Substantial prevalence of subclinical cardiovascular diseases in patients with hemophilia A evaluated by advanced electrocardiography

Background: Patients with hemophilia A (PWHA) have reportedly lower mortality due to cardiovascular disease (CVD) compared to the general population.

Aim: To evaluate signs of CVD in asymptomatic PWHA using advanced electrocardiography (A-ECG).

Methods: PWHA (n = 29, median [interquartile range] age 57 [47-70] years) and age-matched male controls (n = 29, 59 [48-68] years) were evaluated. Digital resting 12‑lead ECGs were retrospectively analysed using both conventional and A-ECG techniques including derived vectorcardiography and waveform complexity. Previously validated multivariate A-ECG scores designed to detect: 1) cardiac disease in general, 2) left ventricular systolic dysfunction (LVSD), 3) coronary artery disease or coronary microvascular disease (CAD/CMVD), or 4) left ventricular hypertrophy defined as left ventricular electrical remodelling (LVH/LVER), were quantified and compared between PWHA and controls.

Results: Compared to controls, PWHA had a higher probability of having cardiac disease (median [interquartile range] 84.6 [32.5-99.5] vs. 0.6 [0.2-8.2]%), LVSD (4.1 [1.3-12.9] vs. 0.9 [0.5-3.2]%), CAD/CMVD (84.3 [35.6-96.6] vs. 6.7 [0.8-24.4]%), and LVH/LVER (17 [5/29] vs. 0 [0/29]%). Compared to patients with non-severe HA (n = 20), patients with severe HA (n = 9) showed a non-significant trend towards lower probability of cardiac disease, CAD/CMVD, LVSD and LVH/LVER.

Conclusion: In PWHA, A-ECG exhibits changes more indicative of overt or subclinical CVD compared to controls, and there is a tendency for lower scores for CVD in patients with severe compared to non-severe HA. These results suggest that PWHA ≥ 40 years could be at higher risk for CVD than age-matched controls and that A-ECG could potentially be used for early detection.