Atrial Fibrillation Incidence in Left Ventricular Assist Device Patients

Atrial arrhythmias are common in patients with heart failure following LVAD implantation. In observational studies, up to 70% of LVAD patients developed AF or atrial flutter (AFL) following LVAD surgery. The majority of these patients had preimplantation AF due to chronic structural heart disease and left atrial dilation, but approximately 10% to 15% developed de novo AF after implantation. Risk factors associated with de novo AF include female sex, increased age, renal insufficiency, and lung disease. ^, Interestingly, 40% of patients with paroxysmal AF prior to an LVAD may experience AF remission, which may be attributed to a decrease in left ventricular size and volume index with an LVAD. ^,

Atrial Fibrillation Incidence in Orthotopic Heart Transplant Patients

The incidence of AF after orthotopic heart transplantation is less frequent than in LVAD patients but still occurs. AF has been reported in 10% to 20% of OHT recipients, with about half the cases occurring in the early postoperative period. The incidence of AF after OHT surgery is also lower than the incidence of AF after other major cardiothoracic operations, such as coronary artery bypass grafting, valve replacement, or lung transplants (15%–60%). One possible explanation for this difference is that patients who undergo OHT receive healthy donor hearts compared to patients undergoing other types of cardiac surgery, who have experienced years of cardiac remodeling due to ischemic and valvular disease. However, the difference can also be explained by the surgical procedure itself. Orthotopic heart transplantation surgically isolates electrically active foci in the pulmonary veins, such that a barrier is created between electrical triggers in the pulmonary veins and susceptible myocardium. ^{, , ,} OHT surgery also results in complete cardiac denervation, which decreases AF incidence by eliminating parasympathetic input to the intrinsic cardiac nervous system. ^{, , , , , ,}

The donor–recipient anastomosis technique may also play a role in susceptibility to AF. In recent years, bicaval (BC) anastomosis, where the donor heart is anastomosed to the 2 vena cavae, the great vessels, and the left atrial cuff, has become a more popular technique compared to the traditional biatrial (BA) anastomosis technique because it better preserves the morphology and function of the atrium, reducing the incidence of atrial arrhythmias. ^{, ,} Donor-to-recipient anastomosis using the original BA technique, where part of the recipient right and left atria are retained and sutured to the right atrium of the donor, can lead to atrial dilation and increased right atrial pressure, in particular, which promotes re-entrant tachycardia, atrial ectopic rhythms, and fibrillation. A retrospective single-center study comparing the incidences of early postoperative AF among different surgical techniques for orthotopic heart transplantation reported only a slighter higher AF incidence of 17.4% for the BA technique compared to 14.8% for the BC technique. The BA technique is more likely to engender AF in the long term. ^, In both surgical techniques, donor to recipient conduction seems to occur as a result of electrical propagation along viable myocardium bridging the surgical lines.

Atrial Fibrillation Outcomes in Left Ventricular Assist Device Patients

Despite its high prevalence, postoperative AF in LVAD patients has not been shown to be associated with an increased risk of mortality, stroke, or bleeding. ^, However, it may impair quality of life, reduce functional capacity, and lead to more frequent hospitalizations for LVAD patients. Persistent AF is associated with worse outcomes compared to paroxysmal AF. ^, In patients with the HeartMate II device (Abbott, Green Oaks, IL, USA), persistent AF was an independent predictor of the composite endpoint of death and heart failure hospitalization, while paroxysmal AF was not. Thromboembolic events are also of major concern in LVAD patients with AF as both conditions increase clotting propensity. Studies have shown inconsistent data on whether AF, preoperatively or postoperatively, is associated with an increased risk of stroke or device thrombosis. ^{, , ,} Stulak and Deshmukh and colleagues reported that in patients with preoperative and 30 day postoperative AF, there was less freedom from thromboembolic events 1 to 2 years post-LVAD. However, several other studies have reported no increased thromboembolic events in patients with preoperative or postoperative AF across the same follow-up period. ^{, , , ,}

Atrial Fibrillation Causes and Outcomes in Orthotopic Heart Transplant Patients

In the immediate postoperative period, nongraft-related causes of AF are more prevalent and signal a more benign etiology. Surgical factors such as prolonged graft ischemia causing endocardial fibrosis, surgical trauma, and pericarditis all incite AF, and it is current standard of care to minimize ischemia time. ^, Postoperative inotropic support may also increase adrenergic tone and stimulate AF development. Noncardiac causes of AF are also possible, including electrolyte imbalances from surgery that can be exacerbated by immunosuppressants, as well as thyroid dysfunction following surgery. However, early graft failure with acute allograft rejection still remains quite common and contributes to about one-third of cases. ^, Improved surgical skills and techniques, better preservation of organs, and effective immunosuppressant therapy have as a whole decreased the rates of postoperative AF, mostly by curbing surgical complications and acute cellular rejection. Current 30 day estimates of AF following orthotopic heart transplantation are between 0.9% and 11%.

In intermediate-late onset AF or persistent AF, chronic rejection, coronary allograft vasculopathy, and heart failure are to be suspected because AF is rare in a stable transplant patient. ^{, , ,} Ventricular fibrosis may cause diastolic dysfunction with elevated filling pressures leading to atrial stretch and AF. Prompt evaluation with echocardiography, endomyocardial biopsy, and angiography should be conducted. ^, An atrial conduction defect, seen as an increase of the terminal force of the P wave in lead V1, can predict the occurrence of AF in chronic rejection with a sensitivity and specificity of approximately 90%. Cases of late onset AF without rejection or vasculopathy have also been reported in the literature. The underlying mechanism of AF is unclear in these cases, but one proposition is that it could be driven by other systemic conditions, such as renal failure or infections. ^, Sympathetic and parasympathetic re-enervation of cardiac tissue, which takes months to years and occurs in a heterogenous manner, may also predispose to AF. Left ventricular systolic dysfunction may occur from tachycardia-mediated cardiomyopathy in persistent AF and is reversible with aggressive rate and rhythm control of AF.

In general, hospitalizations with a primary diagnosis of AF are infrequent among OHT patients, occurring less than 1% of the time. They are associated with a low in-hospital mortality rate of 2.3% with 1% event rates for stroke and gastrointestinal bleeding. Although AF may not directly cause significant morbidity and mortality in this population, it has been associated with increased frailty and serves as a predictor of higher all-cause mortality, especially if late onset. ^{, , ,}

Atrial Fibrillation Treatment in Left Ventricular Assist Device Patients

Presently, there are limited data to guide optimal management of AF in LVAD patients. Medical management strategies for both rate and rhythm control have been extrapolated from the non-LVAD population and small retrospective studies, acknowledging that the underlying physiology may be different in LVAD patients. The AHA/ACC guidelines primarily recommend rate control for patients with LVADs, citing the benefits of beta-blockers for controlling heart rate and improving outcomes in patients with heart failure. ^, In cases of hemodynamic instability or symptomatic AF, rhythm control with amiodarone is considered appropriate due to its effectiveness and lack of proarrhythmic risk. The ESC guidelines are somewhat more balanced between rate and rhythm control, acknowledging that in some patients, rhythm control may improve hemodynamic function and quality of life, particularly in cases of symptomatic AF or rapid ventricular rates that affect LVAD function. ^, The ESC guidelines also recommend amiodarone as a first-line agent but provide more flexibility in the use of other AADs in specific cases, such as sotalol or dronedarone, which are generally discouraged due to their less-favorable safety profiles in patients with heart failure ( Table 1 ).

Table 1

Management strategies for atrial fibrillation in left ventricular assist devices and orthotopic heart transplants per the American Heart Association/the American College of Cardiology, and the European Society of Cardiology guidelines

Patient Group	Management Category	AHA/ACC Recommendations	ESC Recommendations	References
LVAD	Antiarrhythmic drugs	Amiodarone is preferred due to efficacy and lower proarrhythmic risk; other AADs like sotalol discouraged	Amiodarone is the first-line agent but allows flexibility for other AADs under close monitoring	January et al, 2014, January et al, 2019
	Anticoagulation	Routine anticoagulation with VKAs (warfarin), target INR 2.0–3.0; individualized adjustments based on patient condition and complications	Similar to AHA/ACC but more open to DOAC use in certain stable, low-risk patients, though caution is advised	January et al, 2014, January et al, 2019
	Catheter Ablation	No specific emphasis in guidelines	Considered as a treatment option in refractory AF, particularly in symptomatic patients	Yancy et al, 2017, January et al, 2019
	Rate vs rhythm control	Primarily recommend rate control with beta-blockers; rhythm control with amiodarone if symptomatic or unstable	More balanced between rate and rhythm control; rhythm control considered beneficial for symptomatic or hemodynamically affected patients	January et al, 2014, Yancy et al, 2017
OHT	Antiarrhythmic drugs	Amiodarone is preferred due to interactions with immunosuppressants; reserved for symptomatic or unstable AF	Amiodarone preferred, but flexibility with AADs under close monitoring; catheter ablation considered in refractory cases	Hindricks et al, 2021, Ponikowski et al, 2016
	Anticoagulation	Individualized anticoagulation based on thromboembolic risk, hemodynamic status, and rejection risk	Individualized anticoagulation; emphasizes monitoring drug interactions, especially with immunosuppressants	Hindricks et al, 2021, Ponikowski et al, 2016
	Catheter ablation	Reserved for refractory cases, not primary treatment strategy	Emphasizes catheter ablation as an option for refractory or symptomatic cases	Hindricks et al, 2021, Ponikowski et al, 2016
	Rate vs rhythm control	Cautious rate control with beta-blockers or calcium channel blockers; individualized rhythm control based on patient response	Emphasis on rhythm control in symptomatic patients; catheter ablation considered in refractory cases	Hindricks et al, 2021, Ponikowski et al, 2016

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