Vasovagal the role of 24 h ambulatory blood pressure monitoring

Authors: Michele Brignole, Giulia Rivasi

Abstract

The haemodynamic mechanisms underlying vasovagal (reflex) syncope include hypotension and extrinsic asystole/bradycardia, corresponding to two distinct haemodynamic phenotypes of syncope, that is, the hypotensive and the bradycardic phenotypes. The hypotensive phenotype is the most prevalent, being observed in the 83% of patients. Twenty-four hours ambulatory blood pressure monitoring (ABPM) demonstrated high effectiveness in identifying the hypotensive phenotype in patients with suspected reflex syncope. The diagnosis of a hypotensive mechanism of syncope is supported by ABPM when one or more of the following criteria are . Constitutional 24-h systolic blood pressure (SBP) < 105 mmHg in men and <98 in women. Drug-related 24-h SBP <120 mmHg. Hypotensive ≥1 daytime SBP <90 mmHg or ≥2 daytime SBP <100 mmHg. Postprandial symptomatic SBP fall >20 mmHg or absolute value <90 mmHg within 75 min of meals. ABPM also plays a key role in guiding therapy. In hypertensive patients with hypotensive syncope, deprescribing antihypertensive medications is indicated with the goal of increasing 24-h average SBP to ≥ 134 mmHg and/or by at least ≥12 mmHg, without exceeding 140 mmHg (or <160 mmHg in frail older patients). In patients with drug-unrelated hypotension, lower-body elastic garments, fludrocortisone, or midodrine—prescribed singularly or in combination—may be considered and targeted to achieve a 24-h average SBP ≥116 mmHg and/or an increase of at least ≥9 mmHg.

Background

In recent years, 24-h ambulatory blood pressure monitoring (ABPM) has assumed a central role in the diagnostic work-up of vasovagal (reflex) syncope, driven by advances in understanding of its pathophysiology.^1,2^ A comparison of six community-based cohort studies with a large dataset of reflex syncope patients (64 968 and 6516 observations, respectively) has revealed that individuals with reflex syncope have a different haemodynamic profile compared with the general population, characterized by lower systolic blood pressure (SBP), higher diastolic blood pressure (DBP), and heart rate (HR).^1^ These haemodynamic features suggest that reflex syncope patients may have reduced venous return and lower stroke volume, which in turn induce compensatory increases in HR and vascular resistance. This fragile cardiovascular homeostasis denotes a latent predisposition to reflex syncope—termed hypotensive susceptibility—which is counterbalanced by chronic activation of compensatory mechanisms aimed at maintaining adequate organ perfusion. In individuals with hypotensive susceptibility, syncope may occur when triggering conditions (e.g. prolonged standing) exceed the capacity of these compensatory mechanisms, ultimately leading to a drop in BP, cerebral hypoperfusion, and syncope. Further evidence comes from a study by Fedorowski et al.^2^ which demonstrated that tilt-positive patients have lower SBP, DBP, and HR than tilt-negative patients with similar presentations, independently of age and gender. These findings suggest a reduced capacity to compensate for low SBP, expressed by lower DBP and HR, in tilt-positive compared to tilt-negative patients.

The above findings support the interpretation of syncope primarily as a cardiovascular haemodynamic disorder rather than a neurological phenomenon, and revealed a central role of hypotension as a triggering event in reflex syncope.

The diagnostic role of ambulatory blood pressure monitoring in reflex syncope

The haemodynamic mechanisms underlying vasovagal (reflex) syncope include hypotension and extrinsic asystole/bradycardia, that is, vagally mediated HR reduction. These mechanisms correspond to two distinct haemodynamic phenotypes of syncope, that is, the hypotensive and the bradycardic phenotypes.^3^ In a recent study of patients with suspected reflex syncope who underwent a two-step diagnostic strategy involving 24-h ABPM and tilt-based short cardiovascular autonomic function assessment,^4^ the hypotensive phenotype emerged as the most prevalent, being observed in 83% of patients. ABPM demonstrated high effectiveness in identifying the hypotensive phenotype, which was documented in 60% of these patients. Notably, ABPM cannot assess the cardioinhibitory component of the reflex, but it can reveal hypotensive episodes capable of triggering a vagal response, including cardioinhibition and asystole.

Despite its relevance, hypotension often receives limited attention in hypertension trials due to the frequent exclusion of patients with orthostatic hypotension or low standing blood pressure. Consequently, hypotension detected by ABPM is also frequently underreported. Nevertheless, identifying hypotension through ABPM is of critical importance, as it enables the recognition of patients with syncope who may benefit from therapeutic interventions aimed at increasing BP.

Diagnostic criteria

The detection of hypotension on ABPM supports the diagnosis of a hypotensive phenotype of reflex syncope. Hypotension may be persistent (i.e. manifesting as low average BP values over the 24 h period) or intermittent (i.e. manifesting as BP drops).

Recent studies have shown that patients with reflex syncope exhibit a higher frequency of daytime hypotensive episodes on 24-h ABPM compared with non-syncopal controls. Specifically, the presence of ≥1 daytime SBP measure <90 mmHg or ≥2 daytime SBP measures <100 mmHg has been strongly associated with a diagnosis of reflex syncope, thereby indicating a hypotensive syncope phenotype (Figure 1).^5,6^

Another form of intermittent hypotension that can be diagnosed by ABPM is postprandial hypotension, that is, a BP reduction following food intake. Analogous to orthostatic hypotension, postprandial hypotension is commonly defined as a SBP decrease >20 mmHg (or an absolute SBP <90 mmHg) occurring within 75 min of eating meals, compared with the average BP over the previous 2 h.^3,7,8^ Accurate diagnosis of post-prandial hypotension on ABPM requires serial BP measurements (e.g. ≥4 readings/h during the 2 h before and after each meal) in combination with a detailed daily diary documenting meal timing and rest periods.

In addition to intermittent hypotension, the hypotensive phenotype of reflex syncope may also manifest as persistently low BP values, which may either be spontaneous (constitutional) or drug related. Constitutional hypotension is a chronic condition characterized by inappropriately low BP (i.e. office SBP <100 mm Hg in women and <110 mm Hg in men) in the absence of underlying disease and antihypertensive treatment.^9^ On ABPM, it can be defined as 24 h SBP below the 5th percentile, that is, < 105 mmHg in men and <98 mmHg in women (Figure 2).^3,10^

Drug-related hypotension is defined as the presence of persistently low BP values in hypertensive patients receiving antihypertensive therapy, such that the risk of adverse hypotensive events outweighs the cardiovascular benefits of BP reduction. Accordingly, the threshold for drug-related hypotension corresponds to the BP level associated with the lowest combined risk of cardiovascular outcomes and hypotension-related adverse events, which is generally located around a SBP of approximately 120 mmHg. However, this threshold is not uniform across the general population; rather, it varies depending on age and frailty. In older or frail adults—who are at higher risk of hypotensive events and syncope—higher SBP values (i.e. <140–160 mmHg) may already be considered too low.

Finally, some findings on ABPM may suggest the presence of cardiovascular dysautonomia, a condition characterized by marked BP instability including supine hypertension, as well as orthostatic and post-prandial hypotension. Typical ABPM findings associated with cardiovascular dysautonomia include high BP variability, supine hypertension and/or reverse dipping, daytime hypotension (particularly post-prandial hypotension), and reduced HR variability.^11^

Treatment

ABPM also plays an important role in guiding therapy. Normalization or prevention of hypotension detected on ABPM through appropriate treatment is associated with clinical benefit, namely the reduction or complete prevention of syncope recurrences (Table 1).

In two randomized trials,^12,13^ the reduction/withdrawal of antihypertensive therapy in patients with hypotensive syncope or orthostatic hypotension resulted in a significant decrease in syncopal recurrences and hypotensive episodes. In an exploratory analysis of the SynABPM2 study,^4^ achieving an absolute 24-h SBP ≥134 mmHg and/or an increase of ≥12 mmHg was associated with a complete abolition of daily SBP drops <100 mmHg on ABPM (Figure 2).

Similarly, in patients with an ABPM diagnosis of constitutional hypotension, administration of BP-increasing drugs (fludrocortisone, midodrine, or their association) was associated with a reduction in syncopal recurrences and hypotensive episodes on ABPM.^14-16^

Conclusions

The hypotensive phenotype is the most frequent form of vasovagal (reflex) syncope and is characterized by a predominant hypotensive mechanism. ABPM allows identification of several manifestations of hypotension associated with the hypotensive phenotype and should be performed in all patients with likely vasovagal (reflex) syncope who present with severe or recurrent episodes, in whom mechanism-specific therapy is indicated (Table 1 and Figure 2).^3^ The identification of hypotension on ABPM has important therapeutic implications, enabling clinicians to recognize patients who may benefit from interventions aimed at increasing BP.