Peak atrial longitudinal strain is predictive of atrial fibrillation in patients with chronic obstructive pulmonary disease and coronary artery disease

Abstract Background The peak atrial longitudinal strain (PALS) has been validated in the prediction of atrial fibrillation (AF) in the general population. If this finding can be applied to patients with chronic obstructive pulmonary disease (COPD) and concomitant coronary artery disease (CAD) is unknown. Methods and results We analyzed two different study populations of patients with COPD and acute CAD in SCAP trial (Clinical trial.org identifier NCT02324660) and COPD and stable CAD in the NATHAN‐NEVER trial (clinical trial.org identifier NCT02519608). All patients enrolled underwent spirometry and clinical specialistic evaluation to test COPD diagnosis. During the index evaluation, all patients underwent echocardiography. The primary endpoint of the study was the occurrence of AF. Overall, 175 patients have been enrolled. PALS was significantly lower in patients with COPD compared to patients without COPD (26% ± 8% vs. 30% ± 8% for PALS4CV, P = .003). After a mean follow‐up of 49 ± 15 months, 26 patients experienced at least one episode of AF. At multivariable analysis, only PALS (HR: 0.92, 95% CI: 0.86‐0.98, P = .014) resulted as an independent predictor of AF in COPD patients with CAD, with the best cutoff value of 25.5% (sensitivity 87% and specificity 70%). Conclusion The present study confirmed a high incidence of AF events in COPD patients and that PALS is altered and able to independently predict AF in a specific cohort of patients with CAD and COPD. This study points out the need to integrate PALS measurement in the echocardiographic workup of all COPD patients, to early identify those at high risk of AF development.


| INTRODUC TI ON
Cardiovascular diseases (CVDs) are the most prevalent comorbidities in chronic obstructive pulmonary disease (COPD). Not only are CVDs frequent in COPD patients, but they also contribute to disease severity and poor prognosis. 1,2 Coronary artery disease (CAD) and atrial fibrillation (AF) represent the most prevalent CVDs in COPD patients 1 being mutually related diseases as CAD promotes the development and progression of AF. 2 In particular, patients with COPD have a 28% increased risk of developing AF, especially during exacerbations. 3 At the same time, the Atherosclerosis Risk in Communities (ARIC) study showed that the rate of incident AF is inversely associated with flow expiratory volume at first second (FEV1). 4 Previously, by means of specific echocardiographic parameters able to explore right heart function (namely fractional area change and right ventricle strain), we found that smoking patients admitted to hospital for acute coronary syndromes (ACS) with concomitant and previously undiagnosed COPD showed higher right heart dysfunction compared to patients with ACS but without COPD. 5 The data would suggest that COPD can affect right heart functionality through different mechanisms, including pulmonary hypertension and lung hyperinflation, mainly because of hypoxia. At the same time, hypoxia might justify the higher prevalence of atrial fibrillation in patients with COPD that usually have also left atrium dilatation and increased left ventricle (LV) filling pressure that are not consequence of systolic dysfunction, rather to hypoxia-related tachycardia. 6 Secondly, an animal study showed that rabbit with COPD had higher left atrium fibrosis, justifying the increase in atrial fibrillation. 7 The peak atrial longitudinal strain (PALS) during the reservoir phase is a new and adjunctive parameter of the atrial function that reflects the amount of atrial fibrosis and stiffness, factors implicated in atrial fibrillation susceptibility. 8 Previous studies showed that PALS is superior to conventional echocardiographic atrial parameters in predicting AF in the general population. 8 If this finding can be applied to COPD patients with concomitant CAD is unknown. If confirmed, PALS could help discriminate COPD patients at higher risk of developing AF and could contribute to an early diagnosis before embolic complications. Therefore, the aim of the present analysis was to investigate the role of PALS in patients with COPD and CAD in the prediction of AF.

| Study population
The present analysis was carried out by using two different study populations: Screening for COPD in ACS Patients (SCAP) trial (clinical trial.org identifier NCT02324660) and The comparisoN between ticAgrelor and clopidogrel effect on endoTHelial, platelet ANd iNflammation parameters in patiEnts with stable coronary artery disease and chronic obstructiVE pulmonaRy disease undergoing percutaneous coronary intervention (NATHAN-NEVER) trial (clinical trial.org identifier NCT02519608). 9,10 The SCAP trial was a prospective, single-center, investigator-driven study enrolling 137 consecutive patients admitted to hospital for acute coronary syndrome (ACS) with a smoking habit history (smoker or former smoker) between December 2014 and August 2015. Two months after discharge, all patients underwent spirometry and clinical specialistic evaluation to determine the presence of COPD. 9 In the NATHAN-

| Clinical follow-up
All patients underwent periodic clinical visits, and the last follow-up contact was in November 2020 (mean follow-up 49 ± 15 months).
The primary endpoint of the present study was the occurrence of at least one episode of AF in patients with CAD and concomitant COPD. The occurrence of stroke was also assessed. Univariate and multivariable Cox regression analysis was performed to assess the prognostic value of PALS for AF in COPD patients. Clinical and echocardiographic variables included in Table 1 with P < .

| Population characteristics
Overall, 175 patients have been included in the present analysis ( Figure 1).

| Peak atrial longitudinal strain and atrial fibrillation
PALS4CV was significantly lower in patients with COPD compared to patients without COPD (26% ± 8% vs. 30% ± 8% for PALS4CV, P = .003, Table 1). Considering the other echocardiographic parameters, LV global longitudinal strain (LVGLS), indexed left atrial volume, RVS, and FAC significantly differed in the two groups (Table 1). At the follow-up, 30 patients experienced at least one episode of AF.
Most of the events occurred in patients with concomitant COPD (26 events vs four events in patients with vs without COPD) ( Table 1) the best cutoff value of 25.5% (sensitivity 87% and specificity 70%, Figure 2). Repeating multivariable Cox regression analysis with the PALS4CV cutoff <25.5%, this resulted as a strong predictor for AF (HR = 6.68, 95% CI 1.76-25.31, P = .005, Figure 3).

| D ISCUSS I ON
The present study confirmed a high incidence of AF events in COPD patients with CAD. Also, PALS is altered and able to independently predict AF in a specific cohort of patients with acute (SCAP) or sta-

| CON CLUS IONS
Peak atrial longitudinal strain is altered and able to independently predict AF in a specific cohort of patients with CAD and COPD. This study points out the need to integrate a marker as PALS measurement in the echocardiographic workup of all COPD patients, to early identify those at high risk of AF development.

ACK N OWLED G M ENTS
None.

CO N FLI C T O F I NTE R E S T S
None declared.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request. Note: Clinical and echocardiographic variables included in Table 1 with P < .1 after stratification for the presence of atrial fibrillation in patients with CAD and COPD were included in univariate analysis; only variables with P < .05 were included in multivariable model.