European Journal of Heart Failure

European Journal of Heart Failure 2001 3(2):243-248; doi:10.1016/S1388-9842(00)00153-7

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© 2001 European Society of Cardiology

Isolated diastolic heart failure as a cause of breathlessness in the community: the Arbroath study

Robert J. MacFadyen^a,b,*, Catherine M. MacLeod^a,b, Paul Shiels^a,b, W. Russell Smith^d and Thomas M. MacDonald^a,c

^a Department of Clinical Pharmacology and Therapeutics, University of Dundee, Ninewells Hospital and Medical School Dundee DD1 9SY, Scotland, UK
^b Department of Cardiology, University of Dundee, Ninewells Hospital and Medical School Dundee DD1 9SY, Scotland, UK
^c Medicines Monitoring Unit, University of Dundee, Ninewells Hospital and Medical School Dundee DD1 9SY, Scotland, UK
^d The Medical Centre Arbroath, Scotland, UK

^* Corresponding author. Cardiac Unit (7th Floor), Raigmore Hospital, Old Perth Road, Inverness IV2 3UJ, UK; tel.: +44-1463704000 ext. 5576, pager 7053; fax: +44-1463705463. E-mail address: robert.macfadyen{at}raigmore.scot.nhs.uk (R.J. MacFadyen).

	Abstract

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
The aim of this study was to examine the prevalence of exercise limitation due to diastolic heart failure among patients felt to have cardiac breathlessness by their general medical practitioner but not referred to hospital. We found that 18% of patients had a simple investigated profile compatible with isolated diastolic dysfunction as a cause of their symptoms. Symptoms appeared to pre-date major cardiac events (infarction; stroke; arrhythmia) that dominated the subsequent clinical course. The patients in this group have adverse cardiovascular risk profiles. Obesity was a common co-morbidity which may impair detailed 2-D echocardiographic assessment.

Key Words: Community-managed breathlessness • Diagnoses • Impaired exercise capacity • Diastolic heart failure

Received April 28, 1999; Revised December 15, 1999; Accepted December 20, 1999

	1. Introduction

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
Breathlessness due to isolated diastolic dysfunction or diastolic heart failure (impaired ventricular filling of whatever aetiology) remains controversial, and currently is mainly a diagnosis of exclusion [1]. Estimates of the prevalence of diastolic heart failure are few and confined to hospital populations [2,3], often based on echocardiographic indices alone. In this report, we chose to search in the community where we have previously characterised systolic cardiac dysfunction [4] with some success.

	2. Patients and methods

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
2.1. Patients
Patients were referred over a 12-month period for assessment of breathlessness from one medical practice (five practitioners) in the town of Arbroath, Scotland. They were referred if the general practitioner had felt the symptoms were cardiac in origin and had prescribed a diuretic (loop or thiazide) on the basis of pulmonary oedema as one component of the clinical problem. No patient had undergone recent hospital-based assessment (5 years) of their breathlessness. They were then sent an information sheet describing the aims and nature of hospital assessments and asked to reply giving their written consent to examination. The Tayside Committee on Medical Research and Ethics approved the protocol and information sheet prior to commencing recruitment.

2.2. Exclusion criteria: patients over 85 years or not in an ambulatory care setting
Of the 103 patients referred for assessment; 10 were excluded due to age >85 years and a non-ambulatory care setting. A total of 93 patients were invited to attend for one visit on current drug therapy. Of these, 67 patients replied and accepted the invitation to be assessed (no specific reasons were given by those refusing to attend). Patients underwent, in random order, the following investigations:

• full clinical history and physical examination (RJM);
  
• rest ECG; chest radiograph (independently reported) and spirometry (age- and gender-corrected);
  
• transthoracic echocardiography (HP Sonos 1500); and
  
• a modified Bruce treadmill exercise test was conducted to exhaustion (aiming for RQ>1; max. HR>90% predicted) with monitored expired gas analysis (Airspec QP9000; CaSE Scientific Instruments Biggin Hill, England); ECG (Marquette Case 16; Marquette Electronics Milwaukee WI) pulse oximetry (sPaO₂ diagnostics;) and immediate post-exercise visual analogue symptom (VAS) scoring for breathlessness (20 cm non-graded).
  

Following clinical assessment, individual cases were divided into six pre-determined categorical diagnostic groups on the basis of full investigational results. The diagnostic classifications were:

• systolic heart failure (history/exercise data and echo);
  
• valvular heart disease (history/exam/exercise data and echo);
  
• symptomatic myocardial ischaemia (history/exercise ECG data);
  
• obstructive pulmonary disease/cor pulmonale/parenchymal lung disease (history/PFT/exercise data and CXR);
  
• isolated diastolic heart failure (history/exercise data and echo); and
  
• no obvious cardiopulmonary cause for breathlessness (history/exam/exercise data and echo/PFT/CXR).
  

For a diagnosis of diastolic heart failure as a cause of symptoms, patients had to have exertional breathlessness, echocardiographic evidence of impaired ventricular filling, weight- and age-adjusted impaired exercise tolerance, and no other abnormality of respiratory or cardiac function, including no cardiac arrhythmia or electrocardiographic ischaemia on exercise.

	3. Results

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
3.1. Demography
A total of 67 patients (72% of those invited) accepted an invitation to attend for assessment (24 male; 66.9±8 years; 29.1±4 kg m^–2). There were a number of common clinical features among the whole group:

• current cigarette smokers or past history of smoking in 61/67 (91%);
  
• female gender in 42/67 (62.7%);
  
• hypertension [known (previous diagnosis) or documented at the time of study (seated in triplicate and subsequent ambulatory BP)] in 39/67 (58.2%); and
  
• obesity (BMI>30 kg m^–2) in 31/67 (46.2%).
  

At initial interview, 63/67 had some history of cardiovascular disease. Hypertension was present in 39 (30 known/9 not documented prior to this assessment). Chest-pain symptoms typical of myocardial ischaemia were evident in 17, and features of generalised atherosclerosis (PVD or claudication symptoms with arterial bruits) were present in 16. Evidence of structural heart disease, such as valve replacement/previously documented VSD or an undiagnosed ‘murmur’, was evident in 13. Seven patients presented in atrial fibrillation (two not previously documented and untreated). Four patients denied any symptomatic limitation or breathlessness and these four patients had no immediately obvious cardiac history.

Respiratory disease was evident on symptomatic inquiry [as daily or regular productive cough; sputum or wheeze on exertion; previous tuberculous disease (2) or partial pneumonectomy (1)] in 16/67 and generally confirmed by abnormal spirometry and CXR. These patients were shown to have exercise limitation due to such respiratory disease, and four of these patients also showed oxygen desaturation during exercise oximetry. One patient had a mass on chest radiology subsequently shown to be bronchogenic carcinoma.

3.2. Exercise testing (Table 1)
Patients with a negative medical history who showed no exercise limitation on the basis of gas exchange parameters (RQ>1.1; extrapolated maximal oxygen consumption >30 ml kg^–1 min^–1; Ve/VCO₂ slope <25) were regarded as having no abnormality, despite symptomatic complaint. Of the 67 patients, 54 attempted the modified Bruce ETT, with the results shown in Table 1. The remaining patients could not complete treadmill studies due to: severe PVD (2); severe osteoarthritis (2); morbid obesity (4); uncontrolled HBP 220/110 (1); significant aortic stenosis, estimated gradient 100 mm Hg (1); uncontrolled anxiety (1); severe cor pulmonale (1); or limiting hemiparesis (1).

View this table: [in this window] [in a new window]   Table 1 Results of maximal symptom limited treadmill exercise testing (n=54) and echocardiographya

 
3.3. Echocardiographic assessment (Table 1)
All patients had acceptable qualitative and quantitative echocardiographic images for limited studies of diastolic filling (pulsed Doppler transmitral flow indices), systolic contractility and valvular function. Increased calculated left-ventricular mass was evident in patients with systolic heart failure, valvular heart disease and isolated diastolic heart failure. Impaired ventricular filling was common in several diagnostic groups, and was not confined to the isolated diastolic heart-failure group alone.

3.4. Specific patient groups
3.4.1. No obvious cardiopulmonary cause
These patients complained of breathlessness and exercise limitation, despite having a normal age- and weight-corrected exercise capacity. They were the most common diagnostic group and had a number of common features. They were overweight (30±4 kg m^–2). Of 20 cases, 14 were identified as likely to have no cardiopulmonary abnormality on the basis of history alone (no relevant cardiac history of events or diagnoses, usually in combination with cyclical oedema). The remaining cases (6) had possible relevant clinical diagnoses from the history that were not supported by investigational abnormalities (i.e. 2 with a murmur yet echocardiographic assessment was normal; 4 had a normal exercise study). Three patients gave a history suggestive of primary respiratory disease but normal spirometry and CXR. Two patients had exertional chest pain typical of myocardial ischaemia but had a normal rest and stress ECG. One patient had a history of previous myocardial infarction, but no supporting documentation (not hospitalised), normal ECG, normal echocardiogram and exercise test. Exercise capacity was normal in all cases (extrapolated maximal oxygen capacity, EMOC=32–45 ml kg^–1 min^–1).

3.4.2. Diastolic heart failure
These patients (12/67) were those with symptomatic breathlessness and documented exercise limitation in the absence of lung disease; exercise inducible ischaemia or arrhythmia; a normal heart rate rise to exercise; and no valvular disease, but abnormal ventricular filling indices. The patients in this group were not identified on the basis of abnormal diastolic echo parameters alone, as these were common to most patients (including those with no exercise limitation) and appeared to be age-related, as expected (although no age correction was possible with these small numbers).

Patients in the diastolic heart failure group had a variety of common clinical characteristics:

• 10 of 12 had hypertension;
  
• 11 of 12 had a normal rest ECG (the one abnormal recording had inferior ST flattening);
  
• 6 of 12 had obesity (BMI >30);
  
• of 12 had cardiomegaly on chest radiograph; and
  
• 1 had small bilateral pleural effusions on CXR (not evident on clinical examination).
  

Thus, 12 of 67 patients (18%) from a community sample of breathless patients had exercise limitation and isolated diastolic filling abnormalities on echocardiography, suggestive of symptomatic diastolic heart failure. Patients were predominantly female, overweight and being treated for hypertension with echocardiographic left-ventricular hypertrophy. Accordingly, all had adverse cardiovascular risk profiles for future cardiac and vascular events.

	4. Discussion

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
Isolated diastolic heart failure remains a controversial clinical entity [1]. Many clinicians are unsatisfied with a diagnosis arrived at by exclusion, as a matter of principle, particularly where specific therapy for symptomatic diastolic dysfunction has not been clearly agreed. There is a basic confusion in the definition of this group of patients, and only very recently have consensus statements emerged regarding this topic. Their practical application is as yet untested.

Denying the existence of symptoms or the possibility of potential investigation seems unlikely to be a valuable exercise. We hypothesised that a cardiopulmonary cause can be ruled out within simple limits. While a number of processes can impair the filling and relaxation of the left ventricle, the link to exercise limitation is the key missing assessment. We tested these principles in this project.

While hospital populations are dominated by overt cardiac dysfunction, e.g. ischaemia, infarction, arrhythmia or valvular dysfunction, a great deal of cardiovascular pathology is managed in the community prior to index cardiac events. The qualitative characteristics of such patients, while they may resemble those in hospital practice, are not likely to be quantitatively similar. Having previously found it difficult to recruit symptomatic isolated diastolic heart failure for clinical trials or in emergency department surveys [3] we chose to extend our studies into community practice.

With respect to isolated diastolic heart failure, we assumed patients require: symptoms (most commonly exercise limitation and/or breathlessness on exertion); evidence of diastolic filling abnormalities (generally impaired simple transmitral Doppler indices); documented exercise limitation (at a formal exercise test); and no other obvious cause of these parameters, (most notably systolic or valvular dysfunction; ischaemia or arrhythmia). In this project, we used simple techniques that are available in any large hospital. We tried to avoid exhaustive diagnostic assessments and employed primary categorical diagnostic groups, accepting that some rare diagnoses may be missed at this level of investigation. While these are not exclusive (e.g. a patient with exercise-induced ischaemia might also have valvular disease), the two most significant groups, i.e. those with no cardiopulmonary cause and isolated diastolic heart failure, had no other anomalies. The characteristics, which separate these latter two groups, are simple echocardiographic anomalies, i.e. a prolonged E wave deceleration time, and documented exercise limitation on the basis of expired-gas analysis.

Simple transmitral Doppler indices can be achieved in a very high proportion of patients, particularly were obesity is common, as it was in this sample. We did not see pseudo-normalisation of the E/A ratio, or a restrictive filling pattern, which might be associated with more severe diastolic impairment. We did find enlargement of left atrial size [5].

It is not adequate for isolated echocardiographic indices and symptoms of breathlessness alone to be accepted as a diagnostic definition for isolated diastolic heart failure (IDF), unless there is demonstrable weight-corrected exercise limitation. Interestingly the IDF groups had higher perceived post-exercise breathlessness in terms of simple visual analogue symptom (VAS) than those with no obvious cardiopulmonary cause, their perceived breathlessness being comparable with patients with systolic dysfunction. Equally, the patients with overt respiratory disease had similar indices of diastolic relaxation as the diastolic heart-failure patients. This may, in part, relate to right ventricular pressure overload, with impairment of left ventricular filling due to ventricular interaction/interdependence [6].

As with systolic dysfunction, a number of pathological processes can underlie diastolic heart failure, e.g. ischaemia (which may be relative, e.g. in ventricular hypertrophy), restrictive cardiomyopathy, etc. Patients may have normal systolic function at rest that is abnormal during exercise stress (e.g. through ischaemia, valvular or chronotropic incompetence solely on exercise). We have not undertaken to analyse these options further, but the prevalence of hypertension and ventricular hypertrophy are obvious associations to microvascular and cellular ischaemia impairing the ability of the heart to respond appropriately to exercise [7].

The characteristics of the patients in the diastolic heart-failure group in this survey are interesting. The patients are younger than in previous hospital-based surveys [8]. The prevalence of hypertension and a normal resting ECG differ from those patients with overt systolic dysfunction. Symptomatic systolic failure seems to be rarely associated with a normal rest ECG [9] and hypertension generally disappears with the onset of significant systolic dysfunction. Exercise studies in hypertensive patients are uncommon, as patients are normally regarded as asymptomatic prior to the onset of myocardial ischaemia [10]. Clearly, this need not be the case. In this sample, echocardiographic ventricular hypertrophy was particularly common, and more so than in unselected hypertension [11].

Nearly all patients were at high risk of future cardiovascular events on the basis of conventional risk-factor clustering. The high prevalence of females is intriguing, as they are generally acknowledged to present later with coronary heart disease [12]. Alternatively, this may simply be a further example of the tendency to under-investigate the cardiovascular symptoms of women [13].

Obesity was notably prevalent in the sample as a whole and is powerfully associated with adverse cardiovascular outcomes [14]. Exercise capacity is limited in obesity. Weight-corrected definitions of exercise capacity [15], while somewhat nominal, can therefore stratify obesity as a cause of breathlessness. Many of this group had unremarkable investigations and were generally identifiable on the basis of symptoms and examination alone.

	References

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 

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2. Clarkson P.B., Wheeldon N.M., MacFadyen R.J., Pringle S.D., MacDonald T.M. Effects of brain natriuretic peptide on exercise hemodynamics and neurohormones in isolated diastolic heart failure. Circulation (1996) 93:2037–2042.[Abstract/Free Full Text]
3. Shiels P., Lim P.O., MacFadyen R.J., MacDonald T.M. Heart failure with normal systolic function. Br J Cardiol (1998) 5:533–536.
4. Wheeldon N.M., MacDonald T.M., Flucker C.J., et al. Echocardiography for chronic heart failure in the community. Q J Med (1993) 86:17–24.[Web of Science][Medline]
5. Clarkson P.B., Wheeldon N.M., Lim P.O., Pringle S.D., MacDonald T.M. Left atrial size and function: assessment using echocardiographic automated boundary detection. Br Heart J (1995) 74:664–670.[Abstract/Free Full Text]
6. Karunanthi M.K., Michniewicz J., Copeland S.E., Feneley M.P. Right ventricular preload recruitable stroke work, end systolic pressure volume and dP/dT_max end diastolic volume relations compared as indexes of right ventricular contractile performances in conscious dogs. Circulation (1992) 70:1179–1179.
7. Duncker D.J., Ishibashi Y., Bache R.J. Effect of treadmill exercise on transmural distribution of blood flow in hypertrophied left ventricle. Am J Physiol (1998) 275(4 Pt 2):H1274–H1282.[Web of Science][Medline]
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10. Lim P.O., MacFadyen R.J., Clarkson P.B.M., MacDonald T.M. Impaired exercise tolerance in hypertensive patients. Ann Int Med (1996) 124:41–55.[Abstract/Free Full Text]
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12. Swahn E. The care of patients with ischaemic heart disease from a gender perspective. Eur Heart J (1998) 19:1758–1765.[Free Full Text]
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