European Journal of Heart Failure

European Journal of Heart Failure 2005 7(2):149-156; doi:10.1016/j.ejheart.2004.05.010

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© 2005 European Society of Cardiology

Ambulatory blood pressure monitoring in heart failure: a systematic review

Deepak Goyal^a, Robert J. Macfadyen^a, Robert D. Watson^b and Gregory Y.H. Lip^*,a

^a University Department of Medicine, Sandwell and West Birmingham NHS Trust, City Hospital Dudley Road, Birmingham B18 7QH, UK
^b Department of Cardiology, Sandwell and West Birmingham NHS Trust, City Hospital Birmingham B18 7QH, UK

^* Corresponding author. Tel.: +44-121-5075080; fax: +44-121-5544083. E-mail address: g.y.h.lip{at}bham.ac.uk

	Abstract

Top Abstract 1. Introduction 2. Literature search strategy 3. Ambulatory blood pressure:... 4. Circadian variability of... 5. Studies of ABPM... 6. ABPM as a... 7. Potential uses of... 8. Conclusion References

 
Ambulatory blood pressure monitoring has established its use in the definition of white coat hypertension and monitoring of treatment of essential hypertension. Any role for ambulatory blood pressure monitoring in heart failure is not well defined. However, from the limited studies available, ambulatory blood pressure monitoring may be used to optimise heart failure therapy, and as a prognosis marker in this patient group.

Most studies that have examined the circadian pressure profile have found blunting of decline of blood pressure during sleep in patients with heart failure. In advanced heart failure, this may be due to hypoperfusion of vital organs partly due to pump failure and partly due to multiple drug therapy associated with the treatment of heart failure. Ambulatory blood pressure monitoring may also clarify hypoperfusion effects on vital organs in individual patients and improve the risk/benefit ratio of treatments in advanced heart failure. Prospective controlled studies on the impact of treatments on circadian blood pressure profile in congestive heart failure patients are needed.

Key Words: Ambulatory blood pressure • Congestive heart failure • Angiotensin-converting enzyme inhibitors • Circadian variation • Non-dippers

Received March 24, 2004; Accepted May 27, 2004

	1. Introduction

Top Abstract 1. Introduction 2. Literature search strategy 3. Ambulatory blood pressure:... 4. Circadian variability of... 5. Studies of ABPM... 6. ABPM as a... 7. Potential uses of... 8. Conclusion References

 
The prevalence of systolic heart failure is rising progressively with an ageing population and the improved salvage rates of acute coronary disease. Heart failure symptoms are increasingly common and debilitating. Symptoms due to both systolic or diastolic dysfunction of the heart are associated with significant morbidity, recurrent hospitalisations and mortality. In particular, the recurrent hospital admission pattern and its associated expenses makes this disease cluster a major public health problem [1,2].

While heart failure management is predominantly a cardiac subspeciality, most patients are managed for the majority of the time in the community. The large European survey of heart failure diagnosis, assessment and treatment (IMPROVEMENT) showed very variable standards of practice across the countries audited and variable levels of community care [3,4]. Given the prevalence of heart failure symptoms and diagnoses in the old age, it is likely that geriatricians, general hospital physicians and community doctors are involved more often than cardiologists. Multiple co-morbidity is common to the majority of heart failure patients, most of whom are in the elderly (>70 years) or very elderly (>80 years) age range.

1.1. Blood pressure in heart failure patients
One of the most common co-morbidities and precursors of a heart failure diagnosis is arterial hypertension. Hypertension often antedates heart failure in the general population and plays a central role in the evolution of the syndrome [5–7]. From a population association stand point, hypertension is the principal risk factor for the development of left ventricular hypertrophy (LVH) [8] and for myocardial infarction (MI), which is a common precursor to LV systolic dysfunction (either by inter current infarction or remodelling to LV dilatation). Hypertensive LVH leads more directly to ventricular diastolic dysfunction, which in turn may progress to the emergence of heart failure symptoms [9,10]. There is thus a close association between hypertension and heart failure despite these being radically different conditions (see Fig. 1).

View larger version (18K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 1 From hypertension to heart failure.

 
Before the onset of heart failure symptoms, high arterial pressure is common. After the onset of symptoms and evolution of systolic pump failure, low or fluctuating blood pressure is also common. In addition, most evidence-based therapies of systolic heart failure also tend to lower arterial blood pressure. While a simple vasodilator concept of cardiac off loading as a treatment for systolic heart failure was previously accepted, this has now been modified and pure vasodilator therapy is not generally regarded as effective. Low arterial pressure created either by incipient shock, vasodilator treatment or dehydration (iatrogenic or disease-related) will all compromise critical organ perfusion, primarily the brain (and can give rise to vague light headedness; pre syncope; or true syncope) and the kidneys (with potentially reversible pre renal failure even with agents not blocking any aspect of the renin–angiotensin–aldosterone system).

Balancing the effects of therapy against critical haemodynamic perfusion thresholds (with variable limits for each major organ) is therefore essential. In keeping with the importance of this concept, low arterial blood pressure due to cardiogenic failure is commonly associated with a very poor outcome [11]. Moreover, patients with advanced congestive heart failure (NYHA IV) who have preserved systolic blood pressure are more likely to survive [12]. Thus, in heart failure patients, particularly in the elderly, a careful balance needs to be made between therapies that might lower blood pressure (and directly or indirectly improving symptoms and prognosis of heart failure) whilst preserving arterial blood pressure to avoid hypoperfusion effects.

Ambulatory blood pressure monitoring while used routinely for two decades in hypertension care has rarely been applied in CHF patients. This simple technology can help evaluate orthostatic symptoms, potential autonomic imbalance and the titration of multiple agents with haemodynamic effects in patients with systolic CHF. In this structured review, we place current knowledge of ambulatory blood pressure in CHF into its clinical context and consider whether or not it may have broader applications in routine care of CHF.

	2. Literature search strategy

Top Abstract 1. Introduction 2. Literature search strategy 3. Ambulatory blood pressure:... 4. Circadian variability of... 5. Studies of ABPM... 6. ABPM as a... 7. Potential uses of... 8. Conclusion References

 
We performed a comprehensive literature search using electronic databases (MEDLINE, EMBASE, DARE, the Cochrane database of trials), using the search terms ‘ambulatory blood pressure’ in combination with either ‘heart failure’, ‘monitoring’, ‘hypertension’ and ‘diastolic dysfunction’, etc., to cover the range of subheadings addressed in this review. The years studied were from 1982 to 2003 (September). In addition, the reference lists from identified key original reports were scrutinized and abstracts from national and international cardiovascular meetings (ISI Web of Knowledge) were studied to identify further studies, published only in abstract or cited as unpublished work. Papers focusing on manual clinic blood pressure readings or those on acute or decompensated heart failure patients' were not considered in this structured review.

	3. Ambulatory blood pressure: methodology and relationships to morbidity and mortality

Top Abstract 1. Introduction 2. Literature search strategy 3. Ambulatory blood pressure:... 4. Circadian variability of... 5. Studies of ABPM... 6. ABPM as a... 7. Potential uses of... 8. Conclusion References

 
Non-invasive, intermittent blood pressure monitoring was first developed more than 30 years ago from earlier studies of continuous intra-arterial pressure monitoring. The principle of measurements has ranged from auscultated Kortotkoff sounds to more modern oscillometric devices. Modern hardware has allowed smaller pump function, increased technical reliability and more robust construction, flexible programmability, and concomitant electrocardiography monitoring and digital data storage. In this present era, the devices are more compact, fully automated and electronically sophisticated making them very easy to use.

Ambulatory blood pressure devices have two main methods of blood pressure detection: auscultatory and oscillometric detection of pressure cuff deflation pulse waveforms. These are generally studies in the non-dominant arm of the brachial waveform. The auscultatory method uses a microphone to detect Kortokoff sounds whereas the oscillometric method detects the initial (systolic blood pressure) pulse by counter pressure in the closed loop device and maximal (mean arterial pressure) oscillations of the brachial artery, calculating diastolic blood pressure either with a validated algorithm or by the loss of pulsatile pressure change. Both methods are less reliable in presence of an irregular pulse (such as in atrial fibrillation) through increased variance, although the method has been used successfully to outpatients with chronic atrial fibrillation and hypertension [13]. The frequency of recordings, the impact of ambulatory activity, mental and physical stress, and motion artefact and sleep cycle disturbance have all received extensive consideration in the hypertension literature. In addition, none of these issues invalidate or devalue the impact of repeated measures of blood pressure in a non-clinic environment.

Ambulatory blood pressure monitoring is most notably associated with the definition of white coat hypertension. This is simply the almost universal overestimation of blood pressure by readings taken in the office or clinic setting. In hypertension, several cross-sectional studies have shown that prevailing ambulatory blood pressure monitoring data better defines target organ damage, such as left ventricular hypertrophy [14–17], microalbuminuria [18], retinal hypertensive changes and cerebrovascular disease [19] than office-based readings even ones taken with a strict protocol of observation. Recently, Clement et al. [20] reported the results of the Office versus Ambulatory Pressure Study, demonstrating that cardiovascular outcomes in treated patients with hypertension are better predicted by ambulatory blood pressure than by the office blood pressure. Several other prospective ambulatory blood pressure studies have also shown that ambulatory blood pressure is a far better predictor of cardiovascular events than the standard office or clinic blood pressure in patients with hypertension [14,21–27].

Ambulatory blood pressure monitoring has also been useful to define those hypertensive patients who lose their normal nocturnal dip in blood pressure during sleep. These patients are referred to as non-dippers. These patients may have higher prevalence of target organ damage. The prevalence of this non-dipping profile has been reported to be between 17% and 40% in patients with hypertension [28,29].

While all these aspects are routine knowledge in patients with hypertension (many having been established for decades), their relevance to patients who progress from hypertension to either diastolic or systolic heart failure is barely addressed.

	4. Circadian variability of blood pressure in heart failure

Top Abstract 1. Introduction 2. Literature search strategy 3. Ambulatory blood pressure:... 4. Circadian variability of... 5. Studies of ABPM... 6. ABPM as a... 7. Potential uses of... 8. Conclusion References

 
There are limited data on the application of ambulatory blood pressure monitoring in chronic systolic heart failure. Indeed, there are also little data on whether there was the same variation between ABPM and office blood pressure recordings in heart failure that is commonly seen in hypertension.

Unaccounted treatment effects of various heart failure medications confound blood pressure observations in these groups. The normal circadian variation in blood pressure and heart rate is altered by systolic heart failure. As the severity of ventricular impairment progresses, there is a corresponding reduction in the variability of both blood pressure and heart rate [30,31]. Conversely, effective heart failure treatment with the ACE inhibitors (regardless of pressure lowering) seems to increase the circadian variation of blood pressure [32]. Indeed, understanding the circadian variation in blood pressure during heart failure management with vasodilator drugs may have both pathophysiological and therapeutic implications for the effectiveness of therapy in individual cases.

Normal circadian variation in blood pressure and heart rate does alter following the development of heart failure. The normal circadian variation in blood pressure and heart rate shows bimodality, the lesser mode being predominantly due to sleep [33]. Various mechanisms control circadian variation in normal subjects, including physical activity, posture, baroreflexes, sympathetic and parasympathetic activity. There is also a circadian variation in plasma levels of vasoactive neurohormones such as norepinephrine, epinephrine [34], atrial natriuretic peptide and plasma renin activity in normal subjects [35]. Alterations in the diurnal patterns of these substances in heart failure are well established, and these may be behind the altered pressure profiles attributable to the disease per se. As indicated above, on top of these are the changes attributable to pharmacological and non-pharmacological treatment of heart failure.

Congestive heart failure is associated with alterations in sympathetic and parasympathetic nervous system, renin–angiotensin system and vasopressin and ANP secretion [36]. Indeed, patients with severe congestive heart failure have increased sympathetic nervous activity and impaired baroreceptor function, which will directly influence diurnal blood pressure profile. Thus, the circadian variability of systolic blood pressure represents multiple factors, which characterise an integrated response of the cardiovascular system.

	5. Studies of ABPM in heart failure

Top Abstract 1. Introduction 2. Literature search strategy 3. Ambulatory blood pressure:... 4. Circadian variability of... 5. Studies of ABPM... 6. ABPM as a... 7. Potential uses of... 8. Conclusion References

 
5.1. Patterns of response
The range of published studies using ABPM in chronic systolic heart failure are summarised in Table 1. Caruana et al. [30] defined the continuous intra-arterial ambulatory blood pressure profile of 20 patients with chronic congestive heart failure due to coronary artery disease and compared this with previously published data on intra-arterial blood pressure of 22 healthy volunteers. They suggested that the long- and short-term circadian variability of systolic blood pressure and heart rate were significantly less in the heart failure group as compared with healthy volunteers. This finding of a reduction in the circadian variability of blood pressure in systolic heart failure patients was supported by several subsequent controlled studies [30–32,37,38] although again there were some exceptions to the observation [39].

View this table: [in this window] [in a new window]   Table 1 Ambulatory blood pressure monitoring in heart failure

 
5.2. Impact of drug therapy: the example of ACE inhibition
Few individual therapies effective in the management of systolic heart failure have had comprehensive assessment of their diurnal profile of haemodynamic effects or other efficacy for that matter. ACE inhibition is one of the rare examples where ABPM has been assessed in small patient trials. The reasons for these studies have related to concerns over the general haemodynamic or more specifically renal perfusion effects of ACE inhibitor therapy possibly acting to the detriment of the patient with heart failure.

In 1996, Giles et al. [32] suggested from a study of ABPM in 30 patients with heart failure that there was an inverse relationship between the absolute amplitude of systolic blood pressure, and rate–pressure product and plasma norepinephrine concentrations. They showed that the degree of variability of circadian blood pressure was directly related to the cardiovascular indices of the severity of heart failure (patients with higher left ventricular ejection fraction had a greater variability in circadian pressure profile) and indirectly related to the neurohumoral activity. In the same report, they demonstrated that treatment with ACE inhibitors restored some degree of autonomic control, as reflected by a more normal variability of circadian patterns of blood pressure [32].

In a subsequent substudy of multicentre trial of dose response to the ACE inhibitor lisinopril (The ATLAS trial; 5 versus 35 mg given once daily), Giles et al. [40] showed a greater diurnal variability of systolic blood pressure after treatment with high-dose lisinopril as compared with low-dose lisinopril. Whether this related to increased variability within individual patients (restoring a more normal pattern) or simply represents a dose effect on the treated mean blood pressure reduction responses is less clear. Clearly, low-dose therapy would have a less significant mean effect but potentially might have a greater intra individual effect.

	6. ABPM as a prognostic marker in heart failure

Top Abstract 1. Introduction 2. Literature search strategy 3. Ambulatory blood pressure:... 4. Circadian variability of... 5. Studies of ABPM... 6. ABPM as a... 7. Potential uses of... 8. Conclusion References

 
The link between blood pressure and outcome in heart failure can be made at a variety of levels. In a subset of 181 CHF patients from the Rotterdam Heart Study, Mosterd et al. [11] found that those community CHF patients with a higher blood pressure had a better outcome. Similarly, Canesin et al. [12] studied 24-h ambulatory blood pressure in 38 patients with advanced NYHA IV congestive heart failure and also assessed their left ventricular ejection fraction and end diastolic diameter. These patients were then followed up for a minimum period of at least 6 months where 12 deaths occurred in this period. The mean 24-h, waking, and sleeping systolic pressures of the living patients were higher than those of the deceased patients and were significant for predicting survival. Patients with a nocturnal diastolic blood pressure dip of less than 6 mm Hg had longer survival. Conversely, patients with mean nocturnal systolic blood pressure of <105 mm Hg were 7.6 times more likely to die than those with SBP105 mm Hg [12]. In this study, left ventricular ejection fraction (35.2±7.3%) and diastolic diameter (72.2±7.8 mm) were not correlated with the survival.

6.1. ABPM and diastolic dysfunction
The definition of diastolic heart failure is gradually improving with respect to clinical presentation (heart failure symptoms with normal long axis and short axis systolic contractility), exclusion of relevant alternative diagnoses (ischaemia, valvular disease, occult arrhythmia, pericardial disease, restrictive cardiomyopathy, and lung disease and simple obesity), the interpretation and echocardiographic definition of diastolic filling abnormalities and clinical morbidity and mortality. However, it still remains a controversial entity due to the above confusing features and equally it is clearly a less clamant state than that of systolic heart failure but is associated with clearly elevated morbidity and mortality. Diastolic heart failure is closely associated with echocardiographic ventricular hypertrophy, left atrial dilatation, and abnormal pulmonary valve in flow and abnormal transmitral filling in hypertension. As above, systolic function is normal or "near normal".

While abnormalities of systolic and diastolic function can coexist in congestive heart failure, isolated diastolic dysfunction may account for as much as 30–40% of patients presenting with a presumed diagnosis of left ventricular failure [41–44]. Increased afterload is a major contributor to the development of diastolic dysfunction, and left ventricular filling impairment has been recognised as an early finding in arterial hypertension, even when systolic function is intact [9,45]. Various indices, primarily involving Doppler echocardiography and radionuclide ventriculography, have been developed to estimate diastolic dysfunction. In normal subjects, the early diastolic mitral velocity (E) exceeds that following atrial systole (A). However, with the advent of diastolic dysfunction, the mitral flow velocity in early diastole (E) decreases and the late velocity (A) increases. This reversal of E/A ratio is the simplest but sadly also the least specific of the parameters commonly used to suggest diastolic filling abnormalities.

The direct relationship between clinic blood pressure readings on diastolic function has not been clearly defined. White et al. [46] has previously described an inverse relation of ambulatory blood pressure with diastolic dysfunction. It has also been observed that blood pressure recorded over a 24-h period has a strong inverse relationship to early left ventricular filling parameters, suggesting that a pressure overload detected by ambulatory readings may be a major determinant of left ventricular diastolic dysfunction [47]. Furthermore, Galderisi et al. [48] studied ambulatory blood pressure in 125 subjects and divided these patients into two groups based on presence or absence of diastolic dysfunction, which was simply assessed by Doppler-derived ratio of peak early to atrial transmitral filling velocity (E/A ratio). They found that patients with evidence of diastolic dysfunction were older and had higher LV mass index, average 24-h BP, average nighttime BP, and lower day–night BP decrease [48]. Hence, high average nocturnal diastolic BP is a powerful marker of association to these echocardiographic indices of impaired LV filling.

	7. Potential uses of ambulatory blood pressure monitoring in heart failure

Top Abstract 1. Introduction 2. Literature search strategy 3. Ambulatory blood pressure:... 4. Circadian variability of... 5. Studies of ABPM... 6. ABPM as a... 7. Potential uses of... 8. Conclusion References

 
7.1. Optimising heart failure medication:
Low clinic blood pressure readings have been a major factor responsible for the poor uptake of hormone based therapies such as the ACE inhibitors [49,50] and angiotensin receptor antagonists [51]. Similarly, it is also likely to explain some of the under utilisation of beta-blocker therapy. While it is theoretically possible that at a certain point in the course of heart failure, blood pressure lowering can be detrimental, the practical definition of these thresholds and the key factors behind them are still left unclear. Ambulatory blood pressure may be helpful in defining these thresholds which may be nocturnal (and therefore go unrecognised) and may help patients to get optimum heart failure treatment, balancing haemodynamic effects in the community setting.

7.2. Correlation with symptoms
A great deal has been achieved in the past 20 years by a variety of drug therapies to give impressive reductions in mortality and hospital admissions in patients of systolic heart failure. Most of these medications have a significant hypotensive effect. Furthermore, the polypharmacy associated with treatment of heart failure along with advanced pump failure is undoubtedly associated with symptoms of orthostatic dizziness and worsening renal hypoperfusion notwithstanding the beneficial effects of the drugs used on the kidney is predominantly to preserve function. Hypoperfusion of vital organs can equally lead to significant morbidity and mortality. Ambulatory blood pressure recordings could also be of great use in identifying patients with such risks and assessing whether day/night blood pressure profiles are helpful in predicting adverse events such as renal dysfunction or mortality.

7.3. Assessing the heart rate–pressure ‘load’
Blood pressure load has been shown to correlate more closely with end organ damage than the 24-h mean blood pressure in patients with hypertension [46,52]. Hypertension precedes the development of major congestive heart failure in approximately 40% of patients. The heart rate–blood pressure product critically determines cardiac workload [53]. This assessment of heart rate pressure load by ambulatory blood pressure recordings may provide a useful goal for therapy in heart failure patients.

7.4. As a research tool
Ambulatory blood pressure can be used to study the time course of drug effects and the extent of drug action. This can be a therapeutic goal in some, a surrogate marker of effect in others and a safety issue in another context. This is clearly important in clinical definition of new treatments and to monitor patients receiving either approved or new medications. First dose effects of drugs can be quantified; indeed, peak and trough blood pressure effects can be more accurately judged than with casual recordings. Patients with a loss of haemodynamic effect or rebound blood pressure changes within a dosing interval can be identified. Recordings from ambulatory blood pressure can occasionally alert researchers to the presence of an active metabolite, which may have delayed onset of action or be responsible for prolonged hypotensive properties.

7.5. Improving patient compliance
Ambulatory blood pressure monitoring may provide improved follow up of patients along with better adherence of therapy. Although symptoms of heart failure are usually a better impetus to compliance, ambulatory blood pressure monitoring may help in reinforcing this in symptomatic patients. Ambulatory blood pressure monitoring can be particularly useful in asymptomatic heart failure patients with poorly controlled hypertension.

7.6. As a prognostic marker
Patients with lower mean systolic blood pressure as found by 24-h ambulatory blood pressure monitoring have a higher mortality than patients with higher mean systolic blood pressure in advanced congestive heart failure. For example, Canesin et al. [12] found that patients with NYHA class IV heart failure who had a greater mean systolic dip during sleep were associated with higher mortality. However, more prospective studies with larger number of patients are needed to corroborate these findings.

	8. Conclusion

Top Abstract 1. Introduction 2. Literature search strategy 3. Ambulatory blood pressure:... 4. Circadian variability of... 5. Studies of ABPM... 6. ABPM as a... 7. Potential uses of... 8. Conclusion References

 
Ambulatory blood pressure monitoring is an established and robust technology in hypertension management. There are few studies exploring its application in either systolic or diastolic heart failure patients either before or after multiple drug treatments now common in practice. ABP readings may reflect the integrity of the normal neurohormonal responses in congestive heart failure, central cardiac function and peripheral vasoconstriction/loading. Either symptoms or injury due to critical organ hypoperfusion induced by breaching individualised perfusion tolerances to prescribed drug therapy may be better defined by ABPM in heart failure. Further prospective outcome trials in patients with congestive heart failure need to be undertaken to better define and correlate simply levels of blood pressure at which hypoperfusion of vital organs begin. This may be productive in optimising heart failure medication to appropriate levels for the individual patient.

	References

Top Abstract 1. Introduction 2. Literature search strategy 3. Ambulatory blood pressure:... 4. Circadian variability of... 5. Studies of ABPM... 6. ABPM as a... 7. Potential uses of... 8. Conclusion References

 

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