European Journal of Heart Failure

European Journal of Heart Failure 2004 6(4):427-431; doi:10.1016/j.ejheart.2004.02.006

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© 2004 European Society of Cardiology

Diastolic heart failure. Paroxysmal or chronic?

Prithwish Banerjee^*, Andrew L. Clark, Nikolay Nikitin and John G.F. Cleland

Department of Cardiology, University of Hull, Castle Hill Hospital Kingston upon Hull HU16 5JQ, UK

^* Corresponding author. Tel.: +44-1482-624087; fax: +44-1482-624085. E-mail address: pbanerjee{at}ukonline.co.uk

	Abstract

Top Abstract 1. Introduction 2. Is it really... 3. Is it heart... 4. Diastolic heart failure... 5. Conclusions References

 
Heart failure with preserved systolic function is considered by some to be synonymous with diastolic heart failure (DHF). Although recent epidemiological studies have suggested that DHF constitutes 30–50% of all patients with heart failure, many cardiologists dealing with ambulant heart failure patients on a daily basis find that the vast majority of heart failure patients have systolic dysfunction. What could be the reasons for this? Referral bias and varying diagnostic thresholds and interpretation of results could be one important reason. Heart failure with preserved systolic function comprises a heterogeneous group of conditions: whilst some patients may truly have DHF, others may have heart failure due to subtle systolic dysfunction (noted on tissue Doppler imaging of the left ventricular long axis). Other patients actually have pulmonary disease, obesity or ischaemic heart disease, and have their symptoms attributed to ‘diastolic heart failure’ on the basis of ‘abnormal’ mitral diastolic flow indices that may, in fact, simply reflect aging. True DHF may be much less prevalent than suggested. A further possibility is that heart failure in patients with diastolic dysfunction might be paroxysmal rather than chronic. This group of patients may present predominantly to acute units like accident and emergency, coronary care units and intensive care units and are, therefore unlikely to figure prominently in the usual outpatient population of chronic systolic left ventricular dysfunction.

Key Words: LV, left ventricular • DHF, diastolic heart failure • LVH, left ventricular hypertrophy • SBP, systolic blood pressure • LVEDP, left ventricular end diastolic pressure • HFPSF, heart failure with preserved systolic function

Received March 26, 2003; Revised February 16, 2004; Accepted February 23, 2004

	1. Introduction

Top Abstract 1. Introduction 2. Is it really... 3. Is it heart... 4. Diastolic heart failure... 5. Conclusions References

 
Although epidemiological studies have suggested that 30–50% of heart failure patients have preserved left ventricular (LV) systolic function, the presumption that all of these patients have isolated diastolic heart failure (DHF) is unlikely to be correct [1]. Indeed, it has been argued that patients with preserved LV systolic function and symptoms suggestive of heart failure are frequently misdiagnosed since they often have other reasons for their symptoms such as obesity, pulmonary disease or myocardial ischaemia [2].

The current lack of standardised, reliable and easily applicable diagnostic criteria or a positive, all encompassing definition of DHF [3] is a key factor limiting accurate assessment of the prevalence of this condition. Ongoing trials of DHF [3] will clarify concerns about the outlook of DHF patients with respect to long term mortality [4,5] recurrent hospitalisation [4,5] and cost of care [6].

	2. Is it really diastolic heart failure?

Top Abstract 1. Introduction 2. Is it really... 3. Is it heart... 4. Diastolic heart failure... 5. Conclusions References

 
Recent studies [7,8] have found that in patients with presumed DHF and left ventricular hypertrophy (LVH), subtle abnormalities of LV systolic function are often present as measured by myocardial tissue Doppler imaging of the left ventricular long axis. Other studies have also reported similar findings [9,10]. This implies that a number of patients labelled as having DHF may not have true DHF; abnormal systolic long axis function is missed on routine 2-dimensional and M-mode echocardiography. The group of patients with clinical heart failure, diastolic dysfunction and mild systolic impairment may be in the middle of a spectrum of heart failure patients, with undetectable or incipient systolic abnormalities and obviously abnormal LV systolic function forming either ends of the spectrum [7].

	3. Is it heart failure at all?

Top Abstract 1. Introduction 2. Is it really... 3. Is it heart... 4. Diastolic heart failure... 5. Conclusions References

 
Epidemiological studies of DHF (Table 1) have suggested a significant prevalence and an adverse prognosis for the condition. A recently published cross-sectional survey [11] of 2042 randomly selected, 45 years or older residents of Olmstead county, Minnesota has even provided information on the prevalence of preclinical diastolic dysfunction in the community. Rigorous Doppler echocardiographic criteria were applied in this population to assess the prevalence of preclinical diastolic and systolic dysfunction as well as the prevalence of congestive heart failure. Another objective was to determine if diastolic dysfunction is predictive of all cause mortality. 2.2% of the population had clinically validated congestive heart failure (CHF), 44% of whom had preserved LV systolic function (LVEF>50%). Moderate or severe diastolic dysfunction with normal LVEF was present in 5.6% of the population suggesting that preclinical diastolic dysfunction is common. Less than half of those with moderate or severe diastolic dysfunction had recognized CHF. All grades of diastolic dysfunction, which were often not associated with CHF, were associated with a marked increase in all-cause mortality.

View this table: [in this window] [in a new window]   Table 1 Recent epidemiological studies of heart failure showing prevalence and prognosis of heart failure with preserved systolic function (HFPSF), presumed to have DHF

 
However, not all studies of DHF have come to the same conclusions. In a small study to assess the prevalence of isolated DHF in the community, MacFayden et al. [12] found that only 18% of the 67 patients referred with shortness of breath by primary care physicians in Arbroath, Scotland had DHF as a cause of their breathlessness. For isolated DHF to be diagnosed as a cause of symptoms, the 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. When strict criteria for diagnosing DHF were applied, the prevalence of DHF was found to be much lower than reported from some epidemiological studies [1].

Caruana et al. [2] in Glasgow, Scotland studied 109 patients referred by general practitioners for suspected heart failure who were subsequently found to have preserved LV systolic function. The aim was to determine whether these patients had other potential causes for their symptoms, rather than being diagnosed with diastolic heart failure. Of these 109, 40 were obese, 54 had obstructive airways disease diagnosed by spirometry and 33 either had a history of angina or myocardial infarction or had undergone a coronary artery bypass graft. Only seven patients lacked a recognized explanation for their symptoms. The study concluded that for most patients with heart failure and preserved systolic function an alternative diagnosis other than DHF is present to explain the symptoms. However, only E/A ratio on mitral inflow Doppler echocardiography was used to establish or exclude diastolic dysfunction in this study.

The paper in the present issue from Wales [13] suggests that there is no difference in left ventricular filling on echocardiography between an appropriate reference population and patients with breathlessness. Many breathless patients, particularly those with a past history of heart disease, are prone to be labelled as having diastolic heart failure, and yet have left ventricular filling indices in the normal range.

	4. Diastolic heart failure MAY BE acute heart failure

Top Abstract 1. Introduction 2. Is it really... 3. Is it heart... 4. Diastolic heart failure... 5. Conclusions References

 
The experience of many cardiologists dealing with chronic heart failure patients on a daily basis in ambulant outpatients does not tally with the expected high numbers of DHF patients suggested by hospital based epidemiological studies. Since most chronic heart failure patients apparently have LV systolic dysfunction, disbelief is often expressed at the existing data and isolated DHF has become a controversial clinical subject [14]. While one explanation for this discrepancy between observed and expected numbers is that DHF often progresses to systolic heart failure, another possibility is that isolated DHF might present predominantly as acute heart failure which resolves rapidly in response to therapy. It would thus not figure prominently in the population of chronic heart failure patients who are intermittently hospitalised with peripheral fluid overload and who predominantly have systolic heart failure. The natural history of a great number of primary DHF patients may be that of recurrent pulmonary oedema leading to a chronic congestive state only late in the course of the disease.

Of course, acute heart failure with preserved LV systolic function may have causes other than DHF (Table 2). Transient systolic dysfunction and transient mitral regurgitation have been sited as important causes. However, a recent study by Gandhi et al. [15] of 38 hypertensive patients with pulmonary oedema revealed a low prevalence of LV systolic dysfunction and no mitral regurgitation (MR) during the acute episode and on subsequent follow-up, suggesting that exacerbation of diastolic dysfunction and not transient LV systolic dysfunction or acute MR was responsible for heart failure at least in this group of patients.

View this table: [in this window] [in a new window]   Table 2 Causes of acute heart failure with preserved LV systolic function

 
A sudden severe rise in blood pressure (acute pressure overload), over-vigorous intravenous fluid therapy (acute volume overload) or marked tachycardia (mostly atrial fibrillation) can all result in acute heart failure in the presence of normal LV systolic function. This becomes more likely if LV diastolic function is impaired. Marked increase in systolic arterial blood pressure (SBP) causes impairment of diastolic function leading to flash pulmonary oedema [16]. Lowering of the arterial pressure produces a rapid resolution of the pulmonary oedema. Many elderly subjects and patients with LVH or hypertension have Doppler echocardiographic evidence of diastolic dysfunction but no symptoms or signs of heart failure at rest [17–19]. In these patients, rapid increase in SBP above 200 mm of Hg, for any reasons could precipitate pulmonary oedema in the presence of normal LV systolic function [20]. This might happen as a result of poor blood pressure control, underlying renal artery stenosis [21] or a hypertensive response to pain or stress. Pulmonary oedema could also be precipitated by the onset of tachyarrhythmias (especially atrial fibrillation), an increase in preload (e.g. IV fluids post surgery) [22] or vigorous exercise, especially if the exercise is associated with a hypertensive BP response [23–25].

Heart failure associated with preserved systolic function is predominantly a disease of elderly women, most of whom have hypertension [26]. Approximately 60% of patients with heart failure and preserved LV systolic function have hypertension [27]. Hypertensive heart failure manifests initially as recurrent pulmonary oedema and later in the course of the disease as congestive heart failure. DHF in hypertensives is therefore more acute than chronic heart failure.

Ageing affects diastolic function more than systolic [28]. Ageing and hypertension are characterized by increased deposition of interstitial and perivascular collagen in the myocardium resulting in fibrosis [16,17]. Both conditions also cause LVH [16,17]. Ventricular fibrosis (which occurs as a form of structural remodelling) and LVH result in decreased compliance and increased LV filling pressure. Fibrosis also causes reduced coronary reserve resulting in myocardial ischaemia and reparative fibrosis that in turn leads to progression of diastolic dysfunction towards overt heart failure [29]. Initially, the atrial contribution to late diastolic filling compensates for the decrease in early diastolic filling, maintaining stroke volume at the expense of increased end diastolic pressure. With time, this leads to left atrial enlargement and atrial fibrillation (AF), which is a precipitating factor for the development of acute heart failure [30].

Thus hypertension and old age, when they exist together, make an individual prone to developing DHF. Isolated systolic hypertension is a well-known association of old age. Diabetes mellitus and coronary artery disease often coexist in the elderly hypertensive and are also causes of diastolic dysfunction [30,31]. Pulmonary oedema occurring in DHF may be the result of complex interaction of conditions that synergistically exacerbate diastolic dysfunction. The fact that preclinical diastolic dysfunction is common would make this interaction more likely.

Imagine a patient with acute DHF. A common scenario is an elderly lady with hypertension and diabetes who is admitted with acute coronary syndrome that causes minor myocardial damage. Soon after admission she goes into atrial fibrillation and then develops acute pulmonary oedema. Echocardiography done during pulmonary oedema shows concentric LVH with preserved LV systolic function and abnormal diastolic variables. This lady already had preclinical LV diastolic impairment related to hypertension, diabetes and advanced age. Global acute ischaemia may have resulted in further stiffening of the ventricle and worsening of diastolic dysfunction, causing increased left ventricular end-diastolic pressure. A hypertensive response to ischaemia increased afterload and worsened diastolic function. Finally, tachycardia related to atrial fibrillation reduced LV filling time and precipitated pulmonary oedema by further increasing LVEDP. Loss of atrial contribution to ventricular filling may have also caused symptoms. Treatment of pulmonary oedema with intravenous nitrates also treats the acute ischaemia, responsible for the elevated LVEDP and rate control of AF increases the LV filling time resulting in rapid resolution of the pulmonary oedema. Outside acute episodes, such patients are unlikely to have persistent symptoms, and are unlikely to present with the chronic heart failure syndrome in an outpatients setting.

	5. Conclusions

Top Abstract 1. Introduction 2. Is it really... 3. Is it heart... 4. Diastolic heart failure... 5. Conclusions References

 
It is likely that heart failure with preserved systolic function includes a pathophysiologically heterogeneous group of conditions and some misdiagnosis. Each problem may require a different therapeutic approach. How many falls into which category remains unknown. Large randomised controlled trials with unfocussed entry criteria may not be the most effective approach to finding useful treatments.

	References

Top Abstract 1. Introduction 2. Is it really... 3. Is it heart... 4. Diastolic heart failure... 5. Conclusions References

 

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