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HFNEF breathlessness: Is it really heart failure?
International Journal of Cardiology 143 (2010) 111–112
Contents lists available at ScienceDirect
International Journal of Cardiology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j c a r d
Editorial
HFNEF breathlessness: Is it really heart failure? Michael Henein a,b,⁎, Andrew Owen b,c a b c
Heart Centre and Department of Public Health and Clinical Medicine, Umeå University, Sweden Canterbury Christ Church University, UK Princess of Wales Hospital, UK
a r t i c l e
i n f o
Article history: Received 3 March 2010 Accepted 8 April 2010 Available online 2 May 2010 Keywords: HFNEF heart failure
The ancient Egyptians recognized the importance of the heart for life. Later Hippocrates again appreciated the value of the heart and postulated that it was the seat of life. He did not recognize heart failure as such but described signs and symptoms that can be interpreted as congestive heart failure. Two millennia later McKenzie diagnosed the syndrome of heart failure by the presence of a third heart sound. Subsequently, Paul Wood [1] in 1958 combined the stethoscope and the first imaging modality — the chest radiograph — to establish the diagnosis of heart failure. More recently, heart failure has been defined based mainly on a reduced left ventricular ejection fraction as assessed by left ventriculography. With the advent of echocardiography in the seventies, estimation of left ventricular ejection fraction by M-mode and 2D became the corner stone for diagnosing heart failure in breathless patients. Although ejection fraction has proved a useful clinical tool for assessing patient response to various treatment modalities, it does not accurately reflect exercise tolerance [2]. In the nineties, in an attempt to explain breathlessness in patients with maintained ejection fraction the concept of ‘diastolic heart failure’ was proposed and was summarized in a working group report [3]. The suggested diagnostic criteria, however, were too complicated for routine clinical use and failed to provide a clear physiological explanation of patient symptoms. Furthermore, they did not distinguish between age related physiological diastolic changes, the
⁎ Corresponding author. Heart Centre and Department of Public Health and Clinical Medicine, Umeå University, Sweden. Tel.: +46 907 852 652; fax: +46 901 137 633. E-mail addresses: [email protected], [email protected] (M. Henein). 0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.04.025
pathological diastolic disturbances associated with common diseases such as hypertension and diabetes and those of heart failure. To avoid the lack of clarity inherent in this concept of diastolic dysfunction as a cause for heart failure, the terms ‘Heart Failure with Normal Ejection Fraction’ — HFNEF [4] and ‘Heart Failure with Preserved Ejection Fraction’ — HFPEF [5] have emerged. These terms avoid reference to diastolic abnormalities and rely solely on the absence of reduced ejection fraction. The difficulty with this approach is that it includes a heterogeneous group of breathless patients, many of whom do not have heart failure, but have other causes for their symptoms such as COPD and obesity. It is not surprising therefore, that trials that recruited such patients failed to demonstrate a benefit from heart failure therapy e.g. ACE-Inhibitors [6] and A2 blockers [7]. A recent update by the European Working Group on the diagnosis of Diastolic Heart Failure has simplified the previously suggested criteria [8]. The diagnosis now relies on a modestly raised BNP and the use of the E/E′ ratio. BNP, although raised in heart failure, it also rises with increasing age (particularly in women), and is high in other comorbidities such as hypertension, coronary artery disease and atrial fibrillation, which are commonly present in breathless patients. No data are available on how BNP might best be used to identify patients with diastolic heart failure in the same way it does with systolic heart failure, perhaps because of the lack of a clear definition of diastolic heart failure. The E/E′ ratio has no physiological meaning and is simply a ratio of two velocities, both of which are likely to be deranged in a variety of conditions that affect cardiac function. Nevertheless, its relationship to LVEDP (end diastolic pressure) has been explored in highly selected patients (those with lung disease, coronary artery disease and atrial fibrillation were excluded) some 20 years younger than typical breathless patients [9]. A modest linear correlation between E/E′ and EDP, was found, r2 = 0.5 (p = 0.001). No information was provided on how accurate E/E′ is in identifying patients with an increased LVEDP, even in this group of unrepresentative patients. Furthermore, no data are available on the relationship between E/E′ and EDP in typical breathless patients, let alone the accuracy of E/E′ in identifying such patients with a raised LVEDP. Therefore, the proposed diagnostic criteria are based on conjecture rather than solid physiological principles and data. Consequently, the problem of misdiagnosing many predominantly elderly breathless patients with, for example lung disease and or obesity, as having heart failure remains. Thus, rather than replacing one unsatisfactory concept by another, a radical reappraisal of how these patients should be evaluated is called for. We propose a more clinically orientated approach. It should firstly
112
Editorial
be recognized that the patients in question are a heterogeneous group, where only a minority actually have heart failure. The challenge is to identify the patients with heart failure without the need for complex assessments. The syndrome of exertional breathlessness would be more appropriately described as exercise intolerance [10] (EXIT) rather than some form of heart failure. Clinical evaluation should be used to try and identify the organ system(s) responsible for the patient's symptoms. Respiratory breathlessness, for example, has characteristic features that are different from those due to cardiac causes. Heart failure does not cause hypoxia with exertion [11]. Therefore, patients who desaturate with exertion should have other causes for their symptoms investigated. Patients with obesity have an obvious cause for their symptoms. Patients with suspected cardiac EXIT should have a standard cardiological assessment (including an echocardiogram) that will identify whether coronary artery disease, atrial fibrillation with poor ventricular rate control, valve disease, congenital heart disease or pericardial disease are responsible for their symptoms. Patients in any of these categories should not be described as having heart failure with preserved ejection fraction. If, after a standard clinical assessment the patient's symptoms remain unexplained and cardiac EXIT is still suspected, a more detailed cardiac evaluation should be considered. This should focus on identifying a cardiac cause of breathlessness. There is uncertainty as to the exact cause of breathlessness in patients with heart failure, but various mechanisms have been proposed [10]. Patients with raised left atrial pressure resulting from an incompliant left ventricle (restrictive filling) may develop pulmonary congestion and breathlessness with exertion. Such patients are easily identified from the echocardiogram that shows a short left ventricular isovolumic relaxation time (b40 ms) and a high early filling velocity (E/A N 2) with a short deceleration time (b140 ms). These patients also typically have an enlarged left atrium. Patients who do not have a raised left atrial pressure at rest should undergo a stress echocardiogram to study the left ventricle at the time of symptoms, with particular attention to a reduction of cardiac output, which has been postulated to cause pulmonary hypoperfusion [11]. Patients with basal septal hypertrophy (a common finding in the elderly, particularly those with hypertension) may develop left ventricular outflow tract obstruction and consequently drop systolic blood pressure with stress at the time of symptoms [12]. Those with extensive coronary artery disease may develop impaired systolic function with stress. Occasionally patients may develop pulmonary hypertension with stress in the absence of raised left atrial pressure, suggesting a primary pulmonary cause for symptom development. The treatment of patients with cardiac EXIT therefore depends on the abnormality identified. For those with restrictive left ventricular filling a vasodilator e.g. ACE-Inhibitor or A2 blocker may reduce left atrial pressure and pulmonary venous pressure and hence symptomatic improvement [13]. For patients with dynamic outflow obstruction treatment with beta blockers [14] or verapamil is beneficial. Patients with extensive coronary artery disease who develop impaired systolic function with stress should be considered for revascularisation. Summary: The terms HFNEF and HFPEF are of limited value in describing exercise intolerance in breathless patients. They imply that heart failure is the underlying cause of the patient's symptoms, which in the majority is not. Rather, the general descriptive term of exercise intolerance (EXIT) would seem more appropriate. Basic clinical assessment should be used to identify the likely organ system
involved. For cardiac causes, a simple resting echocardiogram should identify potential mechanisms of EXIT in the majority of patients. A minority may require further investigation with a stress echocardiography. The foregoing should not be considered as recommendations or diagnostic criteria, but rather as a simple clinical approach to the breathless patient with a preserved left ventricular ejection fraction. Patients with EXIT constitute a heterogeneous group. Even the subgroup of patients with cardiac EXIT has a variety of causes for their symptoms. Previous attempts to define diastolic heart failure have been unsatisfactory because they have used general criteria to try and identify patients with quite different causes for their symptoms [3,8], or have been based on exclusion [4,5]. The term heart failure for such patients may be best avoided, with attention being focused on identifying the cause of the symptoms. Future clinical trials should identify a particular patient group for a putative treatment, if they are to have any chance of success.
Acknowledgment The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [15].
References [1] Wood P. The action of digitalis in heart failure with normal rhythm. Br Heart J 1940;2:132–40. [2] Duncan AM, Francis DP, Gibson DG, Henein MY. Limitation of exercise tolerance in chronic heart failure: distinct effects of left bundle-branch block and coronary artery disease. J Am Coll Cardiol 2004;43:1524–31. [3] European Study Group on Diastolic Heart Failure. How to diagnose diastolic heart failure. Eur Heart J 1998;19:990–1003. [4] Klapholz M, Maurer M, Lowe AM, New York Heart Failure Consortium, et al. Hospitalization for heart failure in the presence of a normal left ventricular ejection fraction: results of the New York Heart Failure Registry. J Am Coll Cardiol 2004;43:1432–8. [5] Borlaug BA, Melenovsky V, Russell SD, et al. Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation Nov 14 2006;114(20):2138–47 Electronic publication 2006 Nov 6. [6] Cleland JG, Tendera M, Adamus J, et al. The Perindopril in Elderly People with Chronic Heart Failure (PEP-CHF) study. Eur Heart J 2006;27:2338–45. [7] Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008:359. [8] Paulus WJ, Tschöpe C, Sanderson JE, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the heart failure and echocardiography associations of the European society of cardiology. Eur Heart J 2007;28:2539–50. [9] Kasner M, Westermann D, Steendijk P, et al. Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: a comparative Doppler-conductance catheterization study. Circulation 2007;116:637–47. [10] Kitzman DW, Groban L. Exercise intolerance. Heart Fail Clin 2008;4:99–115. [11] Sullivan M, Knight JD, Higginbotham Cobb FR. Relation between central and peripheral hemodynamics during stress in patients with chronic heart failure: muscle blood flow is reduced with maintenance of arterial perfusion pressure. Circulation 1989;80:769–81. [12] Henein MY, O'Sullivan CA, Coats AJS, et al. Stress induced left ventricular outflow tract obstruction — a potential cause of dyspnoea in the elderly. J Am Coll Cardiol 1997;30:1301–7. [13] Henein MY, Amadi A, O'Sullivan C, et al. ACE inhibition unmasks incoordinate diastolic wall motion in restrictive left ventricular disease. Heart 1996;76:326–31. [14] Al-Nasser F, Duncan A, Sharma R, et al. Beta-blocker therapy for dynamic leftventricular outflow tract obstruction. Int J Cardiol 2002;86:199–205. [15] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
Contents lists available at ScienceDirect
International Journal of Cardiology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j c a r d
Editorial
HFNEF breathlessness: Is it really heart failure? Michael Henein a,b,⁎, Andrew Owen b,c a b c
Heart Centre and Department of Public Health and Clinical Medicine, Umeå University, Sweden Canterbury Christ Church University, UK Princess of Wales Hospital, UK
a r t i c l e
i n f o
Article history: Received 3 March 2010 Accepted 8 April 2010 Available online 2 May 2010 Keywords: HFNEF heart failure
The ancient Egyptians recognized the importance of the heart for life. Later Hippocrates again appreciated the value of the heart and postulated that it was the seat of life. He did not recognize heart failure as such but described signs and symptoms that can be interpreted as congestive heart failure. Two millennia later McKenzie diagnosed the syndrome of heart failure by the presence of a third heart sound. Subsequently, Paul Wood [1] in 1958 combined the stethoscope and the first imaging modality — the chest radiograph — to establish the diagnosis of heart failure. More recently, heart failure has been defined based mainly on a reduced left ventricular ejection fraction as assessed by left ventriculography. With the advent of echocardiography in the seventies, estimation of left ventricular ejection fraction by M-mode and 2D became the corner stone for diagnosing heart failure in breathless patients. Although ejection fraction has proved a useful clinical tool for assessing patient response to various treatment modalities, it does not accurately reflect exercise tolerance [2]. In the nineties, in an attempt to explain breathlessness in patients with maintained ejection fraction the concept of ‘diastolic heart failure’ was proposed and was summarized in a working group report [3]. The suggested diagnostic criteria, however, were too complicated for routine clinical use and failed to provide a clear physiological explanation of patient symptoms. Furthermore, they did not distinguish between age related physiological diastolic changes, the
⁎ Corresponding author. Heart Centre and Department of Public Health and Clinical Medicine, Umeå University, Sweden. Tel.: +46 907 852 652; fax: +46 901 137 633. E-mail addresses: [email protected], [email protected] (M. Henein). 0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.04.025
pathological diastolic disturbances associated with common diseases such as hypertension and diabetes and those of heart failure. To avoid the lack of clarity inherent in this concept of diastolic dysfunction as a cause for heart failure, the terms ‘Heart Failure with Normal Ejection Fraction’ — HFNEF [4] and ‘Heart Failure with Preserved Ejection Fraction’ — HFPEF [5] have emerged. These terms avoid reference to diastolic abnormalities and rely solely on the absence of reduced ejection fraction. The difficulty with this approach is that it includes a heterogeneous group of breathless patients, many of whom do not have heart failure, but have other causes for their symptoms such as COPD and obesity. It is not surprising therefore, that trials that recruited such patients failed to demonstrate a benefit from heart failure therapy e.g. ACE-Inhibitors [6] and A2 blockers [7]. A recent update by the European Working Group on the diagnosis of Diastolic Heart Failure has simplified the previously suggested criteria [8]. The diagnosis now relies on a modestly raised BNP and the use of the E/E′ ratio. BNP, although raised in heart failure, it also rises with increasing age (particularly in women), and is high in other comorbidities such as hypertension, coronary artery disease and atrial fibrillation, which are commonly present in breathless patients. No data are available on how BNP might best be used to identify patients with diastolic heart failure in the same way it does with systolic heart failure, perhaps because of the lack of a clear definition of diastolic heart failure. The E/E′ ratio has no physiological meaning and is simply a ratio of two velocities, both of which are likely to be deranged in a variety of conditions that affect cardiac function. Nevertheless, its relationship to LVEDP (end diastolic pressure) has been explored in highly selected patients (those with lung disease, coronary artery disease and atrial fibrillation were excluded) some 20 years younger than typical breathless patients [9]. A modest linear correlation between E/E′ and EDP, was found, r2 = 0.5 (p = 0.001). No information was provided on how accurate E/E′ is in identifying patients with an increased LVEDP, even in this group of unrepresentative patients. Furthermore, no data are available on the relationship between E/E′ and EDP in typical breathless patients, let alone the accuracy of E/E′ in identifying such patients with a raised LVEDP. Therefore, the proposed diagnostic criteria are based on conjecture rather than solid physiological principles and data. Consequently, the problem of misdiagnosing many predominantly elderly breathless patients with, for example lung disease and or obesity, as having heart failure remains. Thus, rather than replacing one unsatisfactory concept by another, a radical reappraisal of how these patients should be evaluated is called for. We propose a more clinically orientated approach. It should firstly
112
Editorial
be recognized that the patients in question are a heterogeneous group, where only a minority actually have heart failure. The challenge is to identify the patients with heart failure without the need for complex assessments. The syndrome of exertional breathlessness would be more appropriately described as exercise intolerance [10] (EXIT) rather than some form of heart failure. Clinical evaluation should be used to try and identify the organ system(s) responsible for the patient's symptoms. Respiratory breathlessness, for example, has characteristic features that are different from those due to cardiac causes. Heart failure does not cause hypoxia with exertion [11]. Therefore, patients who desaturate with exertion should have other causes for their symptoms investigated. Patients with obesity have an obvious cause for their symptoms. Patients with suspected cardiac EXIT should have a standard cardiological assessment (including an echocardiogram) that will identify whether coronary artery disease, atrial fibrillation with poor ventricular rate control, valve disease, congenital heart disease or pericardial disease are responsible for their symptoms. Patients in any of these categories should not be described as having heart failure with preserved ejection fraction. If, after a standard clinical assessment the patient's symptoms remain unexplained and cardiac EXIT is still suspected, a more detailed cardiac evaluation should be considered. This should focus on identifying a cardiac cause of breathlessness. There is uncertainty as to the exact cause of breathlessness in patients with heart failure, but various mechanisms have been proposed [10]. Patients with raised left atrial pressure resulting from an incompliant left ventricle (restrictive filling) may develop pulmonary congestion and breathlessness with exertion. Such patients are easily identified from the echocardiogram that shows a short left ventricular isovolumic relaxation time (b40 ms) and a high early filling velocity (E/A N 2) with a short deceleration time (b140 ms). These patients also typically have an enlarged left atrium. Patients who do not have a raised left atrial pressure at rest should undergo a stress echocardiogram to study the left ventricle at the time of symptoms, with particular attention to a reduction of cardiac output, which has been postulated to cause pulmonary hypoperfusion [11]. Patients with basal septal hypertrophy (a common finding in the elderly, particularly those with hypertension) may develop left ventricular outflow tract obstruction and consequently drop systolic blood pressure with stress at the time of symptoms [12]. Those with extensive coronary artery disease may develop impaired systolic function with stress. Occasionally patients may develop pulmonary hypertension with stress in the absence of raised left atrial pressure, suggesting a primary pulmonary cause for symptom development. The treatment of patients with cardiac EXIT therefore depends on the abnormality identified. For those with restrictive left ventricular filling a vasodilator e.g. ACE-Inhibitor or A2 blocker may reduce left atrial pressure and pulmonary venous pressure and hence symptomatic improvement [13]. For patients with dynamic outflow obstruction treatment with beta blockers [14] or verapamil is beneficial. Patients with extensive coronary artery disease who develop impaired systolic function with stress should be considered for revascularisation. Summary: The terms HFNEF and HFPEF are of limited value in describing exercise intolerance in breathless patients. They imply that heart failure is the underlying cause of the patient's symptoms, which in the majority is not. Rather, the general descriptive term of exercise intolerance (EXIT) would seem more appropriate. Basic clinical assessment should be used to identify the likely organ system
involved. For cardiac causes, a simple resting echocardiogram should identify potential mechanisms of EXIT in the majority of patients. A minority may require further investigation with a stress echocardiography. The foregoing should not be considered as recommendations or diagnostic criteria, but rather as a simple clinical approach to the breathless patient with a preserved left ventricular ejection fraction. Patients with EXIT constitute a heterogeneous group. Even the subgroup of patients with cardiac EXIT has a variety of causes for their symptoms. Previous attempts to define diastolic heart failure have been unsatisfactory because they have used general criteria to try and identify patients with quite different causes for their symptoms [3,8], or have been based on exclusion [4,5]. The term heart failure for such patients may be best avoided, with attention being focused on identifying the cause of the symptoms. Future clinical trials should identify a particular patient group for a putative treatment, if they are to have any chance of success.
Acknowledgment The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [15].
References [1] Wood P. The action of digitalis in heart failure with normal rhythm. Br Heart J 1940;2:132–40. [2] Duncan AM, Francis DP, Gibson DG, Henein MY. Limitation of exercise tolerance in chronic heart failure: distinct effects of left bundle-branch block and coronary artery disease. J Am Coll Cardiol 2004;43:1524–31. [3] European Study Group on Diastolic Heart Failure. How to diagnose diastolic heart failure. Eur Heart J 1998;19:990–1003. [4] Klapholz M, Maurer M, Lowe AM, New York Heart Failure Consortium, et al. Hospitalization for heart failure in the presence of a normal left ventricular ejection fraction: results of the New York Heart Failure Registry. J Am Coll Cardiol 2004;43:1432–8. [5] Borlaug BA, Melenovsky V, Russell SD, et al. Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation Nov 14 2006;114(20):2138–47 Electronic publication 2006 Nov 6. [6] Cleland JG, Tendera M, Adamus J, et al. The Perindopril in Elderly People with Chronic Heart Failure (PEP-CHF) study. Eur Heart J 2006;27:2338–45. [7] Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008:359. [8] Paulus WJ, Tschöpe C, Sanderson JE, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the heart failure and echocardiography associations of the European society of cardiology. Eur Heart J 2007;28:2539–50. [9] Kasner M, Westermann D, Steendijk P, et al. Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: a comparative Doppler-conductance catheterization study. Circulation 2007;116:637–47. [10] Kitzman DW, Groban L. Exercise intolerance. Heart Fail Clin 2008;4:99–115. [11] Sullivan M, Knight JD, Higginbotham Cobb FR. Relation between central and peripheral hemodynamics during stress in patients with chronic heart failure: muscle blood flow is reduced with maintenance of arterial perfusion pressure. Circulation 1989;80:769–81. [12] Henein MY, O'Sullivan CA, Coats AJS, et al. Stress induced left ventricular outflow tract obstruction — a potential cause of dyspnoea in the elderly. J Am Coll Cardiol 1997;30:1301–7. [13] Henein MY, Amadi A, O'Sullivan C, et al. ACE inhibition unmasks incoordinate diastolic wall motion in restrictive left ventricular disease. Heart 1996;76:326–31. [14] Al-Nasser F, Duncan A, Sharma R, et al. Beta-blocker therapy for dynamic leftventricular outflow tract obstruction. Int J Cardiol 2002;86:199–205. [15] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.