Sex and gender differences in patients undergoing ablation of atrial arrhythmias

Background: Women and men differ in the prevalence of arrhythmias. Furthermore, there are sex and gender differences in referral for ablation, symptom severity, health-related quality of life (HRQOL), functional impairment and response to treatment, risk factors, and outcomes.

Aim: This thesis studies sex and gender differences in referral, treatment, outcome, symptom, HRQOL, and functional impairment in patients undergoing cardiac ablation of atrial fibrillation and paroxysmal supraventricular tachycardia (PSVT).

Method: The thesis is based on four studies. Study I and II are observational prospective studies based on questionnaires before and six months after ablation. Study I include 214 (109 women) patients referred for PSVT ablation and Study II includes 242 (121 women) patients with atrial fibrillation referred for pulmonary vein isolation (PVI). The following questionnaires were used: Symptom Checklist: Frequency and Severity, Short Form 36, and Sickness Impact profile. Referral patterns and socio-economic data and symptom duration were evaluated with a separate questionnaire. In Study III, 700 patients (359 women) who had undergone AV-nodal junction (AVJ) ablation between 1990 and 2010 were retrospectively studied. Data were sampled from medical records, the Swedish ICD and Pacemaker Registry, and from the National Patient Registry kept by the National Board of Health and Welfare. Study IV was conducted with 80 (40 women) patients randomized either to an active or a standard pain treatment during PVI using cry-or radiofrequency energy. Evaluation of the two treatments strategies was assessed with a questionnaire based on the Pain-O-Meter.

Results: In Study I, although women had more PSVT symptoms, they were referred in mean six years later than the men. In addition, women more often reported they were not believed when describing their arrhythmia symptoms and were consequently more often diagnosed with stress and anxiety. In Study II, no such sex difference was found, but women were more symptomatic, assessed a lower HRQOL and a greater functional impairment than the men. Furthermore, women more often received drug treatment and were less often than men referred for cardioversion before ablation. In Study III, heart failure was present in more men than women before the AVJ ablation. When indication presented before ablation, women less often than men received implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy (CRT). There were no differences between the sexes regarding primary cause of death, and cardiovascular mortality was the most common cause of death. The main parameter influencing survival was age at the time of AVJ ablation. In Study IV, over 90% of the patients experienced pain during the PVI. Premedication and regular administration of analgesic resulted in less pain and fewer drug administration occasions. Women experienced more pain than men regardless of energy type, cryo - or radiofrequency energy.

Conclusion: All four studies showed that there were sex and gender difference in either referral, morbidity, symptom, HRQOL, functional impairment or response to treatment. Women with PSVT and atrial fibrillation were treated more conservatively than men. Women with PSVT were referred for curative ablation later than men despite having more symptoms. Symptoms due to PSVT in women were more often incorrectly diagnosed as panic attacks, stress, anxiety, or depression. Furthermore, women with atrial fibrillation were more symptomatic, assessed a lower HRQOL and a greater functional impairment but despite that, were more seldom referred for cardioversion before PVI. Women less often received CRT or ICD implantation even when indication was present before AVJ ablation. We found no sex differences regarding survival or primary cause of death after AVJ ablation. The main factor influencing survival was age at the time of ablation. Women experienced more pain than men during PVI, but an active regular supply of analgesic and sedative drugs reduced pain and discomfort during PVI in both sexes.

List of scientific papers

I. Carnlöf C, Iwarzon M, Jensen-Urstad M, Gadler F, Insulander P. Women with PSVT are often misdiagnosed, referred later than men, and have more symptoms after ablation. Scand Cardiovasc J. 2017 Dec;51(6):299-307.
https://doi.org/10.1080/14017431.2017.1385837

II. Carnlöf C, Iwarzon M, Jensen-Urstad M, Gadler F, Insulander P. Gender differences in referral, symptoms, HRQOL and functional impairment in patients with atrial fibrillation before and after for pulmonary vein isolation. [Manuscript]

III. Carnlöf C, Insulander P, Jensen-Urstad M, Iwarzon M, Gadler F. Atrio-ventricular junction ablation and pacemaker treatment: a comparison between men and women. Scand Cardiovasc J. 2018 Jun;52(3):120-126.
https://doi.org/10.1080/14017431.2018.1446549

IV. Carnlöf C, Insulander P, Jensen-Urstad M. An active supply of analgesics during pulmonary vein isolation reduces pain. Scand Cardiovasc J. 2014 Feb;48(1):35-40.
https://doi.org/10.3109/14017431.2013.859296