Version May 2024
INTRODUCTION — Atrial fibrillation (AF) can lead to a fall in cardiac output that is often clinically significant. Potential consequences include a fall in blood pressure, decreased exercise capacity, and pulmonary congestion, all of which are manifestations of heart failure (HF). In addition, AF and HF often occur together, and each may predispose to the other [1].
The hemodynamic effects of AF and of cardioversion will be reviewed here. The clinical aspects and treatment of AF in patients with HF and cardiomyopathy are discussed separately. (See "The management of atrial fibrillation in patients with heart failure".)
ADVERSE HEMODYNAMICS IN AF — Many patients with atrial fibrillation (AF) develop a modest decline in left ventricular performance that typically returns to the previous baseline following reversion to sinus rhythm [2-5]. The magnitude of this effect and its reversibility were illustrated in a report of 15 patients with AF who were successfully cardioverted and maintained sinus rhythm for one month; 11 of these patients maintained sinus rhythm for three months [4]. The mean duration of AF was three months (range 5 to 254 days). The following findings were noted after cardioversion:
●The mean left ventricular ejection fraction (LVEF) increased from 47 percent at baseline to 55 percent immediately after cardioversion to 61 percent at one month; there was no further increase at three months. The improvement in LVEF occurred in all but one patient. The maximum improvement in LVEF by one month coincides with the time to full recovery of left atrial contractile function [6]. (See 'Atrial stunning' below.)
●The increase in LVEF was primarily due to enhanced diastolic filling resulting from two factors: (1) an increase in cycle length, which may involve both regularization of the heart rate and avoidance of short cycle lengths that impair ventricular contractility; and (2) the return of left atrial contractile function, as determined by peak A wave velocity, which increases the atrial contribution to ventricular filling [3,4].
The improvement in LVEF following reversion to sinus rhythm is associated with an increase in exercise capacity. (See 'Improved exercise capacity' below.)
The deleterious hemodynamic effects of chronic uncontrolled AF are more pronounced in some patients who develop a reversible tachycardia-mediated cardiomyopathy. (See 'Tachycardia-mediated cardiomyopathy' below.)
Hemodynamic deterioration also occurs in patients with underlying heart failure (HF). This issue was examined in a prospective observational study of 344 patients with HF who were initially in sinus rhythm; 28 developed AF over 19 months, 18 of whom developed chronic AF [7]. Chronic AF was associated with significant worsening of New York Heart Associated functional class (mean 2.4 to 2.9) (table 1) and a significant reduction in cardiac index (mean 2.2 to 1.8). The relatively modest changes may have reflected excellent control of the ventricular rate (78 beats/min) at the time the measurements were made. Consistent with this hypothesis is the observation that the onset of AF in 8 of the 18 patients with chronic AF was associated with overt cardiac decompensation, which presumably led to therapy to control the ventricular rate. (See "The management of atrial fibrillation in patients with heart failure".)
Contributing factors — The following factors may contribute to the adverse hemodynamic changes in AF:
●A rapid or slow heart rate; if maintained, a chronic tachycardia can lead to a rate-related cardiomyopathy (atrial or ventricular).
●The irregular rhythm.
●Loss of atrial systole (also called the atrial "kick") required for optimal ventricular filling.
●Activation of neurohumoral vasoconstrictors such as angiotensin II and norepinephrine.
Another problem demonstrated in animal models is that AF may beget AF by causing electrical remodeling of the atria, which promotes perpetuation of the arrhythmia [8,9]. This proarrhythmic process is reversible with the maintenance of sinus rhythm. The clinical relevance of this observation remains uncertain. (See "Mechanisms of atrial fibrillation", section on 'Maintenance of atrial fibrillation'.)
Rapid ventricular response — The dependence of cardiac output on heart rate is greatest in patients with left ventricular dysfunction, which is often associated with a relatively fixed stroke volume. As an example, the cardiac output is optimal over a narrow range of heart rates in patients with a myocardial infarction, falling significantly with slower or faster heart rates [10]. A rapid ventricular response is also particularly deleterious in patients with mitral stenosis in whom the reduction in the duration of diastole diminishes the time available for filling of the left ventricle across the stenotic valve [11].
The optimal heart rate for patients in permanent AF is discussed separately. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy", section on 'Evaluation and goal ventricular rate'.)
Tachycardia-mediated cardiomyopathy — Persistent, uncontrolled tachycardia can have a cardiomyopathic effect that impairs left ventricular function. This phenomenon is called a tachycardia-mediated cardiomyopathy and is reversible when the tachycardia is controlled. (See "Arrhythmia-induced cardiomyopathy".)
AF occurs in 10 to 30 percent of patients with HF but can be even higher as heart failure worsens. In most of these patients, the underlying heart disease is thought to predispose to AF. (See "The management of atrial fibrillation in patients with heart failure".) However, in some patients, restoration of sinus rhythm or control of the rapid ventricular response markedly improves or even normalizes the LVEF, indicating that the left ventricular dysfunction was primarily due to the rapid AF rather than an underlying dilated cardiomyopathy [12-14]. The benefit may be more predictable with reversion to sinus rhythm [13,15].
The following observations illustrate the potential magnitude of this effect:
●In one report, the LVEF was measured before and at a mean of 4.7 months after cardioversion in 12 patients with chronic AF and presumed idiopathic dilated cardiomyopathy [13]. There was an improvement in mean LVEF from 32 percent at baseline to 53 percent at follow-up; the LVEF returned to normal in six of the patients. This improvement persisted at one year in the 10 patients who remained in sinus rhythm, while there was a marked deterioration in left ventricular function in the two patients with recurrent AF.
●Among patients treated with rate control, the largest reported experience comes from the multicenter Ablate and Pace Trial (APT), a prospective registry of patients undergoing atrioventricular (AV) nodal ablation and pacemaker implantation for refractory AF [14]. The registry included 63 patients with left ventricular dysfunction (LVEF ≤45 percent); after atrioventricular (AV) nodal ablation, 16 (25 percent) displayed a marked improvement in LVEF to over 45 percent. The mean increase in LVEF in these patients was 27 percentage points.
Irregular heart rate — The hypothesis that an irregular rhythm itself, independent of the ventricular rate and the restoration of atrial systole, can impair hemodynamics is based in part upon short-term observations that irregular ventricular pacing or induced AF results in a decrease in cardiac output, an elevation in central venous pressure, and an increase in sympathetic nerve activity compared to regular ventricular or atrial pacing at the same mean heart rate [16,17].
Further support for the adverse effect of an irregular heart rate comes from a study of 14 patients with chronic AF and a normal ventricular response in the absence of drugs that block AV nodal conduction [18]. AV nodal ablation and insertion of a ventricular pacemaker resulted in a regular rhythm, improvements in left ventricular function, functional capacity, and the sense of well-being [18].
The adverse hemodynamic effect of an irregular rhythm may be mediated by several factors:
●Beat-to-beat variations in atrial pressure (preload). The influence of preload on left ventricular ejection (Frank-Starling mechanism) is important in AF only when afterload is relatively low [19].
●Beat-to-beat variations in myocardial contractility [20-22]. Among patients with AF, the preceding RR interval has a significant positive correlation with left ventricular ejection, as a shorter RR interval (more rapid ventricular response) reduces the LVEF [20]. This effect is independent of end-diastolic volume, indicating that it cannot be explained by the Frank-Starling mechanism. In addition, the "pre-preceding" RR interval has a negative correlation with left ventricular ejection, which has been ascribed to postextrasystolic potentiation [20,23].
●Inefficient ventricular mechanics due to abrupt changes in cycle length [16].
Atrial systole — Contraction of the left atrium injects a volume of blood under pressure into the left ventricle, leading to increments in ventricular diastolic volume, end-diastolic pressure, and stroke volume [24,25]. Loss of atrial systole can therefore diminish the stroke volume. This may be particularly important when left ventricular compliance is reduced and in mitral stenosis.
Left ventricular compliance is reduced in patients with diastolic dysfunction. In such patients, there is a relative shift of left ventricular filling to the later part of diastole with a greater dependence upon atrial contraction. Clinical examples in which AF can lead to hemodynamic deterioration in patients with diastolic dysfunction include advanced aortic stenosis, which often produces a hypertrophied, poorly compliant left ventricle, and hypertrophic cardiomyopathy.
The importance of atrial systole has been demonstrated in patients with hypertrophic cardiomyopathy, which is typically associated with an increased atrial contribution to ventricular filling (31 versus 16 percent in controls in one report) [26]. In addition, loss of the atrial contraction-induced increase in left ventricular end-diastolic volume can increase the degree of outflow tract obstruction. The net effect is that the acute onset of AF leads to worsening symptoms in the great majority of patients with hypertrophic cardiomyopathy (41 of 46 in one study) [27]. (See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation" and "Pathophysiology of heart failure with preserved ejection fraction".)
Among patients with mitral stenosis, the onset of AF can lead to hemodynamic deterioration. Two factors contribute to this adverse effect: the loss in atrial systole, which plays an important role in the generation of adequate left atrial pressure to maintain blood flow across the stenotic valve and may also reduce effective mitral valve area; and the rapid ventricular response which, due to the reduction in the duration of diastole, diminishes the time available for filling of the left ventricle [11].
The relevance of atrial systole, irregular rate, and ejection fraction was assessed in patients with systolic HF who underwent AF ablation versus AV node ablation with biventricular pacing [28]. In those who underwent AF ablation, there was a greater improvement in ejection fraction, six-minute walk test, and quality-of-life scores. It is not clear, however, whether it was due to the restoration of sinus rhythm in the AF group or presence of pacing, even though it was biventricular, in the AV node ablation group.
Neurohumoral activation — The fall in cardiac output in rapid AF may increase afterload by activating neurohumoral vasoconstrictors. In addition, AF may reversibly increase the secretion of atrial natriuretic peptide [29,30] which, via activation of other propeptides and neurohumoral mechanisms, could influence systemic hemodynamics. As an example, one study of 100 patients with and without AF found that patients with AF had higher levels of N-terminal atrial natriuretic peptide (ANP) (2.6 versus 1.7 ng/mL in those without AF); this association was independent of left atrial volume and LVEF [31]. In patients with HF and AF, the association between AF and ANP interferes with the association between left ventricular dysfunction and ANP.
While one study did not find a higher level of plasma B-type natriuretic peptide (BNP) in AF patients compared to those without [31], other studies have [32,33]. (See "Natriuretic peptide measurement in heart failure".) The relationship between baseline BNP and recurrence of AF after successful AF ablation is discussed elsewhere.
Mitral regurgitation — Preliminary data has suggested that, in a small number of patients, AF can lead to increased mitral annular dilatation and mitral regurgitation (MR). This was shown in a report of 12 patients (out of 18,695 open heart surgeries) who had AF and moderate or greater MR, with normal left ventricular size and function but symptoms of dyspnea [34]. They underwent mitral ring annuloplasty and surgical ablation, with an improvement in symptoms and MR. The presence of AF can create a cycle of worsening AF burden and increasing MR, which can be reversed with a persistent return to normal sinus rhythm [35]. Increased left atrial size in the presence of normal left ventricular function has been associated with increased mitral annular size and more severe MR in some studies [36], but not in all [37,38].
HEMODYNAMICS AFTER CONVERSION OF CHRONIC AF TO SINUS RHYTHM — As noted above, the restoration of sinus rhythm produces a rapid increase in left ventricular ejection fraction (LVEF) in most patients with atrial fibrillation (AF) [2-4]. In one report, for example, the LVEF increased from 47 to 55 percent immediately after cardioversion and to 61 percent at one month [4]. The improvement in LVEF was primarily due to enhanced diastolic filling resulting from two factors: an increase in cycle length, which may involve both regularization of the heart rate and avoidance of short cycle lengths that impair ventricular contractility; and the return of left atrial contractile function. There appears to be no change in markers of intrinsic myocardial contractility.
A similar improvement in LVEF has been demonstrated in patients treated with radiofrequency catheter ablation to maintain sinus rhythm. The magnitude of this effect was illustrated in a report of 58 patients with heart failure and AF in whom the mean LVEF improved from 35 to 56 percent and the mean New York Heart Association (NYHA) class fell from 2.3 to 1.4 (table 1) after successful ablation [39]. The greatest improvement was seen within the first three months. (See "The management of atrial fibrillation in patients with heart failure", section on 'Rhythm control'.)
Atrial stunning — Cardioversion of AF leads to an increased risk of thromboembolism, particularly if patients are not anticoagulated before, during, and after the procedure. Most emboli occur within the first week after cardioversion. In addition to dislodgement of pre-existing thrombi, some patients develop de novo thrombi that are thought to be due at least in part to persistent depression of left atrial systolic function, which can last for several weeks after successful cardioversion [6]. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation", section on 'Rationale for anticoagulation'.)
The transient atrial contractile dysfunction following cardioversion, also known as atrial "stunning," may result from a tachycardia-induced atrial cardiomyopathy, which is caused in part by impaired cellular handling of calcium [40-42]. An evaluation of stunning in a canine model revealed the following [43]:
●Stunning occurred with AF duration of only one hour. In this study and in reports of humans with AF and atrial flutter [42,44], the peak left atrial contractile velocities were lower after reversion to sinus rhythm than during the arrhythmia.
●Stunning was more profound and of longer duration in the left atrial appendage than the left atrium itself.
Reduced left atrial appendage function occurs with all forms of reversion to sinus rhythm including spontaneous cardioversion [45], external or internal direct current (DC) (electric) cardioversion [6,44,46-49], and pharmacologic cardioversion [50]. The degree of stunning appears to be greater after electrical compared to spontaneous or pharmacologic cardioversion [45], but is not related to the total amount of energy used if electrical cardioversion is performed [46,47].
Estimates of the frequency of early atrial stunning (immediately to within three days post-cardioversion) range from 20 to 55 percent [44-46]. At one week, the rate is 10 to 25 percent [45,46].
The net effect of stunning is that left atrial contractility is reduced by up to 75 percent [41] and left appendage flow velocity falls after the restoration of sinus rhythm [42,44], which can lead to local stasis, as manifested by the onset of or an increase in spontaneous echo contrast [44,48,49], and the formation of new thrombi [48,51-53]. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation", section on 'Rationale for anticoagulation'.)
The duration of the left atrial dysfunction is related in part to the duration of AF [6,50]. In a review of 60 patients who underwent successful cardioversion, full recovery of atrial mechanical function was attained within 24 hours in patients with AF for ≤2 weeks, within one week in patients with AF for two to six weeks, and within one month with more prolonged AF [6]. Recovery of atrial function is typically demonstrated by return of peak A wave velocity on Doppler echocardiography [6,50].
The time course of recovery of left atrial function could explain why the great majority of embolic events in patients who remain in sinus rhythm occur within the first 10 days after cardioversion [54,55].
De novo thrombus formation can also result in part from activation of the coagulation system and a hypercoagulable state following cardioversion [56-58]. In one study, for example, an increase in plasma concentrations of the markers of thrombin generation and activity (thrombin-antithrombin complex and fibrinopeptide A) was found soon after pharmacologic cardioversion to sinus rhythm [56]. As with atrial function, hemostatic markers return to normal by two to four weeks after cardioversion [57,58].
Pulmonary edema — An uncommon hemodynamic complication of DC cardioversion is pulmonary edema. In a review of the literature, pulmonary edema was reported in approximately 1.2 percent of cases, half of them within three hours but as late as four days after cardioversion [59]. A lower incidence of 0.4 percent was noted in a report of consecutive outpatient cardioversions at a single institution [60]. Pulmonary edema after cardioversion is more common in patients with left ventricular dysfunction or valvular heart disease [59].
Possible mechanisms for the development of pulmonary edema after cardioversion include acute left ventricular contractile dysfunction [61], which may be due in part to transient interruption of myocardial cellular respiration [62], acute left atrial dysfunction [46], and the return of right atrial before left atrial systolic function [63].
Improved exercise capacity — As mentioned above, most patients in whom AF is reverted to sinus rhythm have a significant increase in LVEF [2-4]. One beneficial effect of the improvement in hemodynamics is enhanced exercise capacity [64-66].
The magnitude of this effect was illustrated in a study of 63 consecutive patients with chronic AF who were electrically cardioverted in whom peak oxygen consumption (peak VO2) was measured before and one month after cardioversion [65]. At one month, the mean peak VO2 in the 37 patients in sinus rhythm had significantly increased from 21.4 to 23.7 mL/min per kg, while those who had reverted to AF showed no change in oxygen consumption. The patients who remained in sinus rhythm also had a significant reduction in peak heart rate and an improvement in NYHA functional class. The benefits from restoration of sinus rhythm were seen in patients with and without underlying heart disease and showed some further improvement at two-year follow-up.
Similar benefits were noted in the radiofrequency ablation study of 58 patients with heart failure (HF) cited above [39]. The mean NYHA class significantly improved from 2.3 to 1.4 after ablation in association with improvements in quality of life, exercise capacity, and exercise time. (See "The management of atrial fibrillation in patients with heart failure", section on 'Rhythm control'.)
Mitral regurgitation — A study of 53 patients examined the effect of AF ablation in those with at least moderate mitral regurgitation (MR) and ejection fraction ≥50 percent compared to those with only mild or less MR [35]. At baseline, those with at least moderate MR were more likely to have persistent AF, older age, and larger mitral annular dimension. Of those who had a successful AF ablation with no recurrence during follow-up, 76 percent had a reduction in MR to mild or less, whereas only 18 percent in the group with an AF recurrence had an improvement in MR. In addition, those with an apparently successful ablation were found to have a decrease in left atrial volume, mitral annular dimension, and mitral annular jet area, with no change in ejection fraction or left ventricular end diastolic dimension, though there was a small decrease in left ventricular end systolic dimension. The authors use the term “atrial functional mitral regurgitation” to describe an enlarged left atrium leading to MR in the absence of pathology of the mitral valve, which can improve by AF ablation that decreases left atrial size. The exact relationship to symptoms or mortality associated with this is unknown at the current time.
SUMMARY
●Many patients with atrial fibrillation (AF) develop a modest decline in left ventricular performance that typically returns to the previous baseline following reversion to sinus rhythm.
●The following factors may contribute to the adverse hemodynamic changes in AF:
•A rapid or slow heart rate; if maintained, a chronic tachycardia can lead to a rate-related cardiomyopathy (atrial or ventricular).
•The irregular rhythm.
•Loss of atrial systole required for optimal ventricular filling.
•Activation of neurohumoral vasoconstrictors.
•Increased mitral regurgitation.
●The restoration of sinus rhythm produces a rapid increase in left ventricular systolic performance in most patients with AF. This translates into an improvement in exercise capacity.
●A transient atrial contractile dysfunction may follow cardioversion; it is also known as atrial "stunning.” Atrial stunning may result from a tachycardia-induced atrial cardiomyopathy, which is caused in part by impaired cellular handling of calcium.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
