Role of sex and gender-related variables in development of metabolic syndrome: A prospective cohort study.

INTRODUCTION: The burden of metabolic syndrome (MetS) and its components has been increasing mainly amongst male individuals. Nevertheless, clinical outcomes related to MetS (i.e., cardiovascular diseases), are worse among female individuals. Whether these sex differences in the components and sequalae of MetS are influenced by gender (i.e., psycho-socio-cultural factors)) is a matter of debate.  Therefore, the purpose of this study was to determine the association between gender-related factors and the development of MetS, and to assess if the magnitude of the associations vary by sex. METHOD: Data from the Colaus/PsyColaus study, a prospective population-based cohort of 6,734 middle-aged participants in Lausanne (Switzerland) (2003-2006) were used. The primary endpoint was the development of MetS as defined by the Adult Treatment Panel III of the National Cholesterol Education Program. Multivariable models were estimated using logistic regression to assess the association between gender-related factors and the development of MetS. Two-way interactions between sex,  age and gender-related factors were also tested. RESULTS: Among 5,195 participants without MetS (mean age=51.3 ± 10.6, 56.1 % females), 27.9 % developed MetS during a mean follow-up of 10.9 years. Female sex (OR:0.48, 95 %CI:0.41-0.55) was associated with decreased risk of developing MetS. Conversely, older age, educational attainment less than university, and low income were associated with an increased risk of developing MetS. Statistically significant interaction between sex and strata of age, education, income, smoking, and employment were identified showing that the reduced risk of MetS in female individuals was attenuated in the lowest education, income, and advanced age strata. However, females who smoke and reported being employed demonstrated a decreased risk of MetS compared to males. Conversely smoking and unemployment were significant risk factors for MetS development among male adults. CONCLUSIONS: Gender-related factors such as income level and educational attainment play a greater role in the development of MetS in female than individuals. These factors represent novel modifiable targets for implementation of sex- and gender-specific strategies to achieve health equity for all people.

Sex and gender aspects in diabetes mellitus: Focus on access to health care and cardiovascular outcomes.

Aims: The aim of this study was to elucidate whether sex and gender factors influence access to health care and/or are associated with cardiovascular (CV) outcomes of individuals with diabetes mellitus (DM) across different countries. Methods: Using data from the Canadian Community Health Survey (8.4% of respondent reporting DM) and the European Health Interview Survey (7.3% of respondents reporting DM), were analyzed. Self-reported sex and a composite measure of socio-cultural gender was constructed (range: 0-1; higher score represent participants who reported more characteristics traditionally ascribed to women). For the purposes of analyses the Gender Inequality Index (GII) was used as a country level measure of institutionalized gender. Results: Canadian females with DM were more likely to undergo HbA1c monitoring compared to males (OR = 1.26, 95% CI: 1.01-1.58), while conversely in the European cohort females with DM were less likely to have their blood sugar measured compared to males (OR = 0.88, 95% CI: 0.79-0.99). A higher gender score in both cohorts was associated with less frequent diabetes monitoring. Additionally, independent of sex, higher gender scores were associated with higher prevalence of self-reported heart disease, stroke, and hospitalization in all countries albeit European countries with medium-high GII, conferred a higher risk of all outcomes and hospitalization rates than low GII countries. Conclusion: Regardless of sex, individuals with DM who reported characteristics typically ascribed to women and those living in countries with greater gender inequity for women exhibited poorer diabetes care and greater risk of CV outcomes and hospitalizations.

The role of sex and gender in hypertension.

Hypertension (HTN) is a critical primary modifiable risk factor for the development of cardiovascular diseases, with recognized sex-based differences. While sex refers to one's biological genetic makeup and attributes, gender encompasses the individual's psycho-socio-cultural characteristics, including their environment and living conditions. The impact of each gendered variable may differ amongst men and women with respect to HTN. Applying a sex and gender-based lenses to inform our understanding of HTN has the potential to unveil important contributors of HTN-related cardiovascular outcomes. For instance, increased life stressors, work related anxiety and depression, typically have more pronounced effect on women than men with HTN. The impact of social surrounding including marital status and social support on HTN also differs amongst men and women. While married men are less likely to have higher blood pressure, single women, and those who never married are less likely to have HTN. Additionally, the beneficial role of social support is more pronounced in more historically marginalized cultural groups compared to majority. Finally, socioeconomic status, including education level and income have a linear and inverse relationship in blood pressure control in more resource-rich countries. The aim of this review is to summarize how sex and gender interact in shaping the clinical course of HTN demonstrating the importance of both sex and gender in HTN risk and its treatment. Hence, when investigating the role of gendered factors in HTN it is imperative to consider cultural, and social settings. In this narrative we found that employment and education play a significant role in manifestation and control of HTN particularly in women.

Importance of sex and gender factors for COVID-19 infection and hospitalisation: a sex-stratified analysis using machine learning in UK Biobank data.

OBJECTIVE: To examine sex and gender roles in COVID-19 test positivity and hospitalisation in sex-stratified predictive models using machine learning. DESIGN: Cross-sectional study. SETTING: UK Biobank prospective cohort. PARTICIPANTS: Participants tested between 16 March 2020 and 18 May 2020 were analysed. MAIN OUTCOME MEASURES: The endpoints of the study were COVID-19 test positivity and hospitalisation. Forty-two individuals' demographics, psychosocial factors and comorbidities were used as likely determinants of outcomes. Gradient boosting machine was used for building prediction models. RESULTS: Of 4510 individuals tested (51.2% female, mean age=68.5±8.9 years), 29.4% tested positive. Males were more likely to be positive than females (31.6% vs 27.3%, p=0.001). In females, living in more deprived areas, lower income, increased low-density lipoprotein (LDL) to high-density lipoprotein (HDL) ratio, working night shifts and living with a greater number of family members were associated with a higher likelihood of COVID-19 positive test. While in males, greater body mass index and LDL to HDL ratio were the factors associated with a positive test. Older age and adverse cardiometabolic characteristics were the most prominent variables associated with hospitalisation of test-positive patients in both overall and sex-stratified models. CONCLUSION: High-risk jobs, crowded living arrangements and living in deprived areas were associated with increased COVID-19 infection in females, while high-risk cardiometabolic characteristics were more influential in males. Gender-related factors have a greater impact on females; hence, they should be considered in identifying priority groups for COVID-19 infection vaccination campaigns.

Representation of Women in Atrial Fibrillation Clinical Practice Guidelines.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in men and women worldwide, and its prevalence is increasing. Management of AF is guided by evidence-based clinical practice guidelines which provide recommendations based on available evidence. The extent of sex-specific data in the AF literature used to provide guideline recommendations has not been investigated. Therefore, using the 2020 Canadian Cardiovascular Society (CCS) AF management guidelines as an example, the purpose of this study was to review female representation and the reporting of sex-disaggregated data in the studies referenced in AF guidelines. METHODS: Randomised controlled trials (RCTs) and prospective and retrospective cohorts were screened to calculate the proportion of study participants who were female and to establish whether studies provided sex-disaggregated analyses. The participant-prevalence ratio (PPR), a quotient of the female participant rate and the prevalence of women in the AF population, was calculated for each study. RESULTS: A total of 885 studies included in the CCS guidelines were considered. Of those, 467 met the inclusion criteria. Overall, women represented 39.1% of the population over all of the studies and RCTs had the lowest proportions of women (33.8%, PPR 0.70). Of studies with sex-disaggregated analyses (n = 140; 29.9%), single-centre RCTs and retrospective cohorts had the lowest and highest rates of sex-specific analyses, respectively (11.5% and 32.5%). CONCLUSIONS: The evidence used to derive guideline recommendations may be inadequate for sex-specific recommendations. Until enough data can support women-specific guidelines, increased inclusion of females in AF studies, may aid in the precision of recommendations.

Fluoroless Catheter Ablation of Atrial Fibrillation: Integration of Intracardiac Echocardiography and Cartosound Module.

OBJECTIVE: To evaluate the feasibility, safety, and clinical efficacy of non-fluoroscopic radiofrequency catheter ablation of atrial fibrillation (AF) in comparison to traditional fluoroscopy-guided ablation in a local Canadian community cohort. METHODS: We retrospectively studied consecutive patients with paroxysmal and persistent AF undergoing pulmonary vein isolation (PVI) guided by intracardiac echocardiography (ICE) and Carto system (CartoSound module). ICE-guided PVI without fluoroscopy (Zero-fluoro group) was performed in 116 patients, and conventional fluoroscopy-guided PVI (Traditional group) was performed in 131 patients. RESULTS: Two hundred and forty-seven patients with AF (60.7% male; mean age: 62.2 ± 10.6 years; paroxysmal AF =63.1%) who underwent PVI were studied. Mean procedure times were similar between both groups (136.8±33.4 minutes in the zero-fluoro group vs. 144.3±44.9 minutes in the traditional group; p=0.2). Acute PVI was achieved in all patients. Survival from early AF recurrence was 85% and 81% in the zero-fluoro and traditional groups, respectively (p = 0.06). Survival from late AF recurrence (12-months) between the zero-fluoro and traditional groups was also similar (p=0.1). Moreover, there were no significant differences between complication rates, including hematoma (p = 0.2) and tamponade (p = 1),between both groups. CONCLUSIONS: Zero-fluoroscopy ICE and CartoSound-guided AF ablation may be safe and feasible in patients undergoing PVI compared to conventional fluoroscopy-guided ablation.

Comparison of hospitalized patients with COVID-19 who did and did not live in residential care facilities in Montréal: a retrospective case series.

BACKGROUND: As in other jurisdictions, the demographics of people infected with SARS-CoV-2 changed in Quebec over the course of the first COVID-19 pandemic wave, and affected those living in residential care facilities (RCFs) disproportionately. We evaluated the association between clinical characteristics and outcomes of hospitalized patients with COVID-19, comparing those did or did not live in RCFs. METHODS: We conducted a retrospective case series of all consecutive adults (≥ 18 yr) admitted to the Jewish General Hospital in Montréal with laboratory-confirmed SARS-CoV-2 infection from Mar. 4 to June 30, 2020, with in-hospital follow-up until Aug. 6, 2020. We collected patient demographics, comorbidities and outcomes (i.e., admission to the intensive care unit, mechanical ventilation and death) from medical and laboratory records and compared patients who did or did not live in public and private RCFs. We evaluated factors associated with the risk of in-hospital death with a Cox proportional hazard model. RESULTS: In total, 656 patients were hospitalized between March and June 2020, including 303 patients who lived in RCFs and 353 patients who did not. The mean age was 72.9 (standard deviation 18.3) years (range 21 to 106 yr); 349 (53.2%) were female and 118 (18.0%) were admitted to the intensive care unit. The overall mortality rate was 23.8% (156/656), but was higher among patients living in RCFs (36.6% [111/303]) compared with those not living in RCFs (12.7% [45/353]). Increased risk of death was associated with age 80 years and older (hazard ratio [HR] 2.39, 95% confidence interval [CI] 1.35-4.24), male sex (HR 1.74, 95% CI 1.25-2.41), the presence of 4 or more comorbidities (HR 2.01, 95% CI 1.18-3.42) and living in an RCF (HR 1.62, 95% CI 1.09-2.39). INTERPRETATION: During the first wave of the COVID-19 epidemic in Montréal, more than one-third of RCF residents hospitalized with SARS-CoV-2 infection died during hospitalization. Policies and practices that prevent future outbreaks of SARS-CoV-2 infection in this setting must be implemented to prevent high mortality in this vulnerable population.

The Importance of Gender to Understand Sex Differences in Cardiovascular Disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. There is robust evidence of heterogeneity in underlying mechanism, manifestation, prognosis, and response to treatment of CVD between male and female patients. Gender, which refers to the socially constructed roles, behaviours, expressions, and identities of individuals, is an important determinant of CV health, and its consideration might help in attaining a broader understanding of the observed sex differences in CVD. Established risk factors such as hypertension, dyslipidemia, diabetes mellitus, obesity, and smoking are well known to contribute to CVD. However, despite the differences in CVD risk between male and female, most studies looking into the magnitude of effect of each risk factor have traditionally focused on male subjects. While biological sex influences disease pathophysiology, the psycho-socio-cultural construct of gender can further interact with this effect. Behavioural, psychosocial, personal, cultural, and societal factors can create, repress, or strengthen underlying biological CV health differences. Although mechanisms of action are largely unclear, it is suggested that gender-related factors can further exacerbate the detrimental effect of established risk factors of CVD. In this narrative review, we explore the current literature investigating the role of gender in CV risk and its impact on established risk factors as a fundamental step toward precision medicine.

Relationship between quality of life and burden of recurrent atrial fibrillation following ablation: CAPCOST multicentre cohort study.

AIMS: Atrial fibrillation (AF) significantly impairs patients' quality of life (QOL). We performed this study to investigate the effect of AF-ablation success and atrial fibrillation burden (AFB) on QOL measures. METHODS AND RESULTS: Overall, 230 patients with paroxysmal AF refractory to antiarrhythmic drugs were enrolled and underwent ablation in a multicentre, prospective cohort. Electrocardiogram, 48-h Holter, Canadian Cardiovascular Society Severity of Atrial Fibrillation (CCS-SAF), short form-12 (SF-12), and Atrial Fibrillation Effect on Quality of life (AFEQT) scales were used to assess patients. Atrial fibrillation burden was defined as total duration of AF during the month prior to each visit (h/month). The change in AFB was calculated as the difference between the month prior to the 12-month post-ablation and the baseline pre-ablation. The Minimal Clinically Important Difference (MCID) was considered as a 19-point change for AFEQT and 3-5-point change for SF-12 scores. There was significant rise in the AFEQT and SF12 and decrease in CCS-SAF score post-AF ablation; however, the magnitude of these changes was greater in patients without AF recurrence (P < 0.05). The QOL score that best differentiated patients with and without recurrence was AFEQT, while, CCS-SAF was the most specific score. Patients with AFB decrease >19 h/month had significantly greater change in QOL scores. Atrial fibrillation burden < 24 h/month at 12-months post-ablation was associated with significant changes in QOL and CCS-SAF when adjusting for baseline scores and other covariates. These changes were consistent with the MCID of these measures. CONCLUSION: Patients experience significant improvements in QOL post-ablation, which correlate with a decrease in AFB despite ongoing brief recurrences of AF. CLINICAL TRIAL REGISTRATION: NCT01562912. https://www.clinicaltrials.gov/ct2/show/NCT01562912? term=capcost&rank=1.

Pseudoaneurysm of thoracic aorta presenting as inappropriate sinus tachycardia: a case report.

BACKGROUND: Pseudoaneurysm of thoracic aorta as a complication of blunt trauma to the chest, can present with a variety of symptoms due to mass compression effect. Here we report the first pseudoaneurysm of thoracic aorta presenting with chronic cough and inappropriate sinus tachycardia. The purpose of this case report is to highlight pseudoaneurysm of thoracic aorta as a rare differential diagnosis for inappropriate sinus tachycardia. CASE PRESENTATION: Here we report a case of 29-year-old white woman, a nurse, with history of a motor vehicle accident. She initially presented to medical attention with inappropriate sinus tachycardia 2 years following the motor vehicle accident during her pregnancy. Six years later she underwent sinoatrial node modification after failing a number of medications. Days prior to the ablation she developed a mild cough which became constant within a week following ablation. A computed tomography scan of her chest performed as part of a workup revealed an outpouching of the inferomedial aspect of the aortic arch, which was compressing her left main bronchus. She underwent arch repair surgery and recovered without complications. Four years later she presented with significant symptomatic sinus bradycardia requiring pacemaker placement. CONCLUSIONS: This is the first reported case of thoracic pseudoaneurysm of aorta presenting with inappropriate sinus tachycardia due to compression of the vagal nerve and cough as a result of the left main bronchus compressive effect; it highlights the importance of considering structural abnormalities in a differential diagnosis of inappropriate sinus tachycardia before any interventions.

Comparison of efficacy of phased multipolar versus traditional radiofrequency ablation: A prospective, multicenter study (CAPCOST).

BACKGROUND: Multipolar phased pulmonary vein ablation catheter (PVAC), specifically its second-generation (PVAC-Gold), has been associated with reduced procedural time for atrial fibrillation (AF) ablation compared to traditional catheters. We performed this study to compare the efficacy of PVAC with point-by-point radiofrequency (RF) ablation. METHODS: This is a multicenter-cohort study (2012-2017), involving patients with symptomatic, paroxysmal AF refractory to at least one antiarrhythmic medication. Overall, 230 patients were enrolled to (A) PVAC and (B) control groups. Subanalyses were done for ablations performed with PVAC-Gold, and for ablations performed without left atrial (LA) ablation in addition to pulmonary vein isolation. Electrocardiogram and 48-h Holter monitoring were used to assess patients at 3, 6, 9, and 12 months postablation. Recurrence was defined as any atrial arrhythmia >30 s excluding an initial 3-month blanking period. RESULTS: Freedom from any atrial arrhythmia at 12 months postablation was 35.70% and 52.80% in groups A and B, respectively (P = .01). Freedom from atrial arrhythmia was not significantly different when limiting the PVAC cohort to PVAC-Gold and excluding patients with additional LA ablation (A: 44.30%; B: 44.30%, P = .80). Procedural and ablation time was significantly lower in group A than B. Multivariate regression model showed female gender (odds ratio [OR] = 2.90) and recurrence during blanking period (OR = 6.60) as significant predictors of recurrence. CONCLUSION: This study suggests that PVAC may achieve less freedom from AF than point-by-point RF; however, efficacy is similar when comparing PVAC-Gold and point-by-point stand-alone PV isolation. PVAC is associated with significantly reduced procedural times for AF ablation.

Defining Blanking Period Post-Pulmonary Vein Antrum Isolation.

OBJECTIVES: This study sought to determine the exact period after pulmonary vein antrum isolation (PVI) during which early recurrence of atrial tachyarrhythmia (ERAT) does not predict late arrhythmia recurrence (LR), in order to better define the blanking period. BACKGROUND: Recurrence of atrial fibrillation after PVI is not uncommon. The first 3 months after PVI have been commonly treated as a blanking period, during which ERAT is not thought to predict LR after PVI; however, recent studies have shown that ERAT does predict LR. METHODS: Baseline and follow-up data for 636 patients (mean age: 61.4 ± 10.6 years; 67.1% male; 59% paroxysmal atrial fibrillation; 31.4% ERAT) who underwent PVI between 2010 and 2014 were included. Recurrences were monitored by electrocardiography and Holter monitoring at 1-, 3-, 6-, 9-, and 12-month intervals post-procedure. Receiver-operating characteristic curve analysis was used to define the blanking period after PVI. RESULTS: Overall, 51%, 76%, and 92% of patients who had ERAT in the first, second, and third month post-PVI, respectively, also experienced LR (p = 0.001). Using a logistic regression model, those manifesting ERAT during the first, second, and third month post-PVI were 4.22, 9.03, and 19.43 (p = 0.001) times more likely to experience LR, respectively, compared to those without ERAT. Furthermore, receiver-operating characteristic analysis revealed that 23 days post-PVI is the optimal cutoff date for the blanking period, with area under the curve of 0.7, sensitivity of 69.2%, and specificity of 61.2%. CONCLUSIONS: The likelihood of experiencing LR progressively rises with ERAT after the first month post-PVI. Blanking period after PVI should be limited to the first 23 days clinically and in future studies.

Spatial Relationships of Complex Fractionated Atrial Electrograms and Continuous Electrical Activity to Focal Electrical Sources: Implications for Substrate Ablation in Human Atrial Fibrillation.

OBJECTIVES: This study sought to evaluate the spatial relationships of focal electrical sources (FSs) to complex fractionated atrial electrograms (CFAE) and continuous electrical activity (CEA). BACKGROUND: Fractionated atrial electrograms have been associated with atrial fibrillation (AF) drivers in computational studies and represent ablation targets in the management of persistent AF. METHODS: We included a subset of 66 patients (age: 63 [56, 67] years, 69% persistent AF) with electroanatomic data from the SELECT AF (Selective complex fractionated atrial electrograms targeting for atrial fibrillation) randomized control trial that compared the efficacy of CFAE with CEA ablation in AF patients undergoing pulmonary vein antral ablation. Focal sources were identified based on bipolar electrogram periodicity and QS unipolar electrogram morphology. RESULTS: A total of 77 FSs (median: 1 [1st quartile, 3rd quartile: 1, 2] per patient) were identified most commonly in the pulmonary vein antrum and left atrial appendage. The proportions of FSs inside CFAE and CEA regions were similar (13% vs. 1.3%, respectively; p = 0.13). Focal sources were more likely to be on the border zone of CFAEs than in CEAs (49% vs. 7.8%, respectively; p = 0.012). Following ablation, 53% of patients had ≥1 unablated extrapulmonary vein FS. The median number of unablated FS was higher in patients with AF recurrence post ablation than in patients without (median: 1 [0, 1] vs. 0 [0, 1], respectively; p = 0.026). CONCLUSIONS: One-half of the FSs detected during AF localized to the border of CFAE areas, whereas most of the FSs were found outside CEA areas. CFAE or CEA ablation leaves a number of FS unablated, which is associated with AF recurrence. These findings suggest that many CFAEs may arise from passive wave propagation, remote from FS, which may limit their therapeutic efficacy in AF substrate modification.

Risk of Stroke and Recurrence After AF Ablation in Patients With an Initial Event-Free Period of 12 Months.

INTRODUCTION: Because of the unclear prognostic effects of ablation of atrial fibrillation (AF), oral anticoagulation (OAC) is often continued after ablation even in asymptomatic patients. We sought to determine the frequency of stroke and AF recurrence in patients on and off therapeutic OAC 1 year after a successful AF ablation. METHODS AND RESULTS: Patients that underwent AF ablation and were free of AF 12 months after ablation were selected from our AF database. During follow-up (FU), patients were screened for recurrence of AF, changes in OAC or antiarrhythmic medication, and the occurrence of stroke or transient ischemic attack (TIA). A total of 398 patients (median age 60.7 years [50.8, 66.8], 25% female) were investigated. The median duration of FU was 529 (373, 111,3.5) days. OAC was discontinued in 276 patients (69.3%). During FU, 4 patients (1%) suffered from stroke and 55 patients (13.8%) experienced a recurrence of AF. Persistent AF was significantly associated with a greater chance of AF recurrence (49.1% vs. 26.8%; P = 0.001). Neither CHADS2 nor CHA2DS2-VASc-Score nor recurrence of AF were significantly different in patients with or without stroke. There was a trend toward a higher percentage of coronary artery disease among patients that experienced stroke (50% vs. 10%; P = 0.057). CONCLUSION: The overall risk of stroke and AF recurrence is low in patients with a recurrence free interval of at least 12 months after AF ablation. Of note, recurrence of AF was not associated with a higher risk of stroke in our study population.