Background: Areas of conduction disorders play an important role in both initiation and perpetuation of AF and can be recognized by specific changes in unipolar potential morphology. For example, EGM fractionation may be caused by asynchronous activation of adjacent cardiomyocytes because of structural barriers such as fibrotic strands. However, it is unknown whether there are sex differences in unipolar potential morphology. Therefore, atrial potential morphologies during sinus rhythm (SR) were compared between male and female patients. Methods: Based on propensity score matching, 62 male and female patients in whom high-resolution mapping of the right atrium (RA), left atrium (LA), and pulmonary vein area (PVA) including Bachmann's bundle (BB) was performed during coronary bypass grafting surgery and/or valvular heart surgery. Unipolar potentials were classified as single potentials (SPs), short double potentials (SDPs), long double potentials (LDP), fractionated potentials (FPs) and fraction duration (FD). The proportion of conduction block lines was also determined. Results: Female patients had a higher proportion of SDPs, LDPs and FPs at the RA, and SDPs at BB. At the PVA, there were less SPs and more SDPs and FPs. In females, FDs were longer at the RA and PVA, and potential voltages of only SPs were lower at the RA (all P < 0.05). Females also had more CB at the RA and at PVA (P < 0.05). Conclusion: In females, the proportion of single unipolar potentials indicative of smooth conduction, was lower compared to males, at the RA and PVA and to a lesser degree at BB. Females also had more CB at RA and PVA. Hence, these results may reflect sex-differences in the degree of electrical remodeling.

Background: Aging induces structural remodeling, altering atrial electrogram morphology. Over time, structural and consequently electrical remodeling creates a substrate for atrial fibrillation. In structural heart disease, age-induced remodeling comes on top of a pre-existing degree of structural remodeling due to pressure or volume overload. Objective: Investigate the severity of age-related electrical remodeling in patients undergoing surgery for structural heart disease by utilizing a high resolution epicardial mapping approach. Methods: Five seconds of sinus rhythm were recorded intraoperatively at the right atrium (RA), Bachmann's bundle (BB), the left atrium, and the pulmonary vein area. Potential voltage, low-voltage area (LVA) and conduction velocity (CV) were assessed in all regions. Results: 104 patients were included (62,5 % male, age: 26–84 years) and categorized in three age groups: young-age (age <60 years, n = 40), middle-age (age 60–71 years, n = 33), or old-age (age ≥72 years, n = 31) group. Compared to the young-age group, the old-age group had 1) lower median potential voltages at RA (4.65 [3.53–5.62]mV versus 5.94 [4.86–6.79]mV, p = 0.001) and 2) lower CV at RA (87.86 [82.53–96.67]cm/s versus 94.81 [90.14–98.59]cm/s, p = 0.016) and BB (83.38 [67.72–94.96]cm/s versus 98.84 [86.58–102.90]cm/s, p = 0.005). Conclusions: Age-related electrophysiological changes in patients with structural heart disease include reduction in atrial potential voltages and slowing of CV. These changes were less pronounced in the middle-age group. This indicates that electrical remodeling is a combination of both the underlying heart disease and the aging process. However, the less pronounced changes in the middle-age group may reflect a more gradual progression of age-related remodeling.

Background: There is increasing evidence that presentation, progression, and management of atrial arrhythmias, such as atrial fibrillation (AF), differ between women and men. Bachmann’s bundle (BB) is the main route for interatrial conduction, and sex-related differences in structural and electrical remodeling of BB may contribute to differences in AF development between women and men. Objective: Investigate whether sex differences in the electrophysiological properties of BB assessed by high-resolution and density maps exist in patients with AF. Methods: Sinus rhythm at BB was recorded for 5 s during cardiac surgery. Potential voltage, low-voltage area (LVA), conduction heterogeneity, unipolar potential morphology, and conduction velocity were assessed for both men and women. Results: The study population consisted of 108 patients (73 men, 35 women). Women had significantly lower potential voltages (5th percentile: 0.7 mV [0.6–1.0] vs 1.1 mV [0.6–1.4], p = 0.028), more LVAs (10.8% [4.6–19.7] vs 4.3% [2.2–11.7], p = 0.012) and more long double potentials (11.1% [3.6–13.5] vs 5.0% [1.0–10.3], p = 0.015) compared to men. Conclusions: We observed sex-related differences in the electrical remodeling of BB in AF patients. Women have a higher proportion of low voltage potentials, and more abnormal potential morphologies compared to men. These findings may reflect sex-specific differences in the underlying substrate of AF at BB.

Background: Prior studies demonstrated that female sex is associated with arrhythmia recurrence after endovascular pulmonary vein isolation (PVI). However, it is unknown if the sexes differ in outcome after video assisted thoracoscopic (VATS) PVI. The aim of this study was therefore to compare characteristics of recurrent AF episodes in a matched male and female population, using implantable loop recorders for continuous rhythm monitoring. Methods: 40 matched (based on propensity score) males (age: 60.0 ± 7.71 (45–75)) and females (age: 62.0 ± 7.0 (37–74)) were retrieved from an existing database from a prior conducted study by the cardiothoracic department of the OLVG hospital (1) containing patients who received an implantable looprecorder and underwent a VATS PVI between 2012 and 2017. Patients were continuously monitored for a period of 12 months after VATS PVI and AF characteristics were compared. Results: An equal number of males and females had AF episodes during all periods (P > 0.05). The number of AF episodes was higher in females, during the first 6 months (P = 0.01, P = 0.034). During the entire follow up, the total AF duration was longer in females (P = 0.01, for all periods) with shorter inter - episode intervals (P = 0.001, P = 0001, P = 0.04) and a higher AF burden (P = 0.003, P = 0001, P = 0.006). After 3 months, AF recurrences during the night were more frequently observed in female patients (P = 0.001, P = 0.001). Conclusions: AF episodes occur frequently in both sexes after VATS PVI and warrant frequent rhythm monitoring. The observed sex differences in AF burden after VATS PVI, calls for intensive rhythm monitoring and aggressive treatment of recurrent AF epsiodes in females.

Background The purpose of this study was to validate a technique for measuring mean calcium density and to determine associations of cardiovascular risk factors with carotid calcium density. Methods and Results We performed a cross-sectional study in a random sample of 100 stroke-free participants from the population-based Rotterdam Study. The mean calcium density of the combined left and right carotid bifurcations was quantified with a threshold of 130 Hounsfield Units (HU) using a novel density technique. To validate the methodology, carotid calcium volumes acquired using the technique in the current study were compared with measurements computed using dedicated clinical software (semiautomatic technique based on a threshold of ≥130 HU). Next, we investigated the associations of participant demographics, total calcium volume, and known cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, obesity, and smoking status) with the newly derived mean carotid calcium density measurement using linear regression analyses. Calcium volumes obtained with the 2 methods showed a high agreement (intraclass correlation coefficient=0.99, P<0.001), underlining the validity of the density technique. The total calcium volume was statistically significantly associated with the mean calcium density (cardiovascular risk factors adjusted model (B: 0.48 [95% CI, 0.30-0.66], P<0.001). We also found an association between hypercholesterolemia and mean calcium density (0.46 [0.09-0.83], P=0.017). No other significant associations were found between participant demographics or cardiovascular risk factors and mean carotid calcium density. Conclusions We demonstrated the feasibility of a carotid calcium density measurement technique. The data warrant a subsequent longitudinal study to determine the association between carotid calcium density and the risk of cerebrovascular events.

Background: Accumulating evidence highlights the existence of distinct morphological subtypes of intracranial carotid arteriosclerosis. So far, little is known on the prevalence of these subtypes and subsequent stroke risk in the general population. We determined the prevalence of morphological subtypes of intracranial arteriosclerosis and assessed the risk of stroke associated with these subtypes. Methods: Between 2003 and 2006, 2391 stroke-free participants (mean age 69.6, 51.7% women) from the population-based Rotterdam Study underwent noncontrast computed tomography to visualize calcification in the intracranial carotid arteries as a proxy for intracranial arteriosclerosis. Calcification morphology was evaluated according to a validated grading scale and categorized into intimal, internal elastic lamina (IEL), or mixed subtype. Follow-up for stroke was complete until January 1, 2016. We used multivariable Cox regression to assess associations of each subtype with incident stroke. Results: The prevalence of calcification was 82% of which 39% had the intimal subtype, 48% IEL subtype, and 13% a mixed subtype. During a median follow-up of 10.4 years, 155 participants had a stroke. All 3 subtypes were associated with a higher risk of stroke (adjusted hazard ratio [95% CI] for intimal: 2.11 [1.07-4.13], IEL: 2.66 [1.39-5.11], and mixed subtype 2.57 [1.18-5.61]). The association of the IEL subtype with stroke was strongest among older participants. The association of the intimal subtype with stroke was noticeably stronger in women than in men. Conclusions: Calcification of the IEL was the most prevalent subtype of intracranial arteriosclerosis. All 3 subtypes were associated with an increased risk of stroke, with noticeable age and sex-specific differences.

Despite a substantial genetic component, efforts to identify common genetic variation underlying depression have largely been unsuccessful. In the current study we aimed to identify rare genetic variants that might have large effects on depression in the general population. Using high-coverage exome-sequencing, we studied the exonic variants in 1265 individuals from the Rotterdam study (RS), who were assessed for depressive symptoms. We identified a missense Asn396Ser mutation (rs77960347) in the endothelial lipase (LIPG) gene, occurring with an allele frequency of 1% in the general population, which was significantly associated with depressive symptoms (P-value=5.2 × 10 -08, β=7.2). Replication in three independent data sets (N=3612) confirmed the association of Asn396Ser (P-value=7.1 × 10 -03, β=2.55) with depressive symptoms. LIPG is predicted to have enzymatic function in steroid biosynthesis, cholesterol biosynthesis and thyroid hormone metabolic processes. The Asn396Ser variant is predicted to have a damaging effect on the function of LIPG. Within the discovery population, carriers also showed an increased burden of white matter lesions (P-value=3.3 × 1 -02) and a higher risk of Alzheimer's disease (odds ration=2.01; P-value=2.8 × 10 -02) compared with the non-carriers. Together, these findings implicate the Asn396Ser variant of LIPG in the pathogenesis of depressive symptoms in the general population.