Baseline Characteristics and Treatment
We enrolled 343 patients in the study; 175 (51%) were female and 168 (48%) male. Descriptive analysis reveals that females were significantly older than males (p < .001) with a mean age of 69.30 ± 11.9 [27–91] vs. 57.79 ± 14.8 [21–87].
Males and females were significantly different in terms of cardiovascular risk profile. Females had a higher mean BMI score (32.65 ± 6.9 vs. 29.37 ± 4.6, p < .001, OR 0.9) and a higher rate of co-morbidities as hypertension (p < .001) hyperlipidemia (p = 0.01), diabetes mellitus (p = 0.05), and valvular heart disease (p = 0.05). On the other hand, Males had a higher rate of coronary artery disease (p < .001) and heart failure with a reduced ejection fraction (p < .001). As a result, females had a higher mean score of CHADS2 (1.85 ± 1.3 vs. 1.23 ± 1.2) and CHA2DS2-VASc (3.61 ± 1.7 vs. 1.79 ± 1.7) than males (p < .001 for both).
Females also had a significantly higher prevalence of thyroid dysfunction than males (18.3% vs. 1.8%, OR 0.08, p < .001) and used antiarrhythmic medication less frequent (24.0% vs. 42.8%, p < .001) [Table 2].
Table 2
Sex difference in patient’s baseline characteristics (univariate analysis)
Patient Characteristic | All study population N = 343 | Female N (%) = 175 (51) | Male N (%) = 168 (48) | P-value | OR | 95 CI% |
Age | 63.67 ± 14.6 [21–91] | 69.30 ± 11.9 [27–91] | 57.79 ± 14.8 [21–87] | < .001 | 0.93 | 0.92–0.95 |
CHA2DS2-VASc Score | 2.72 ± 1.9 [0–8] | 3.61 ± 1.7 [0–8] | 1.79 ± 1.7 [0–7] | < .001 | 0.69 | 0.58–0.82 |
CHADS2 Score | 1.55 ± 1.3 [0–6] | 1.85 ± 1.3 [0–6] | 1.23 ± 1.2 [0–6] | < .001 | 0.55 | 0.47–0.64 |
BMI | 31.05 ± 6.1 [19–56] | 32.65 ± 6.9 [19–56] | 29.37 ± 4.6 [20–41] | < .001 | 0.90 | 0.87–0.94 |
Hypertension | 217 (63.1) | 123 (73.3) | 88 (52.4) | < .001 | 0.4 | 0.25–0.62 |
Hyperlipidemia | 202 (58.7) | 114 (64.8) | 88 (52.4) | 0.01 | 0.59 | 0.38–0.92 |
Diabetes Mellitus | 116 (33.7) | 67 (38.1) | 49 (29.2) | 0.05 | 0.67 | 0.42–1.05 |
Coronary artery disease | 67 (19.5) | 14 (8.0) | 53 (31.5) | < .001 | 5.33 | 2.82–10.06 |
Peripheral Vascular Disease | 11 (3.2) | 3 (1.7) | 8 (4.8) | 0.09 | 2.86 | 0.74–10.99 |
CVA | 37 (10.8) | 22 (12.5) | 15 (8.9) | 0.18 | 0.68 | 0.34–1.36 |
Heart Failure | | < .001 | 7.73 | 2.93–20.43 |
HFREF | 26 (7.6) | 0 (0) | 26 (15.5) |
HFPEF | 15 (4.4) | 13 (7.4) | 2 (1.2) |
Mixed Type | 10 (2.9) | 5 (2.8) | 5 (3.0) |
Thyroid dysfunction | 35 (10.2) | 32 (18.3) | 3 (1.8) | < .001 | 0.08 | 0.02–0.27 |
Valvular Heart Disease | 24 (7.0) | 17 (9.7) | 7 (4.2) | 0.05 | 0.4 | 0.16-1.00 |
Chronic renal failure | 32 (9.3) | 18 (10.2) | 14 (8.3) | 0.33 | 0.79 | 0.38–1.66 |
Chronic use of medication | |
Warfarin | 42 (12.2) | 26 (14.9) | 16 (9.5) | 0.09 | 0.82 | 0.44–1.53 |
NOAC | 99 (28.8) | 60(34.1) | 39 (23.2) | 0.03 | 0.58 | 0.36–0.94 |
Calcium Chanel blockers | 17 (4.9) | 9 (5.1) | 8 (4.8) | 1.00 | 0.92 | 0.34–2.46 |
Beta-blockers | 184 (53.5) | 107 (60.8) | 77 (45.8) | 0.04 | 0.54 | 0.35–0.83 |
Anti-platelet | 81 (23.5) | 28 (15.9) | 53(31.5) | < .001 | 2.43 | 1.45–4.09 |
Anticoagulation and Antiplatelet | 34 (9.9) | 16 (9.1) | 18 (10.7) | 0.38 | 1.19 | 0.58–2.42 |
Antiarrhythmic agents | 114 (33.2) | 42 (24.0) | 72 (42.8) | < .001 | 2.41 | 1.13–4.16 |
BMI, Body mass index; HFREF, Heart failure with reduced ejection fraction; HFPEF, Heart failure with preserved ejection fraction; NOAC, New oral anticoagulation. |
Highlighted cells denoate a statisticallty siginifican values. |
A sex-based difference was also observed regarding presenting symptoms, admission, and treatment strategy. Females tend to seek medical care much longer (p = 0.01) than males, and more than 10% of the females present with atypical symptoms such as weakness, dizziness, and dyspnea (p = 0.01).
More AF Females tends to be treated with a rate control agent as a sole treatment for rhythm conversion as compared to males (44.9% vs. 20.8%, p < .001, OR 2.55, 95% CI 1.79–3.63) and the use of electrical cardioversion was much lower (7.4% vs. 22%). Consequently, the success rate and the recovery of the sinus rhythm was lower in females (73.9% Vs. 89.9%, p < .001) [Table 3].
Table 3
Sex difference in patient’s treatment and outcome (univariate analysis)
Characteristics | All study population N = 343 | Female N (%) = 175 (51) | Male N (%) = 168 (48) | P-value | OR | 95 CI% |
Hemodynamic instability | 9 (2.6) | 6 (3.4) | 3 (1.8) | 0.50 | 0.51 | 0.12–2.09 |
Sign of HF at admission | 18 (5.2) | 13 (7.4) | 5 (3.0) | 0.08 | 0.38 | 0.13–1.10 |
Duration of symptoms | | 0.01 | 0.53 | 0.31–0.88 |
< 24h | 263 (76.5) | 125 (71.0) | 138 (82.1) |
> 24h | 81 (23.5) | 51 (29.0) | 30 (17.9) |
Atypical symptoms | 27 (7.8) | 20 (11.4) | 7 (4.2) | 0.01 | 0.33 | 0.13–0.82 |
Treatment Strategy | | < .001 | 2.55 | 1.79–3.63 |
Rate control only | 114 (33.1) | 79 (44.9) | 35 (20.8) |
Rhythm control agent | 180 (52.3) | 84 (47.7) | 96 (57.1) |
Cardioversion | 50 (14.5) | 13 (7.4) | 37 (22.0) |
Sinus recovery | 281 (81.7) | 130 (73.9) | 151 (89.9) | < .001 | 3.14 | 1.71–5.74 |
Hospitalization | 124 (36.0) | 79 (44.9) | 45 (26.8) | < 0.01 | 0.44 | 0.28–0.70 |
Outcome | |
CVA/TIA | 12 (3.5) | 10 (5.7) | 2 (1.2) | 0.03 | 0.2 | 0.43–0.92 |
Heart Failure hospitalization | 26 (7.6) | 22 (12.5) | 4 (2.4) | < .001 | 0.17 | 0.05–0.50 |
Myocardial Infarction | | 0.01 | 0.47 | 0.42–0.53 |
STEMI | 9 (2.6) | 0 (0) | 9 (5.4) |
Non-STEMI | 4 (1.2) | 4 (2.3) | 0 (0) |
VTE | 1 (0.3) | 1 (0.6) | 0 (0) | 1.00 | 0.51 | 0.46–0.56 |
Recurrent AF | 97 (28.2) | 59 (33.5) | 38 (22.6) | 0.03 | 0.58 | 0.35–0.93 |
Death | 9 (2.6) | 6 (3.4) | 3 (1.8) | 0.54 | 0.51 | 0.12–2.09 |
Cumulative events | 127 (36.9) | 77 (43.8) | 50 (29.8) | 0.08 | 0.54 | 0.34–0.85 |
Outcomes
There were 52 (15.16%) cases of MACE, with 12 (3.5%) having CVA, 26 (7.6%) HF admissions, 1 (0.3%) Pulmonary embolism (PE) or Deep vein thrombosis (DVT) and 13 (3.79%) IHD admissions. Unadjusted univariate analysis shows that females had higher heart failure hospitalization, recurrent AF, and CVA than males and had less risk for myocardial infarction [Table 3]. However, following multivariate analysis of adjusting sex to age and co-morbidities (the full list of adjusted variables appears in the statistical analysis paragraph), CVA and myocardial infarction are no longer remain significantly [Figure 1].
Females exhibited a higher rate of HF events than males (OR 2.73, χ2 11.09, P-value < 0.001, 95% CI 1.04–5.89) and had shorter mean days-to-HF hospitalization (87.45 ± 8.74 vs. 164.5 ± 18.80, HR 5.72, P-value = 0.09, 95% CI 1.30-25.05) [Figure 2]. Females also had a higher incidence of recurrent AF events (OR 3.86, χ2 5.06, P-value = 0.02, 95% CI 1.18–12.61) and a shorter time-to-AF (108.10 ± 10.81 vs. 160.52 ± 18.0, p = 0.01, HR 1.70, 95% CI 1.11–2.60, for mean days) [Kaplan-Mayer survival curve, Fig. 3]. Thyroid dysfunction was found to be an independent risk factor for recurrent AF (OR 5.95, χ2 27.94, P value < 0.001, 95% CI 3.15–9.73) [Table 4] and was associated with shorter time-to-AF (74.16 ± 15.29 vs. 112.00 ± 15.36, meantime in days) [Kaplan-Mayer survival curve, Fig. 4].
Table 4
Gender and non-gender based outcome (multinomial regression analysis)
Outcome | Independent risk factor X | Odds ratio | Chi-square | P-value | 95 CI% |
Gender-based risk factors |
Heart Failure | Female | 2.73 | 11.09 | < 0.001 | 1.04–5.89 |
Recurrent AF | Female | 3.86 | 20.27 | 0.02 | 1.18–12.61 |
Death | Female ≥ 75 years | 1.60 | 20.16 | < .001 | 1.2–3.4 |
Non-Gender-based risk factors |
Recurrent AF | Rate control treatment | 3.42 | 17.18 | < .001 | 1.81–6.46 |
Recurrent AF | Thyroid dysfunction | 5.95 | 27.94 | < .001 | 3.15–9.73 |
CVA | Rate control treatment | 7.49 | 36.18 | < .001 | 2.44–16.12 |
Death | HF on admission | 5.8 | 7.39 | 0.02 | 0.39–98.60 |
Multivariate analysis was done to all of the following factors: hypertension, hyperlipidemia, diabetes mellitus, heart failure at baseline, thryoid dysfunction, chronic use of beta-blocker, anti-arrythmic drugs, anticoagulation and antiplatet treatment and treatment strategy. CHADS2 and CHA2DS2-VASc scores were excluded from analysis due to collinearity collison problem. |
The presence of atypical symptoms as nausea, dizziness, weakness, and dyspnea correlated with higher risk for recurrent AF (OR 4.09, χ2 5.17, P-value = 0.02, 95% CI [1.08–15.41]) and HF hospitalization (OR 3.93, χ2 3.75, P-value = 0.05, 95% CI [1.34–6.87].
During follow-up, 9 (2.62%) patients died, six female and three males. The mortality rate among females and males was nonsignificant. Nevertheless, subgroup analysis revealed that females ≥ 75 years of age had a significantly higher risk for death, in comparison with males of the same age (OR 1.60, χ2 20.16, P < .001, 95%CI 1.2–3.4) [Table 4], and the survival time was much shorter (HR 63.35, χ2 4.19, P-value = 0.04, 95% CI 0.03-108.78) [Figure 5]. Heart failure on admission was an independent factor for death in both males and females regardless of age (OR 5.8, χ2 7.39, P value = 0.02, 95% CI [0.3–95.60]).
Correlation between Treatment Strategy and Outcomes
The use of a rate control strategy as a sole treatment for AF conversion, followed by rate control medication for maintenance was associated with a higher rate of recurrent AF (OR 3.42, χ2 17.18, P-value < 0.0001, 95% CI [1.81–6.46] and CVA (OR 7.49, χ2 36.18, P-value < 0.0001, 95% CI [2.4-16.12]), regardless of treatment success or sex.