How does blood pressure change in hypertensive patients with atrial fibrillation after successful electrical cardioversion?

Abstract

If the restoration of sinus rhythm (SR) by electrical cardioversion (ECV) in patients with atrial fibrillation (AF) may have a role in inducing blood pressure (BP) changes over time, it remains a largely unaddressed topic. This appears surprising in relation to the fact that AF and systemic hypertension constitute two closely related clinical entities. Indeed, AF is the most common sustained cardiac arrhythmia and, in turn, hypertension is the most common comorbid condition associated with AF.1 Moreover, the risk of stroke, heart failure, and cardiovascular mortality in patients with both AF and hypertension is markedly greater when compared with either condition alone. AF is a rapidly growing public health and socio-economic burden worldwide. It has been calculated that the total number of individuals with clinically diagnosed AF could increase from around 30-35 million (estimated data in 2010) to over 60-70 million over the next 30 years, as a result of demographic changes related to the progressive increase in life expectancy and the rising prevalence of risk factors for AF such as hypertension, diabetes mellitus, obesity, and chronic kidney disease.2 The clinical relevance of hypertension as a primary risk factor for AF in the general population has been clearly demonstrated by the Framingham Study researchers 25 years ago.3 In an analysis of 4731 individuals free of AF at entry, hypertension, defined as taking BP lowering drugs or a systolic BP of 160 mm Hg or greater, was associated with a 50% higher risk of incident AF in men and a 40% higher risk in women. Recent findings from the Clinical Practice Research Datalink (CPRD), a primary care database representative of the UK population in terms of age, sex, and ethnicity, examining 4.3 million individuals and 128 468 incident AF events, showed that systolic and diastolic BP were positively related to risk of AF.4 A 20-mm Hg higher usual systolic BP was associated with a higher risk of AF [hazard ratio (HR) 1.21]. In the Women's Health Study, including 34 221 participants free of prevalent cardiovascular disease at baseline, clinic BP was strongly associated with incident AF, and systolic BP was a better predictor than diastolic BP. Of note, systolic BP levels within the non-hypertensive range were independently associated with incident AF even after taking into account BP changes over time.5 It is worth noting that information on the contribution of ambulatory BP monitoring (ABPM) components to the risk of developing AF is scanty. Data collected from 2776 subjects randomly recruited from the general population in five European countries showed that each standard deviation (SD) increase in baseline 24-hour, daytime and nighttime systolic BP was associated with a 27%, 22%, and 20% significant increase in the risk for incident AF, respectively.6 In the Oulu Project Elucidating Risk of Atherosclerosis (OPERA), the value of ABPM components in predicting the long-term risk of AF was assessed in 903 subjects with or without hypertension aged 40 to 59 years.7 Among the baseline ABPM components, the nighttime mean systolic BP turned out to be an independent predictor of the occurrence of AF (HR = 1.07 per every 5 mm Hg increase). A mounting body of evidence suggests that reductions in BP can lower the risk of developing new AF. There is debate about the hypothesis that more intensive treatment aimed at greater reduction of BP can have an additional positive effect in preventing new-onset AF. The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study examined whether lower achieved systolic BP (≤130 mm Hg) was associated with a lower incidence of AF compared with standard systolic BP control (131-141 mm Hg) and less-adequate control (systolic BP ≥142 mm Hg) in 8831 hypertensive patients with left ventricular hypertrophy.8 Compared to patients with in-treatment SBP ≥142 mm Hg, those with in-treatment SBP ≤130 mm Hg had a 40% lower risk of incident AF and those with in-treatment SBP of 131 to 141 mm Hg with a 24% lower risk, respectively. Finally, a number of studies indicated that a sub-optimal treatment of elevated BP in patients with AF is associated with a markedly higher risk of stroke and cardiac events. The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial reported that elevated BP measurements at any point during the trial were associated with a subsequent 50% increase in risk of stroke or systemic embolism (HR, 1.53).9 In this complex scenario, the study of Olbers et al offers a new piece of evidence on BP changes following the SR restoration obtained with ECV.10 In their retrospective analysis, including 487 patients with AF, who underwent elective ECV, a recovery of an SR was observed in 59.3% (n = 289) of the cases after one week. In the group of patients converted to SR, there was a significant increase in systolic BP (from 129 ± 17 mm Hg to 137 ± 18 mm Hg, P < 0.001), with a decrease in diastolic BP (from 82 ± 9 mm Hg to 79 ± 10 mm Hg, P < 0.01). In contrast, no significant changes in both systolic and diastolic were found in the group of 198 patients with persistent or relapsing AF. Before commenting the strengths and limitations of the paper by Olbers et al,10 it may be useful to briefly summarize the findings provided by previous studies on this topic. In a paper aimed to assess changes in exercise capacity, echocardiographic parameters, and plasma atrial natriuretic peptide concentrations in 42 patients with persistent AF, before and 30 days after ECV there were no statistical differences in office BP between the two groups with and without successful procedure.11 No statistically significant change in daily BP, as assessed by ABPM performed before and after ECV, was found by Olsen et al12 in a group of 42 AF patients. In particular, they failed to demonstrate differences between the patients who achieved SR and those who maintained AF. In a further small ABP-based study including 18 hypertensive patients with successful ECV, the restoration of SR resulted in a sustained decrease in diastolic and mean BP one day after ECV and this trend persisted after 1-month of follow-up.13 A further investigation focused on the impact of ECV on sublingual microcirculation by side-stream darkfield imaging in 14 patients converted from AF to SR and showed a significant decrease in systolic and diastolic BP after the procedure.14 A retrospective study by Ramirez et al,15 encompassing a total of 159 hypertensive patients with AF, suggested that successful catheter ablation was associated with a reduction in BP, whereas an opposite trend was observed after 1 year of follow-up in patients with failed ablation. More recently, Maselli et al demonstrated that office systolic BP increased significantly (+5 mm Hg) in 63 patients after thirty days from the recovery of SR by ECV, while, on the contrary diastolic BP showed an opposite tendency (−5 mm Hg).16 A subsequent study by the same group, in which 54 hypertensive patients underwent ABPM the day before and one month after cardioversion, documented that patients maintaining a SR at follow-up (n = 34) had significantly higher 24-hour, nighttime and daytime systolic BP, and significantly lower 24-hour, daytime, and nighttime diastolic BP.17 Whereas no significant BP changes were observed in patients with persistent or recurrent AF at follow-up (n = 20). Overall, these findings do not allow conclusions to be drawn about the effects of successful ECV on BP. This is clearly related to the significant differences between the various studies in terms of numerosity, clinical features of patients, follow-up duration, and methods of BP measurement. Many pathophysiological mechanisms can be invoked to explain the reduction of BP associated with restoration of SR. AF is associated with an increase in sympathetic nerve activity resulting in vascular and renal changes that promote hypertension. Furthermore, numerous studies have shown that AF is associated with activation of the renin-angiotensin-aldosterone system (RAAS), endothelial dysfunction and depressed nitric oxide bioavailability. Indeed, it has been reported that a successful ECV in patients with persistent AF is accompanied by a marked reduction in aldosterone levels.18 On the other hand, studies that have shown an increase in systolic pressure have called for several hemodynamic changes following ECV (ie, an increase of the ejection fraction, the duration of the diastolic phase, and the cardiac output) in support of their results. The above-mentioned changes may be particularly relevant in AF patients with ventricular dysfunction and marked irregularity of the ventricular response. The study by Olbers et al, showing a clear-cut increase of the systolic BP values and consequently of the prevalence uncontrolled hypertensive (+40%) after restoration of SR, has the merit of being based on the largest series published so far. A very critical point in this type of study represented by variations in therapy during follow-up was appropriately addressed by the authors analyzing the data of the subgroup in which therapy after ECV was not changed (ie, 371 out 487 patients). Even eliminating the confounding effect of therapeutic modifications, the increase in systolic BP remained clinically relevant and similar to that observed in the total sample. An additional interesting observation is that not only hypertensive patients but also those without a pre-existing diagnosis of hypertension exhibited significant BP increments after ECV. Although the information provided by this study is based on a retrospective design, a short duration of follow-up (reduction of sympathetic and RAAS activation may take longer than a week) and supine BP measurement has the great value to stress the issue of BP control in AF hypertensive patients submitted to ECV. In conclusion, the findings from the Olbers study suggest that restoration of SR in individuals with FA may require a re-evaluation of antihypertensive therapy in order to reduce the high cardiovascular risk associated with insufficient BP control in this setting;19 but, at the same time, they indicate that further investigations are needed to clarify the controversial aspects of this important topic. The authors report no conflicts of interest.