Skip Navigation

European Journal of Heart Failure 2004 6(2):125-136; doi:10.1016/j.ejheart.2003.11.002
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Thomas, M. D.
Right arrow Articles by Sutton, G. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thomas, M. D.
Right arrow Articles by Sutton, G. C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2003 European Society of Cardiology

The epidemiological enigma of heart failure with preserved systolic function

Martin D. Thomas*, Kevin F. Fox, Andrew J.S. Coats and George C. Sutton

Cardiovascular Medicine, National Heart and Lung Institute, Imperial College Charing Cross Campus, Fulham Palace Road, London SW3 6LY, UK

* Corresponding author. Tel.: +44-0-20-8846-7352; fax: +44-0-20-8383-5513. E-mail address: s.graves{at}imperial.ac.uk


   Abstract
Top
 Abstract
1. Introduction
 2. Conclusions
 References
 
Background: Current epidemiological evidence suggests that the prevalence of preserved systolic function in patients with heart failure varies widely from 13 to 74%. This inconsistency suggests a lack of consensus as to what this condition really is and how it has been characterised for epidemiological studies.

Aims: In this review, we summarise and discuss the current understanding of the epidemiology of heart failure with preserved systolic function and the challenges that this raises.

Methods: Studies were identified from Medline and Embase Literature Database searches using the subject headings heart failure, diastolic heart failure, epidemiology, incidence, prevalence, diagnosis, prognosis and mortality.

Results: Sixty-one studies of congestive heart failure with preserved systolic function were reviewed. There is great diversity in the criteria used to determine whether heart failure is present, the patient population, the setting of the study and methods of evaluating left ventricular function. This makes epidemiological studies of prevalence, morbidity and mortality impossible to compare.

Conclusions: The diagnosis of this syndrome might be better defined in terms of symptoms, elevated neuro hormones and impaired cardiac workload. This would allow accurate identification of cases so that further research could be conducted to measure outcome and assess therapeutic benefit.

Key Words: Heart failure • Preserved systolic function • Epidemiology

Received August 21, 2002; Revised September 16, 2003; Accepted November 13, 2003


   1. Introduction
Top
 Abstract
 1. Introduction
2. Conclusions
 References
 
The concept that heart failure could arise in the setting of preserved systolic function was identified in the early 1970s [1] and by the 1980s the syndrome of heart failure with preserved systolic function was well recognised. Epidemiological evidence suggests that the prevalence of preserved systolic function in patients with heart failure varies widely from 13 to 74% [2]. In these studies, patients presenting with heart failure and preserved systolic function are often deemed to have diastolic heart failure although few studies have directly assessed diastolic function. True diastolic heart failure may be present, but in the absence of abnormal diastolic function, there may be other cardiac abnormalities to explain the presenting symptoms including intermittent exercise-induced ischaemic dysfunction, valvular heart disease or left ventricular hypertrophy or an entirely non-cardiac cause.

The different populations studied and differences in the criteria used for the definition of heart failure in general and for diastolic heart failure in particular hamper the interpretation of epidemiological data. There is often lack of any objective physiological or biochemical evidence of cardiac dysfunction. This may have over-estimated the frequency of this important clinical syndrome. Clarification is required to allow accurate identification of this syndrome so that further research can be conducted to measure outcomes and assess therapeutic benefit.

In this review, we discuss the current understanding of the epidemiology of heart failure with preserved systolic function and the challenges that this raises.

1.1. Defining and identifying heart failure
1.1.1. Textbook definitions
Before defining heart failure with preserved systolic function, it is important to comment on the definition of heart failure itself. Many definitions [3–5] of heart failure are available in textbooks but these often concentrate on selective features of the condition. No single definition is entirely satisfactory but one that is often quoted is: ‘heart failure is a pathophysiological state in which an abnormality of cardiac function is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues’ [4]. However, this definition cannot be used in clinical practice, as heart failure is a clinical syndrome based on characteristic symptoms, findings on examination and the results of appropriate investigations although no single investigation can confirm or refute the diagnosis.

1.1.2. Scoring systems
Scoring systems have been developed to improve the accuracy of diagnosing heart failure and provide a standard for epidemiological studies and interventional trials [6,7]. Patient's symptoms, signs and investigations are scored and if the total score is greater than a predetermined number the patient is classified as having heart failure. In each of these there is no objective measurement of left ventricular function by echocardiography, cardiac catheterisation, magnetic resonance imaging or nuclear ventriculography.

Attempts have been made to validate the Framingham [6], Duke [8] and Boston [7] scores against left ventricular ejection fraction obtained at cardiac catheterisation or nuclear ventriculography. These scoring systems do not clearly differentiate between patients with a reduced ejection fraction from those with normal ejection fraction. The Framingham score has a sensitivity and specificity of 0.63 to predict an ejection fraction of ≤40%. Corresponding figures for sensitivity and specificity in the Duke score are 0.73 and 0.54 and for the Boston score 0.50 and 0.78 [9]. Such findings are inadequate when trying to identify patients with heart failure and preserved systolic function.

1.1.3. Guidelines for the diagnosis of heart failure
Guidelines for the diagnosis of heart failure have been proposed by the Task Force on Heart Failure of the European Society of Cardiology [10]. To meet the case definition of heart failure, patients must have appropriate symptoms (shortness of breath, fatigue, fluid retention or any combination of these symptoms) or clinical signs of fluid retention (pulmonary or peripheral) in the presence of an underlying abnormality of cardiac structure or function with a response to treatment if the diagnosis is in doubt. Echocardiography is recommended as the most practical tool to demonstrate cardiac dysfunction although no specific abnormalities are listed. These are clearly more helpful diagnostic criteria than previously utilised because they can be applied to patient populations. The discrepancy between such a clinical definition and previous scoring systems may explain differences in incidence rates of heart failure in population based studies [11–13].

1.1.4. Definitions used for therapeutic trials
In the major therapeutic trials for heart failure management [14–17] the definition of heart failure has been based on the presence of symptoms and signs of heart failure with an ejection fraction ≤35%. In the CONSENSUS Study [18] there was no assessment of left ventricular function and there may have been patients with preserved systolic function.

1.2. Defining heart failure with preserved systolic function
The definition of heart failure with preserved systolic function poses particular difficulties. Patients fulfilling the criteria for the diagnosis of heart failure but with preserved systolic function are often presumed to have diastolic heart failure but frequently there is no assessment of diastolic function. Heart failure with preserved systolic function is a different entity to heart failure with definite abnormalities of diastolic function and must be clearly distinguished. The assumption that a patient presenting with signs of heart failure and a ‘normal’ ejection fraction has diastolic heart failure may be misleading in clinical practice. Non-cardiac conditions such as pulmonary disease, obesity, anaemia and pregnancy can present with breathlessness and preserved systolic function. Circulatory overload including renal failure and excessive fluid overloading must be excluded before considering a diagnosis of heart failure with preserved systolic function.

Abnormal diastolic indices are seen with increasing age [19], in patients with hypertension [20], coronary artery disease [21], diabetes [22] and hypertrophic cardiomyopathy [23] and can be observed in asymptomatic subjects [24]. It has been suggested that there is a transition from asymptomatic diastolic abnormalities to the clinical syndrome of diastolic heart failure [20].

To fulfil the definition of diastolic heart failure patients should have the clinical syndrome of heart failure with preserved systolic function and have diastolic abnormalities.

In most studies of heart failure with preserved systolic function the cut off point for normal left ventricular ejection fraction is arbitrarily set between 35 and 45% whatever the imaging technique. Ejection fraction is normally distributed within the population and some people will lie outside the normal range (95% confidence interval) [25] and have no cardiac disease. Furthermore, a change in an individual patient's ejection fraction from 70 to 50% hardly represents ‘preservation’. Although left ventricular ejection fraction is used as a screening method to distinguish good from bad overall systolic pump function, it correlates poorly with symptoms and signs of heart failure [9]. Care must be taken for accurate measurements and left ventricular ejection fraction obtained by different techniques can differ substantially.

1.2.1. Assessment of diastolic function
The gold standard for assessing left ventricular diastolic function is often reported to be cardiac catheterisation with angiography [26–28]. Simultaneous measurement of pressure, volume and geometry can be made throughout the cardiac cycle. The rate of left ventricular pressure fall, the rate and timing of diastolic filling and diastolic compliance curves can be described. This procedure is invasive and impractical for the routine assessment of potential heart failure patients. Radionuclide ventriculography is less invasive and can provide measurements of peak-filling rate and filling fractions although full diastolic assessment cannot be made [29]. Doppler echocardiographic assessment of left ventricular filling patterns provides useful measures of diastolic function at the bedside. The clinical relevance of these measurements is well established in patients with chronic heart failure and correlates with symptoms, exercise limitation, response to therapy and prognosis [30–32]. There are limitations to this technique as transmitral Doppler flow is influenced by many factors including loading conditions of the left ventricle, heart rate, age of patient and operator technique [33–35] but it does provide a quick assessment of diastolic function if the limitations are recognised.

The apparent prevalence of diastolic dysfunction depends on which parameters of diastolic function are measured. The E/A ratio (peak early diastolic inflow velocity/peak late diastolic inflow velocity) is one of the most widely quoted indices of left ventricular diastolic filling but it may not be the optimum measure of diastolic abnormality. Caruana et al. observed a prevalence of primary diastolic dysfunction of 3–5% when using E/A ratio in association with deceleration time but this increased to 27% if isovolumic relaxation time was used [36]. Davie et al. assessed the prevalence of left ventricular filling abnormalities in patients with suspected heart failure and concluded that that the E/A ratio is almost useless for detecting the problem [37].

1.2.2. Guidelines on the diagnosis of diastolic heart failure
The European Study Group on diastolic heart failure has proposed a definition of diastolic heart failure [38]. This diagnosis requires three conditions to be satisfied simultaneously: (1) presence of signs or symptoms of congestive heart failure (exertional dyspnoea, orthopnoea, gallop sounds, lung crepitations, pulmonary oedema); (2) presence of normal or only mildly abnormal left ventricular systolic function (ejection fraction ≥45%); and (3) evidence of abnormal left ventricular relaxation, filling, diastolic distensibility or diastolic stiffness.

These guidelines have been criticised [39,40]. Vasan and Levy have proposed new criteria for diastolic heart failure with different levels of diagnostic certainty enabling a classification of definite, probable or possible diastolic heart failure [40]. To diagnose definite diastolic heart failure three criteria must be met: (1) definitive evidence of heart failure (clinical symptoms and signs and supporting laboratory tests); (2) objective evidence of normal left ventricular systolic function in proximity to the congestive heart failure event (EF >0.50 within 72 h of congestive heart failure event); and (3) objective evidence of left ventricular diastolic dysfunction at cardiac catheterisation. These guidelines are impractical for large population studies as an invasive assessment of left ventricular function within 72 h from the index event. In addition, Gandhi et al. [83] reports that only four of 29 patients with a left ventricular ejection fraction ≥45% 3–5 days after pulmonary oedema had a left ventricular ejection fraction <40% at the time of pulmonary oedema. The definition proposed by Vasan et al. would include patients with acute mitral or aortic regurgitation or purely mechanical causes of diastolic dysfunction such as mitral stenosis or constrictive pericarditis.

In contrast, the European guidelines allow for rapid non-invasive assessment of patients with possible diastolic heart failure, which can be performed in centres without invasive facilities and used for large epidemiological studies.

1.2.3. Definitions used for therapeutic trials
The ongoing PEP-CHF Study [41] is the first therapeutic trial to investigate patients with diastolic heart failure using specified criteria to define diastolic abnormalities based on the ESC guidelines rather than including patients by default on the presence of a ‘normal’ ejection fraction.

The lack of consensus on how to define diastolic heart failure, and how to diagnose it severely impairs our ability to perform and interpret epidemiological studies. This is reflected in the wide range of incidence and prevalence rates available from current epidemiological studies.

1.3. Epidemiology of heart failure with preserved systolic function
Sixty studies of congestive heart failure with preserved systolic function have been reviewed. These were identified from Medline and Embase Literature Database searches from January 1966 to December 2001 using the medical subject headings heart failure, diastolic heart failure, epidemiology, incidence, prevalence, diagnosis, prognosis and mortality and additional relevant references known to the authors. There is marked diversity in these studies in terms of the criteria used to determine whether heart failure was present, the patient population, the setting of the study, the method for evaluating left ventricular function and the criteria used to determine whether systolic function was normal and if diastolic function had been assessed.

Eleven (18%) are case studies (Table 1) and 49 (82%) are comparative studies where the prevalence of heart failure with preserved systolic function was determined from the total number of patients with heart failure (Table 2 shows data from the 41 studies of heart failure with preserved systolic function that had no assessment of diastolic function). In the majority of these studies, the clinical syndrome being described is that of heart failure with preserved systolic function as only eight studies directly assess diastolic function [42–49] (Table 3). The prevalence of heart failure with preserved systolic function varies considerably with a range of 13–75%.


View this table:
[in this window]
[in a new window]

  		Table 1 Case studies of patients with heart failure and preserved systolic function

 


View this table:
[in this window]
[in a new window]

  		Table 2 Comparative studies of patients with heart failure and preserved systolic function

 


View this table:
[in this window]
[in a new window]

  		Table 3 Comparative studies of patients with heart failure that include assessment of diastolic function

 
1.3.1. Selection criteria
Of the comparative studies, 13 were retrospective and 36 prospective. Forty-two studies had specific selection criteria and only eight could be considered truly unselected and population based [45,50–56]. Only two studies involved consecutive referrals to heart failure clinics [52,54]. In 16 cases, the selection criteria for patients entering the studies was not reported [46,48,49,53,57–68]. Five studies included patients referred for echocardiography [43,69–72] and four for radionuclide ventriculography [9,44,73,74]. Three studies only included men [75–77] and a further five only enrolled patients over the age of 65 [47,78–81]. Two only included patients with hypertension [82,83]. Another studied only patients with aortic stenosis [84] and another only survivors of myocardial infarction [85]. One only included patients with acute left ventricular failure [42], one only patients with coronary artery disease [86], one with patients known to have a history of myocardial infarction or hypertension [87], one with patients with New York Heart Association Class III/IV heart failure [88] and one only included patients referred to a geriatric clinic [89].

Eleven studies [1,100–105,107–109] were case series describing patients with heart failure with preserved systolic function with no assessment of diastolic function using specific selection criteria. Selection was based on the presence of hypertension [104,105,108,109], referral for cardiac catheterisation [1,101,103,106] or radionuclide ventriculography [102], digoxin therapy [107] or New York Heart Association Class III/IV heart failure [100] (Table 1).

1.3.2. Case definitions of heart failure
The case definitions for the diagnosis of heart failure were varied. In those studies where the Framingham criteria were used prevalence rates for heart failure with preserved systolic function ranged from 23 to 53% but when no set criteria were used rates varied from 14 to 74%. The wider spread of prevalence rates seen, when the Framingham criteria were not used reflects the broad range of case definitions used in these studies.

1.3.3. Assessment of left ventricular systolic function
The imaging technique used to assess left ventricular systolic function was echocardiography in 29, radionuclide ventriculography in 12 and radiographic left ventricular contrast angiography in one. In six studies there was a combination of imaging techniques employed. Two studies did not specify which technique was used [62,81]. Using echocardiography, preserved systolic function was seen in 28–75% cases whereas radionuclide ventriculography gave rates of 14–58%. Assessment of left ventricular function was performed at the time of symptoms in the majority of cases but the time interval for imaging varied.

1.3.4. Assessment of diastolic function
Diastolic function was only assessed in eight studies [42–49] (Table 3). When abnormalities of diastolic function are included there is a considerable reduction in the prevalence of true diastolic heart failure from heart failure with preserved systolic function although there is still a wide range of 6–51%.

Only one group has utilised the European Society of Cardiology guidelines on the diagnosis of diastolic heart failure which although currently only available as an abstract provides important information. Badano et al. [48] identified 133 consecutive patients with heart failure in sinus rhythm. Seventy (53%) had preserved systolic function with a left ventricular ejection fraction ≥45% and 29 (22%) fulfilled the criteria for isolated diastolic dysfunction.

1.3.5. Clinical features of heart failure with preserved systolic function
Clinical features associated with heart failure with preserved systolic function were addressed in 21 studies (Table 4). There is no uniformity in the clinical features associated with the syndrome of heart failure with preserved systolic function. Increasing age, female gender and hypertension are most commonly found although not in all studies.


View this table:
[in this window]
[in a new window]

  		Table 4 Studies addressing the clinical features associated with heart failure with preserved systolic function

 
It has been suggested that heart failure with preserved systolic function confers a better prognosis than heart failure with impaired systolic function in terms of morbidity and mortality. From the studies under review there is contradictory evidence on outcome (Table 5). Three studies report lower hospitalisation rates [60,62,78] but four studies [53,67,68,85] report no difference. One-year mortality rates varied widely from 1.3 to 28% although they are consistently lower than for those with heart failure and impaired systolic function. Several studies report that longer-term mortality is similar [47,53,54,60,67,77,85]. This may be due to patients with heart failure and preserved systolic function subsequently developing systolic heart failure.


View this table:
[in this window]
[in a new window]

  		Table 5 Studies assessing morbidity±mortality in patients with heart failure and preserved systolic function

 

   2. Conclusions
Top
 Abstract
 1. Introduction
 2. Conclusions
References
 
There is inconsistency regarding the prevalence, morbidity and mortality of heart failure with preserved systolic function on the basis of the current literature. The wide variation in study design, patient selection, the definition of preserved systolic function and the method used for assessing ventricular function make comparisons very difficult.

The lack of high quality data affects our current understanding of the epidemiology of the condition. If patients who do not have heart failure are included in epidemiological studies or therapeutic trials an increased prevalence and reduced mortality is recorded which results in a bias in therapeutic trials towards an improved outcome. Alternatively, if diastolic heart failure has an insidious onset, its incidence could be underestimated if patients fail to seek medical advice putting their symptoms of dyspnoea down to a general aging process [90]. The challenge for the epidemiologist is how to deal with these questions.

There is little doubt that within patients with dyspnoea and reduced systolic function there are those with a true disease process who respond to intervention with diuretics, ACE inhibitors and beta-blockers. If patients with dyspnoea and preserved systolic function benefit equally from pharmacological intervention with respect to morbidity and mortality, it is clinically irrelevant whether the diagnosis is heart failure with preserved systolic function or diastolic heart failure and supports the concept that this is a true pathophysiological entity. If patients do not have heart failure, their inclusion in studies of heart failure with preserved systolic function would explain their lower readmission, good prognosis and lack of evidence for pharmacological treatment benefit compared to a ‘normal’ population.

The case definition of heart failure with preserved systolic function needs to be improved. One way to achieve this would be to combine a consensus definition with markers of cardiac performance to standardize epidemiological studies.

All accepted criteria for diagnosing diastolic heart failure are defined at rest while symptoms occur with exertion. Improved echocardiographic imaging is now available which gives further information on diastolic function including long axis motion and tissue Doppler-imaging [91–93]. A combination of these techniques together with stress echocardiography might improve the assessment of the apparently normal heart giving further insight into ventricular function.

There is evidence that brain natriuretic peptide (BNP) levels are increased in patients with systolic and diastolic dysfunction [94–96] and such biochemical abnormalities could provide further evidence of an underlying disease process. Cardiopulmonary exercise testing with metabolic monitoring is an established method of assessing functional ability in heart failure and could be utilised in patients with heart failure with preserved systolic function [97].

The diagnosis of heart failure with preserved systolic function might be better separated from controversial echocardiographic parameters and defined in terms of symptoms, elevated neuro hormones and impaired cardiac workload capacity wherever possible supported by evidence of cardiac dysfunction at rest or on exertion.

There is a lack of consensus regarding the prevalence, morbidity and mortality of heart failure with preserved systolic function on the basis of the current literature. Only following such studies will be able to establish the true incidence of this condition in the community, characterize cases and establish its morbidity and mortality.


   Acknowledgements
 
We are very grateful to Professor David Wood, Dr Simon Gibbs, Dr Michael Henein and Professor Philip Poole-Wilson for their valuable contribution to the preparation of this manuscript.


   References
Top
 Abstract
 1. Introduction
 2. Conclusions
 References
 

  1. Dodek A, Kassebaum D.G, Bristow J.D. Pulmonary edema in coronary-artery disease without cardiomegaly. Paradox of the stiff heart. N Engl J Med (1972) 286:1347–1350.[Web of Science][Medline]
  2. Vasan R.S, Benjamin E.J, Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol (1995) 26:1565–1574.[Abstract]
  3. Wood P. Heart failure. In: Diseases of the heart and circulation—Wood P, ed. (1950) London: Eyre and Spottiswoode.
  4. Braunwald E. Heart failure: an overview. In: Heart failure—Fishma A, ed. (1977) New York: McGraw-Hill.
  5. Poole-Wilson P. Chronic heart failure causes pathophysiology, prognosis, clinical manifestations, investigation. In: Diseases of the heart—Julian D.G, Camm A.J, Fox K.M, Hall R.J.C, Poole-Wilson P, eds. (1989) London: Bailliere-Tindall. 48.
  6. McKee P.A, Castelli W.P, McNamara P.M, Kannel W.B. The natural history of congestive heart failure: the Framingham Study. N Engl J Med (1971) 285:1441–1446.[Web of Science][Medline]
  7. Carlson K, Lee D.C.S, Goroll A.H, Leahy M, Johnson R.A. An analysis of physicians reasons for prescribing long-term digitalis therapy in outpatients. J Chron Dis (1985) 38:733.[CrossRef][Web of Science][Medline]
  8. Harlan W, Oberman A, Grimm R, Rosatiet R.A. Chronic congestive heart failure in coronary artery disease: clinical criteria. Am Intern Med (1977) 86:133.
  9. Marantz P.R, Tobin J.N, Wassertheil-Smoller S, et al. The relationship between left ventricular systolic function and congestive heart failure diagnosed by clinical criteria. Circulation (1988) 77:607–612.[Abstract/Free Full Text]
  10. Guidelines for the diagnosis and treatment of chronic heart failure. Task Force for the diagnosis and treatment of chronic heart failure, European Society of Cardiology. Eur Heart J 2001;22:1527–1560.
  11. Ho K.K, Pinsky J.L, Kannel W.B, Levy D. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol (1993) 22(Suppl_A):6A–13A.[Medline]
  12. Cowie M.R, Wood D.A, Coats A.J, et al. Incidence and aetiology of heart failure: a population-based study. Eur Heart J (1999) 20:421–428.[Abstract/Free Full Text]
  13. Fox K, Cowie M.R, Wood D.A, et al. Coronary artery disease as the cause of incident heart failure in the population. Eur Heart J (2001) 22:228–236.[Abstract/Free Full Text]
  14. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med 1991;325:293–302.
  15. Packer M, Poole-Wilson P.A, Armstrong P.W, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation (1999) 100:2312–2318.[Abstract/Free Full Text]
  16. The cardiac insufficiency bisoprolol study II (CIBIS-II): a randomised trial. Lancet 1999; 353: 9–13.
  17. Packer M, Bristow M.R, Cohn J.N, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. US Carvedilol Heart Failure Study Group. N Engl J Med (1996) 334:1349–1355.[Abstract/Free Full Text]
  18. Effects of enalapril on mortality in severe congestive heart failure. Results of the cooperative north Scandinavian Enalapril survival study (CONSENSUS). The CONSENSUS Trial Study Group. N Engl J Med 1987;316:1429–1435.
  19. Iskandrian A, Hakki A. Age-related changes in left ventricular diastolic performance. Am Heart J (1986) 112:75–78.[CrossRef][Web of Science][Medline]
  20. Mandinov L, Eberli F.R, Seiler C, Hess O.M. Diastolic heart failure. Cardiovasc Res (2000) 45:813–825.[Abstract/Free Full Text]
  21. Bonow R.O, Bacharach S.L, Green M.V, et al. Impaired left ventricular diastolic filling in patients with coronary artery disease: assessment with radionuclide angiography. Circulation (1981) 64:315–323.[Abstract/Free Full Text]
  22. Nicolino A, Longobardi G, Furgi G, et al. Left ventricular diastolic filling in diabetes mellitus with and without hypertension. Am J Hypertens (1995) 8:382–389.[CrossRef][Web of Science][Medline]
  23. Maron B.J, Spirito P, Green K. Non-invasive assessment of left ventricular diastolic function by pulsed Doppler echocardiography in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol (1987) 10:733–742.[Abstract]
  24. Plotnick G.D. Changes in diastolic function-difficult to measure, harder to interpret. Am Heart J (1989) 118:637–641.[CrossRef][Web of Science][Medline]
  25. Gordon E.P, Schnittger I, Fitzgerald P.J, Williams P, Popp R.L. Reproducibility of left ventricular volumes by two-dimensional echocardiography. J Am Coll Cardiol (1983) 2:506–513.[Abstract]
  26. Mirsky I. Assessment of diastolic function: suggested methods and future considerations. Circulation (1984) 69:836–841.[Free Full Text]
  27. Walsh R. Evaluation of ventricular diastolic function using invasive techniques. Am J Cardiol Imaging (1990) 4:1–9.
  28. Little W, Downes T, Applegate R. Invasive evaluation of left ventricular diastolic performance. Herz (1990) 15:362–376.[Web of Science][Medline]
  29. Bonow R. Radionuclide angiographic evaluation of left ventricular diastolic function. Circulation (1991) 84:1208–1215.
  30. De Maria A, Wisenbaugh T. Identification and treatment of diastolic dysfunction: role of transmitral doppler recordings. J Am Coll Cardiol (1987) 9:1106–1107.[Web of Science][Medline]
  31. Douglas P.S. Diastolic dysfunction: old dog, new tricks. Am Heart J (1999) 137:777–778.[CrossRef][Web of Science][Medline]
  32. Brecker S.J.D, Gibson D.G. Echocardiographic evaluation of ventricular diastolic dysfunction: implications for treatment. Heart (1996) 76:386–387.[Free Full Text]
  33. Iwase M, Nagata K, Izawa H, et al. Age-related changes in left and right ventricular filling velocity profiles and their relationship in normal subjects. Am Heart J (1993) 126:419–426.[CrossRef][Web of Science][Medline]
  34. Fast J, Van Dam I, Heringa A, et al. Limits of reproducibility of mitral pulsed doppler spectra. Am J Cardiol (1988) 61:891–894.[CrossRef][Web of Science][Medline]
  35. Nishimura R, Abel M.D, Hatle L.K, Tajik A.J. Assessment of diastolic function of the heart: background and current applications of doppler echocardiography-II. Clinical studies. Mayo Clin Proc (1989) 64:181–204.[Web of Science][Medline]
  36. Caruana L, Davie A.P, Petrie M, McMurray J. Diagnosing heart failure. Eur Heart J (1999) 20:393.[Free Full Text]
  37. Davie A.P, Francis C.M, Caruana L, Sutherland G.R, McMurray J.J. The prevalence of left ventricular diastolic filling abnormalities in patients with suspected heart failure. Eur Heart J (1997) 18:981–984.[Abstract/Free Full Text]
  38. How to diagnose diastolic heart failure. European Study Group on diastolic heart failure. Eur Heart J 1998;19:990–1003.
  39. Brutsaert D.L. Diagnosing primary diastolic heart failure. Eur Heart J (2000) 21:94–96.[Free Full Text]
  40. Vasan R.S, Levy D. Defining diastolic heart failure: a call for standardized diagnostic criteria. Circulation (2000) 101:2118–2121.[Free Full Text]
  41. Cleland J.G, Tendera M, Adamus J, et al. Perindopril for elderly people with chronic heart failure: the PEP-CHF study. The PEP investigators. Eur J Heart Fail (1999) 1:211–217.[Abstract/Free Full Text]
  42. Stone G.W, Griffin B, Shah P.K, et al. Prevalence of unsuspected mitral regurgitation and left ventricular diastolic dysfunction in patients with coronary artery disease and acute pulmonary edema associated with normal or depressed left ventricular systolic function. Am J Cardiol (1991) 67:37–41.[CrossRef][Web of Science][Medline]
  43. Aguirre F.V, Pearson A.C, Lewen M.K, McCluskey M, Labovitz A.J. Usefulness of doppler echocardiography in the diagnosis of congestive heart failure. Am J Cardiol (1989) 63:1098–10102.[CrossRef][Web of Science][Medline]
  44. Soufer R, Wohlgelernter D, Vita N.A, et al. Intact systolic left ventricular function in clinical congestive heart failure. Am J Cardiol (1985) 55:1032–1036.[CrossRef][Web of Science][Medline]
  45. Yip G.W, Ho P.P, Woo K.S, Sanderson J.E. Comparison of frequencies of left ventricular systolic and diastolic heart failure in Chinese living in Hong Kong. Am J Cardiol (1999) 84:563–567.[CrossRef][Web of Science][Medline]
  46. Shiels P. Heart failure with normal systolic function. Br J Cardiol (1998) 5:533–536.
  47. Kupari M, Lindroos M, Livanainen A.M, Heikkila J, Tilvis R. Congestive heart failure in old age: prevalence, mechanisms and 4-year prognosis in the Helsinki Ageing Study. J Intern Med (1997) 241:387–394.[CrossRef][Web of Science][Medline]
  48. Badano L, Albanese M.C, Fresco C, et al. Prevalence of diastolic heart failure among patients admitted to hospital with congestive heart failure. Eur J Heart Fail (2000) 2(Suppl 2):72. Abstract.[Free Full Text]
  49. MacFadyen R.J, MacLeod C.M, Shiels P, Russell-Smith W, MacDonald T.M. Isolated diastolic heart failure as a cause of breathlessness in the community: the Arbroath study. Eur J Heart Fail (2001) 3:243–248.[Abstract/Free Full Text]
  50. Ghali J.K, Kadakia S, Cooper R.S, Liao Y.L. Bedside diagnosis of preserved vs. impaired left ventricular systolic function in heart failure. Am J Cardiol (1991) 67:1002–1006.[CrossRef][Web of Science][Medline]
  51. Bier A.J, Eichacker P.Q, Sinoway L.I, Terribile S.M, Strom J.A, Keefe D.L. Acute cardiogenic pulmonary edema: clinical and non-invasive evaluation. Angiology (1988) 39:211–218.[CrossRef][Web of Science][Medline]
  52. Caruana L, Petrie M.C, Davie A.P, McMurray J.J. Do patients with suspected heart failure and preserved left ventricular systolic function suffer from ‘diastolic heart failure’ or from misdiagnosis? A prospective descriptive study. Br Med J (2000) 321:215–218.[Abstract/Free Full Text]
  53. McDermott M.M, Feinglass J, Sy J, Gheorghiade M. Hospitalized congestive heart failure patients with preserved vs. abnormal left ventricular systolic function: clinical characteristics and drug therapy. Am J Med (1995) 99:629–635.[CrossRef][Web of Science][Medline]
  54. McAlister F.A, Teo K.K, Taher M, et al. Insights into the contemporary epidemiology and outpatient management of congestive heart failure. Am Heart J (1999) 138:87–94.[CrossRef][Web of Science][Medline]
  55. Madsen B.K, Videbaek R, Stokholm H, Mortensen L.S, Hansen J.F. Prognostic value of echocardiography in 190 patients with chronic congestive heart failure. A comparison with New York Heart Association functional classes and radionuclide ventriculography. Cardiology (1996) 87:250–256.[Web of Science][Medline]
  56. Vasan R.S, Larson M.G, Benjamin E.J, Evans J.C, Reiss C.K, Levy D. Congestive heart failure in subjects with normal vs. reduced left ventricular ejection fraction: prevalence and mortality in a population-based cohort. J Am Coll Cardiol (1999) 33:1948–1955.[Abstract/Free Full Text]
  57. Gardin J, Arnold A, Kitzman D. Congestive heart failure with preserved sytolic function in a large community-dwelling elderly cohort: The Cardiovascular Health Study. JACC (1995) (special issue):423A–424A.
  58. Wong W, Gold S, Fukuyama O, Blanchette P.L. Diastolic dysfunction in elderly patients with congestive heart failure. Am J Cardiol (1989) 63:1526–1528.[CrossRef][Web of Science][Medline]
  59. Mosterd A, Hoes A.W, de Bruyne M.C, et al. Prevalence of heart failure and left ventricular dysfunction in the general population: The Rotterdam Study. Eur Heart J (1999) 20:447–455.[Abstract/Free Full Text]
  60. Diller P.M, Smucker D.R, David B, Graham R.J. Congestive heart failure due to diastolic or systolic dysfunction. Frequency and patient characteristics in an ambulatory setting. Arch Fam Med (1999) 8:414–420.[Abstract/Free Full Text]
  61. Aronow W.S, Ahn C. Incidence of heart failure in 2737 older persons with and without diabetes mellitus. Chest (1999) 115:867–868.[Abstract/Free Full Text]
  62. Senni M, Tribouilloy C.M, Rodeheffer R.J, et al. Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation (1991) 98:2282–2289.
  63. Takarada A, Kurogane H, Minamiji K, et al. Congestive heart failure in the elderly-echocardiographic insights. Jpn Circ J (1992) 56:527–534.[Medline]
  64. Madsen B.K, Hansen J.F, Stokholm K.H, Brons J, Husum D, Mortensen L.S. Chronic congestive heart failure. Description and survival of 190 consecutive patients with a diagnosis of chronic congestive heart failure based on clinical signs and symptoms. Eur Heart J (1994) 15:303–310.[Abstract/Free Full Text]
  65. Cohen-Solal A, Desnos M, Delahaye F, Emeriau J.P, Hanania G. A national survey of heart failure in French hospitals. The Myocardiopathy and Heart Failure Working Group of the French Society of Cardiology, the National College of General Hospital Cardiologists and the French Geriatrics Society. Eur Heart J (2000) 21:763–769.[Abstract/Free Full Text]
  66. Ghali J.K, Kadakia S, Bhatt A, Cooper R, Liao Y. Survival of heart failure patients with preserved vs. impaired systolic function: the prognostic implication of blood pressure. Am Heart J (1992) 123:993–997.[CrossRef][Web of Science][Medline]
  67. McDermott M.M, Feinglass J, Lee P.I, et al. Systolic function, readmission rates, and survival among consecutively hospitalized patients with congestive heart failure. Am Heart J (1997) 134:728–736.[CrossRef][Web of Science][Medline]
  68. Dauterman K, Rowell R, Massie B. Congestive heart failure with preserved systolic function: mortality, readmission rates, and ACE inhibitor effect in a statewide sample of community hospitals. Circulation (1997) 96(Suppl I):I391.
  69. Kinney E.L, Wright R.J. Survival in patients with heart failure and normal basal systolic wall motion. Angiology (1989) 40:1025–1029.[CrossRef][Web of Science][Medline]
  70. Echeverria H.H, Bilsker M.S, Myerburg R.J, Kessler K.M. Congestive heart failure: echocardiographic insights. Am J Med (1983) 75:750–755.[CrossRef][Web of Science][Medline]
  71. Wheeldon N.M, MacDonald T.M, Flucker C.J, McKendrick A.D, McDevitt D.G, Struthers A.D. Echocardiography in chronic heart failure in the community. Q J Med (1993) 86:17–23.[Web of Science][Medline]
  72. Francis C.M, Caruana L, Kearney P, et al. Open access echocardiography in management of heart failure in the community. Br Med J (1995) 310:634–636.[Abstract/Free Full Text]
  73. Dougherty A.H, Naccarelli G.V, Gray E.L, Hicks C.H, Goldstein R.A. Congestive heart failure with normal systolic function. Am J Cardiol (1984) 54:778–782.[CrossRef][Web of Science][Medline]
  74. Bareiss P, Facello A, Constantinesco A, et al. Alterations in left ventricular diastolic function in chronic ischaemic heart failure. Assessment by radionuclide angiography. Circulation (1990) 81(2 Suppl):III71–III77.[Medline]
  75. Cohn J.N, Johnson G. Heart failure with normal ejection fraction. The V-HeFT Study. Veterans Administration Cooperative Study Group. Circulation (1990) 81(2 Suppl):III48–III53.[Medline]
  76. Cregler L.L, Georgiou D, Sosa I. Left ventricular diastolic dysfunction in patients with congestive heart failure. J Natl Med Assoc (1991) 83:49–52.[Medline]
  77. Taffet G.E, Teasdale T.A, Bleyer A.J, Kutka N.J, Luchi R.J. Survival of elderly men with congestive heart failure. Age Ageing (1992) 21:49–55.[Abstract/Free Full Text]
  78. Pernenkil R, Vinson J.M, Shah A.S, Beckham V, Wittenberg C, Rich M.W. Course and prognosis in patients (70 years of age with congestive heart failure and normal vs. abnormal left ventricular ejection fraction. Am J Cardiol (1997) 79:216–219.[CrossRef][Web of Science][Medline]
  79. Kitzman D.W, Gardin J.M, Gottdiener J.S, et al. Importance of heart failure with preserved systolic function in patients (65 years of age. CHS Research Group. Cardiovascular Health Study. Am J Cardiol (2001) 87:413–419.[CrossRef][Web of Science][Medline]
  80. Luchi R.J, Snow E, Luchi J.M, Nelson C.L, Pircher F.J. Left ventricular function in hospitalized geriatric patients. J Am Geriatr Soc (1982) 30:700–705.[Web of Science][Medline]
  81. Chen Y.T, Vaccarino V, Williams C.S, Butler J, Berkman L.F, Krumholz H.M. Risk factors for heart failure in the elderly: a prospective community-based study. Am J Med (1999) 106:605–612.[CrossRef][Web of Science][Medline]
  82. Iriarte M, Murga N, Sagastagoitia D, et al. Congestive heart failure from left ventricular diastolic dysfunction in systemic hypertension. Am J Cardiol (1993) 71:308–312.[CrossRef][Web of Science][Medline]
  83. Gandhi S.K, Powers J.C, Nomeir A.M, et al. The pathogenesis of acute pulmonary edema associated with hypertension. N Engl J Med (2001) 344:17–22.[Abstract/Free Full Text]
  84. Dineen E, Brent B.N. Aortic valve stenosis: comparison of patients with to those without chronic congestive heart failure. Am J Cardiol (1986) 57:419–422.[CrossRef][Web of Science][Medline]
  85. Warnowicz M.A, Parker H, Cheitlin M.D. Prognosis of patients with acute pulmonary edema and normal ejection fraction after acute myocardial infarction. Circulation (1983) 67:330–334.[Abstract/Free Full Text]
  86. Aronow W.S, Ahn C, Kronzon I. Prognosis of congestive heart failure in elderly patients with normal vs. abnormal left ventricular systolic function associated with coronary artery disease. Am J Cardiol (1990) 66:1257–1259.[CrossRef][Web of Science][Medline]
  87. Aronow W.S, Ahn C, Kronzon I. Normal left ventricular ejection fraction in older persons with congestive heart failure. Chest (1998) 113:867–869.[Abstract/Free Full Text]
  88. Duch A, Vidana T.R, Panicot J.E, de Miguel Diaz M.A, Cucto Y.F.B. Utilidad de la ecocardiografia en la insuficiencia cardiaca: estudio prospectivo sobre 100 pacientes. Med Clin (Barc) (1990) 95:641–643.[Medline]
  89. Cocchi A, Zuccala G, Del Sindaco D, Alimenti M, Menichelli P, Carbonin P.U. Cross-sectional echocardiography: a window on congestive heart failure in the elderly. Aging (Milano) (1991) 3:257–262.[Medline]
  90. Rogers A, Addington-Hall J.M, Abery A.J, et al. Knowledge and communication difficulties for patients with chronic heart failure: Qualitative Study. Br Med J (2000) 321:605–607.[Abstract/Free Full Text]
  91. Hatle L, Sutherland G.R. Regional myocardial function-a new approach. Eur Heart J (2000) 21:1337–1357.[Free Full Text]
  92. Alam M, Hoglund C. Assessment by echocardiogram of left ventricular diastolic function in healthy subjects using the atrioventricular palne displacement. J Am Coll Cardiol (1992) 69:565–568.
  93. Willenheimer R, Israelsson B, Cline C, Rydberg E, Broms K, Erhardt L. Left atrioventricular plane displacement is related to both systolic and diastolic left ventricular performance in patients with chronic heart failure. Eur Heart J (1999) 20:612–618.[Abstract/Free Full Text]
  94. Cowie M.R, Struthers A.D, Wood D.A, et al. Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care. Lancet (1997) 350:1349–1353.[CrossRef][Web of Science][Medline]
  95. McDonagh T.A, Robb S.D, Murdoch D.R, et al. Biochemical detection of left-ventricular systolic dysfunction. Lancet (1998) 351:9–13.[CrossRef][Web of Science][Medline]
  96. Lubien E, DeMaria A, Krishnaswamy P, et al. Utility of B-natriuretic peptide in detecting diastolic dysfunction: comparison with doppler velocity recordings. Circulation (2002) 105:595–601.[Abstract/Free Full Text]
  97. Florea V, Henein M.Y, Anker S.D, et al. Prognostic value of changes over time in exercise capacity and echocardiographic measurements in patients with chronic heart failure. Eur Heart J (2000) 21:146–153.[Abstract/Free Full Text]
  98. Bareiss P, Roul G, Facello A, et al. Congestive heart failure with intact systolic function. Arch Mal Coeur Vaiss (1991) 84:321–327.[Web of Science][Medline]
  99. Judge K.W, Pawitan Y, Caldwell J, Gersh B.J, Kennedy J.W. Congestive heart failure symptoms in patients with preserved left ventricular systolic function: analysis of the CASS registry. J Am Coll Cardiol (1991) 18:377–382.[Abstract]
  100. Brogan W.C, Hillis L.D, Flores E.D, Lange R. The natural history of isolated left ventricular diastolic dysfunction. Am J Med (1992) 92:627–630.[CrossRef][Web of Science][Medline]
  101. Setaro J.F, Soufer R, Remetz M.S, Perlmutter R.A, Zaret B.L. Long-term outcome in patients with congestive heart failure and intact systolic left ventricular performance. Am J Cardiol (1992) 69:1212–1216.[CrossRef][Web of Science][Medline]
  102. Kunis R, Greenberg H, Yeoh C.B, et al. Coronary revascularization for recurrent pulmonary edema in elderly patients with ischaemic heart disease and preserved ventricular function. N Engl J Med (1985) 313:1207–1210.[Web of Science][Medline]
  103. Topol E.J, Traill T.A, Fortuin N.J. Hypertensive hypertrophic cardiomyopathy of the elderly. N Engl J Med (1985) 312:277–283.[Abstract]
  104. Given B.D, Lee T.H, Stone P.H, Dzau V.J. Nifedipine in severely hypertensive patients with congestive heart failure and preserved ventricular systolic function. Arch Intern Med (1985) 145:281–285.[Abstract/Free Full Text]
  105. Kitzman D.W, Higginbotham M.B, Cobb F.R, Sheikh K.H, Sullivan M.J. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol (1991) 17:1065–1072.[Abstract]
  106. Forman D.E, Coletta D, Kenny D, et al. Clinical issues related to discontinuing digoxin therapy in elderly nursing home patients. Arch Intern Med (1991) 151:2194–2198.[Abstract/Free Full Text]
  107. Qirko S, Brokaj S, Popa Y. Incidence and clinical and echocardiographic characteristics of left ventricular insufficiency with normal systolic function in permanent arterial hypertension. Arch Mal Coeur Vaiss (1989) 82:1439–1442.[Web of Science][Medline]
  108. Zile M.R, Gaasch W.H, Carroll J.D, Feldman M.D. Heart failure with a normal ejection fraction: is measurement of diastolic function necessary to make the diagnosis of diastolic heart failure? Circulation (2001) 104:779–782.[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CMAJHome page
K. Tzanetos, D. Leong, and R. C. Wu
Office management of patients with diastolic heart failure
Can. Med. Assoc. J., March 3, 2009; 180(5): 520 - 527.
[Full Text] [PDF]

Home page
 ESC Textbook of Cardiovascular MedicineHome page
J. McMurray, M. Petrie, K. Swedberg, M. Komajda, S. Anker, and R. Gardner
CHAPTER 23 Heart Failure
ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Heart FailHome page
C. Adamopoulos, F. Zannad, R. Fay, A. Mebazaa, A. Cohen-Solal, L. Guize, Y. Juilliere, and F. Alla
Ejection fraction and blood pressure are important and interactive predictors of 4-week mortality in severe acute heart failure
Eur J Heart Fail, September 1, 2007; 9(9): 935 - 941.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Heart FailHome page
G. W. De Keulenaer and D. L. Brutsaert
Systolic and diastolic heart failure: Different phenotypes of the same disease?
Eur J Heart Fail, February 1, 2007; 9(2): 136 - 143.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
F. Bursi, S. A. Weston, M. M. Redfield, S. J. Jacobsen, S. Pakhomov, V. T. Nkomo, R. A. Meverden, and V. L. Roger
Systolic and diastolic heart failure in the community.
JAMA, November 8, 2006; 296(18): 2209 - 2216.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Heart FailHome page
J. J. Thune, C. Carlsen, P. Buch, M. Seibaek, H. Burchardt, C. Torp-Pedersen, L. Kober, and on behalf of the DIAMOND investigators
Different prognostic impact of systolic function in patients with heart failure and/or acute myocardial infarction
Eur J Heart Fail, August 1, 2005; 7(5): 852 - 858.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
P. Steendijk
Heart failure with preserved ejection fraction. Diastolic dysfunction, subtle systolic dysfunction, systolic-ventricular and arterial stiffening, or misdiagnosis?
Cardiovasc Res, October 1, 2004; 64(1): 9 - 11.
[Full Text] [PDF]

Home page
 Eur Heart JHome page
K. Dickstein
Appearances can deceive: even brave hearts can fail
Eur. Heart J., July 2, 2004; 25(14): 1181 - 1182.
[Full Text] [PDF]

Home page
 Journal of Renin-Angiotensin-Aldosterone SystemHome page
M. Tendera
The epidemiology of heart failure
Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1_suppl): S2 - S6.
[Abstract] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Thomas, M. D.
Right arrow Articles by Sutton, G. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thomas, M. D.
Right arrow Articles by Sutton, G. C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?