Increase in atrial fibrillation-related mortality in the United States during the COVID-19 pandemic.

The COVID-19 pandemic has generated more excess deaths due to both COVID-19 and other clinical conditions, such as cardiovascular disease. The relationship between atrial fibrillation (AF) and COVID-19 infection is complex. Indeed, AF has resulted to be associated with significantly increased risk of short-term mortality in patients infected by SARS-CoV-2 [2]; furthermore, COVID-19 patients, per se, have an increased risk to develop AF [3]. Aim of the present manuscript is to investigate the trend of AF-related mortality in US before and during the COVID-19 pandemic. For this purpose, de-identified mortality data regarding the multiple cause-of-death, between 2015 and 2020, provided by the Centers for Disease and Control (CDC) through the free-platform CDC WONDER were used [4]. ICD-10 codes related to AF (I48.x) or COVID-19 (U07.1), in any position of death certificates, were adopted to identify patients suitable for the analysis. AF-related age-adjusted mortality rates (with corresponding 95% confidence interval -CI-) and relative trends (calculated as average annual percent change -AAPC-) were analyzed using Joinpoint regression (Joinpoint, version 4.6.0.0, National Cancer Institute, USA) to analyze changes in trends, if any, over the years. Sub-group analysis based on gender, age >65 years and race were also carried out. Due to the publicly available and de-identified nature of the data, no ethic approval was required for the present study.

During the 2020, 263.431 deaths due to AF were registered in US. Of these, 217.279 and 46.152 were recorded in subjects without and with COVID-19 infection, respectively. In that year, the overall age-adjusted AF-related mortality rate was 52.2 (95% CI: 52.0-52.4) and 11.1 (95% CI: 11.0-11.2) per 100 000 population in individuals with and without COVID-19 infection, respectively. The proportionate mortality of AF in deaths with COVID-19 was 17.5%. During the pandemic, the age-adjusted mortality rate resulted significantly higher, as per Jointpoint regression, [AAPC 5.1 (95% CI: 3.3-7.0), p<0.0001), compared to that observed over the 2019 [44.8 per 100 000 (95% CI: 44.6-45.0)] and 2018 [43.7 per 100 000 (95% CI: 43.5-43.9)], resulting in an increase of 43.3% and 50.2%, respectively. Moreover, the AF age-adjusted mortality rate resulted higher in men over the study period (Figure 1 ). Regarding the AF-related deaths with COVID-19 during the 2020, the age adjusted mortality rates were higher in men versus woman [14.7 (95% CI: 14.5-14.9) vs 8.5 (95% CI: 8.4-8.6) per 100 000], among white versus black population [ 11.4 (95% CI: 11.3-11.5) vs 11.1 (95% CI: 10.7-11.4) per 100 000] and in subjects aged more 65 years old [14.5 (95% CI: 14.4-14.7) vs 7.3 (95% CI: 7.1-7.5) per 100 000]. AF-related deaths were observed in 93.4% of patients aged more than 65 years old.

Figure 1

Age-adjusted atrial fibrillation related mortality in US between 2015 and 2020 (first year of the COVID-19 pandemic)

During the first year of COVID-19 pandemic, an excess mortality for AF was observed in US. As evidenced by our sub-analyses, this phenomenon mainly affected white males aged more than 65 years old while the difference among whites and African Americans was not so obvious as demonstrated by the overlap of the confidence intervals. Indeed, Blacks were less frequently hospitalized for COVID-19; this phenomenon contributes to the underestimation of AF [5]. Notably, a swift increase in the AF-related mortality was observed during the entire study period but this trend did not reach the statistical significance until the COVID-19 outbreak. Probably, all the provided data may have underestimated the real impact of AF in 2020, especially during the early phase of the pandemic, for the presence of undiagnosed cases and for potential miscoding being our analysis based on death certificates. Moreover, the rates of underling comorbidities, sex ratios and age distribution may be different from those present in other regions of the world, limiting the generalizability of our findings. Finally, no data were available regarding the AF-related mortality in patients with long-COVID syndrome. Present findings reinforce the need for additional screening and public health care interventions to identify AF in the general population remembering the prognostic impact of this arrhythmia in COVID-19 patients.

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