved for patients with systolic heart failure but not with HFPEF. Management of HFPEF has been largely understudied. The most updated guidelines developed by the American Heart Association and American College of Cardiology (AHA/ACC) stated that in patients with HFPEF, physicians should be vigilant in controlling blood pressure, providing optimal coronary artery disease treatment, and controlling ventricular rate. Diuretics are recommended for controlling pulmonary congestion and peripheral edema. Unlike in systolic ventricular dysfunction, besides managing underlying risk factors, there are no specific pharmacotherapeutic recommendations for management of the disease itself, especially regarding improvement in mortality.
On the other hand, the most recent Heart Failure Society of America (HFSA) guidelines recommend that angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors may be considered in HFPEF in the absence of other specific indications. The strength of evidence for this recommendation, however, is only C, indicating that it is based on expert opinions. The guidelines also recommend the use of β-blockers in patients with prior myocardial infarction (strength of evidence A [based on randomized controlled trials]), hypertension (strength of evidence B [based on cohort or case control studies]), and atrial fibrillation (strength of evidence B). Calcium-channel blockers are also recommended for patients with atrial fibrillation (strength of evidence C), angina (strength of evidence A), and hypertension (strength of evidence C).
This article provides an overview of HFPEF, its pathophysiology, diagnosis, and pharmacologic management. Clinical trials on the use of pharmacologic agents in managing the disease will be evaluated. Future perspectives for managing this disease state are also discussed.
Abstract and Introduction
Abstract
Objective: To provide an overview of heart failure with preserved ejection fraction (HFPEF), as well as its pathophysiology, diagnosis, and clinical evidence regarding its pharmacologic management.
Data Sources: Peer-reviewed articles were identified from MEDLINE, International Pharmaceutical Abstracts, and Current Contents (all 1966-August 2010) using the search terms heart failure with preserved ejection fraction, diastolic dysfunction, diastolic heart failure, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), digoxin, β-blockers, calcium-channel blockers, and vasodilators. Citations from available articles were also reviewed for additional references.
Study Selection and Data Extraction: Fourteen published manuscripts relating to pharmacologic management of HFPEF were identified.
Data Synthesis: The prevalence of HFPEF has continued to increase. Compared to heart failure with left ventricular systolic dysfunction, HFPEF has been largely understudied. Unlike in the management of heart failure with left ventricular systolic dysfunction, ACE inhibitors, ARBs, β-blockers, and aldosterone antagonists did not demonstrate mortality benefit in HFPEF, with the exception of one small study evaluating the use of propranolol. However, this study enrolled a small number of patients with recent history of myocardial infarction, which limited the generalizability of the results. Most of the current evidence centers on morbidity benefits and symptom reduction. One study showed that treatment with candesartan reduced hospital admissions in this population of patients. Management of HFPEF still focuses on optimally managing underlying diseases (eg, hypertension).
Conclusions: Much remains to be learned about the appropriate pharmacologic management of patients with HFPEF. Hypertension is in most cases the predominant contributor to its development and progression. For this reason, antihypertensive treatment, including ACE inhibitors, ARBs, β-blockers, and calcium-channel blockers, has been evaluated and is recommended to control the disease in this patient population, although these agents have not demonstrated significant benefit beyond blood pressure control. Further research into the pathophysiology of HFPEF may contribute to identifying the most optimal agent in managing this disease.
Introduction
Heart failure is caused primarily by systolic or diastolic dysfunction. Systolic dysfunction is defined as an abnormality in systolic contraction leading to a low left ventricular ejection fraction (LVEF). Diastolic dysfunction is defined as an abnormality of diastolic distentability, filling, or relaxation of the left ventricle, regardless of whether the LVEF is preserved. However, since diastolic dysfunction is difficult to measure, the distinction between these patient groups is characterized in terms of their LVEF. Patients with heart failure are divided into those with reduced or preserved ejection fraction. Operationally, heart failure with preserved ejection fraction (HFPEF) has been defined, according to the Framingham criteria, as LVEF >45% and the absence of mitral stenosis, pericardial disease, or noncardiac causes of dyspnea, edema, and fatigue. However, clinical studies that evaluated pharmacologic management for HFPEF have used LVEFs of ≥35%, ≥40%, ≥45%, or ≥50% as the definition of HFPEF.
The prevalence of HFPEF has increased over time, from approximately 37% in the 1980s to over 50% in the 2000s, among all patients presenting with acute decompensated heart failure. HFPEF carries a significant morbidity and mortality burden (5-year mortality rate 65%). Impaired renal function, New York Heart Association (NYHA) functional class III or IV, male sex, and older age are important predictors of mortality. Compared to patients with left ventricular systolic dysfunction, patients with HFPEF have better survival rates (mortality rate 68% vs 65%). However, in the past 2 decades, the prognosis has improved for patients with systolic heart failure but not with HFPEF. Management of HFPEF has been largely understudied. The most updated guidelines developed by the American Heart Association and American College of Cardiology (AHA/ACC) stated that in patients with HFPEF, physicians should be vigilant in controlling blood pressure, providing optimal coronary artery disease treatment, and controlling ventricular rate. Diuretics are recommended for controlling pulmonary congestion and peripheral edema. Unlike in systolic ventricular dysfunction, besides managing underlying risk factors, there are no specific pharmacotherapeutic recommendations for management of the disease itself, especially regarding improvement in mortality.
On the other hand, the most recent Heart Failure Society of America (HFSA) guidelines recommend that angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors may be considered in HFPEF in the absence of other specific indications. The strength of evidence for this recommendation, however, is only C, indicating that it is based on expert opinions. The guidelines also recommend the use of β-blockers in patients with prior myocardial infarction (strength of evidence A [based on randomized controlled trials]), hypertension (strength of evidence B [based on cohort or case control studies]), and atrial fibrillation (strength of evidence B). Calcium-channel blockers are also recommended for patients with atrial fibrillation (strength of evidence C), angina (strength of evidence A), and hypertension (strength of evidence C).
This article provides an overview of HFPEF, its pathophysiology, diagnosis, and pharmacologic management. Clinical trials on the use of pharmacologic agents in managing the disease will be evaluated. Future perspectives for managing this disease state are also discussed.
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