Association between sodium-glucose cotransporter-2 inhibitors and arrhythmic outcomes in patients with diabetes and pre-existing atrial fibrillation.

AIMS: Prior studies suggest that sodium-glucose cotransporter-2 inhibitors (SGLT2is) may decrease the incidence of atrial fibrillation (AF). However, it is unknown whether SGLT2i can attenuate the disease course of AF among patients with pre-existing AF and Type II diabetes mellitus (DM). In this study, our objective was to examine the association between SGLT2i prescription and arrhythmic outcomes among patients with DM and pre-existing AF. METHODS AND RESULTS: We conducted a population-based cohort study of adults with DM and AF between 2014 and 2019. Using a prevalent new-user design, individuals prescribed SGLT2i were matched 1:1 to those prescribed dipeptidyl peptidase-4 inhibitors (DPP4is) based on time-conditional propensity scores. The primary endpoint was a composite of AF-related healthcare utilization (i.e. hospitalization, emergency department visits, electrical cardioversion, or catheter ablation). Secondary outcome measures included all-cause mortality, heart failure (HF) hospitalization, and ischaemic stroke or transient ischaemic attack (TIA). Cox proportional hazard models were used to examine the association of SGLT2i with the study endpoint. Among 2242 patients with DM and AF followed for an average of 3.0 years, the primary endpoint occurred in 8.7% (n = 97) of patients in the SGLT2i group vs. 10.0% (n = 112) of patients in the DPP4i group [adjusted hazard ratio 0.73 (95% confidence interval 0.55-0.96; P = 0.03)]. Sodium-glucose cotransporter-2 inhibitors were associated with significant reductions in all-cause mortality and HF hospitalization, but there was no difference in the risk of ischaemic stroke/TIA. CONCLUSION: Among patients with DM and pre-existing AF, SGLT2is are associated with decreased AF-related health resource utilization and improved arrhythmic outcomes compared with DPP4is.

Unsupervised item response theory models for assessing sample heterogeneity in patient-reported outcomes measures.

PURPOSE: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models. METHODS: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics. RESULTS: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease. CONCLUSION: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models' Type I error and statistical power for identifying covariates associated with DIF.

Response shift in coronary artery disease.

PURPOSE: Patients with coronary artery disease (CAD) experience significant angina symptoms and lifestyle changes. Revascularization procedures can result in better patient-reported outcomes (PROs) than optimal medical therapy (OMT) alone. This study evaluates the impact of response shift (RS) on changes in PROs of patients with CAD across treatment strategies. METHODS: Data were from patients with CAD in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease (APPROACH) registry who completed the 16-item Canadian version of the Seattle Angina Questionnaire at 2 weeks and 1 year following a coronary angiogram. Multi-group confirmatory factor analysis (MG-CFA) was used to assess measurement invariance across treatment groups at week 2. Longitudinal MG-CFA was used to test for RS according to receipt of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical therapy (OMT) alone. RESULTS: Of the 3116 patients included in the analysis, 443 (14.2%) received CABG, 2049(65.8%) PCI, and the remainder OMT alone. The MG-CFA revealed a partial-strong invariance across the treatment groups at 2 weeks (CFI = 0.98, RMSEA [90% CI] = 0.05 [0.03, 0.06]). Recalibration RS was detected on the Angina Symptoms and Burden subscale and its magnitude in the OMT, PCI, and CABG groups were 0.32, 0.28, and 0.53, respectively. After adjusting for RS effects, the estimated target changes were largest in the CABG group and negligible in the OMT group. CONCLUSION: Adjusting for RS is recommended in studies that use SAQ-CAN to assess changes in patients with CAD who have received revascularization versus OMT alone.

Left atrium 4D-flow segmentation with high-resolution contrast-enhanced magnetic resonance angiography.

Background: Atrial fibrillation (AF) leads to intracardiac thrombus and an associated risk of stroke. Phase-contrast cardiovascular magnetic resonance (CMR) with flow-encoding in all three spatial directions (4D-flow) provides a time-resolved 3D volume image with 3D blood velocity, which brings individual hemodynamic information affecting thrombus formation. As the resolution and contrast of 4D-flow are limited, we proposed a semi-automated 4D-flow segmentation method for the left atrium (LA) using a standard-of-care contrast-enhanced magnetic resonance angiography (CE-MRA) and registration technique. Methods: LA of 54 patients with AF were segmented from 4D-flow taken in sinus rhythm using two segmentation methods. (1) Phase-contrast magnetic resonance angiography (PC-MRA) was calculated from 4D-flow, and LA was segmented slice-by-slice manually. (2) LA and other structures were segmented from CE-MRA and transformed into 4D-flow coordinates by registration with the mutual information method. Overlap of volume was tested by the Dice similarity coefficient (DSC) and the average symmetric surface distance (ASSD). Mean velocity and stasis were calculated to compare the functional property of LA from two segmentation methods. Results: LA volumes from segmentation on CE-MRA were strongly correlated with PC-MRA volume, although mean CE-MRA volumes were about 10% larger. The proposed registration scheme resulted in visually successful registration in 76% of cases after two rounds of registration. The mean of DSC of the registered cases was 0.770 ± 0.045, and the mean of ASSD was 2.704 mm ± 0.668 mm. Mean velocity had no significant difference between the two segmentation methods, and mean stasis had a 3.3% difference. Conclusion: The proposed CE-MRA segmentation and registration method can generate segmentation for 4D-flow images. This method will facilitate 4D-flow analysis for AF patients by making segmentation easier and overcoming the limit of resolution.

Optimal medical therapy improves outcomes in patients with diabetes mellitus and acute myocardial infarction.

AIMS: We aimed to explored the association between the use of optimal medical therapy (OMT) in patients with myocardial infarction (AMI) and diabetes mellitus (DM) and clinical outcomes. METHODS: Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) is an international registry that enrolled participants with acute coronary syndrome followed up for at least 1 year across 15 centers from 2003 to 2014. Baseline characteristics and endpoints were analyzed. RESULTS: Among 3095 (23.2%) patients with AMI and DM, 1898 (61.3%) received OMT at hospital discharge. OMT was associated with significantly reduced mortality (4.3% vs. 10.8%, p < 0.001), re-AMI (4.4% vs. 8.1%, p < 0.001), and composite endpoint of death/re-AMI (8.0% vs. 17.6%, p < 0.001). No difference was observed among regions. Propensity score matching confirmed that OMT significantly associated with lower mortality. After adjusting for confounding variables, OMT, drug-eluting stents, and complete revascularization were independent protective factors of 1-year mortality, whereas left ventricular ejection fraction and age were risk factors. CONCLUSIONS: Guideline-recommended OMT was prescribed at suboptimal frequencies with geographic variations in this worldwide cohort. OMT can improve long-term clinical outcomes in patients with DM and AMI. CLINICAL TRIAL REGISTRATION: NCT02466854 June 9, 2015.

An evaluation of the role of the exercise training dose for changes in exercise capacity following a standard cardiac rehabilitation program.

BACKGROUND: To retrospectively characterize and compare the dose of exercise training (ET) within a large cohort of patients demonstrating different levels of improvement in exercise capacity following a cardiac rehabilitation (CR) program. METHODS: A total of 2310 patients who completed a 12-week, center-based, guidelines-informed CR program between January 2018 and December 2019 were included in the analysis. Peak metabolic equivalents (METpeak) were determined pre- and post-CR during which total duration (ET time) and intensity [percent of heart rate peak (%HRpeak)] of supervised ET were also obtained. Training responsiveness was quantified on the basis of changes in METpeak from pre- to post-CR. A cluster analysis was performed to identity clusters demonstrating discrete levels of responsiveness (i.e., negative, low, moderate, high, and very-high). These were compared for several baseline and ET-derived variables which were also included in a multivariable linear regression model. RESULTS: At pre-CR, baseline METpeak was progressively lower with greater training responsiveness (F(4,2305) = 44.2, P < 0.01, η2p = 0.71). Likewise, average training duration (F(4,2305) = 10.7 P < 0.01, η2p = 0.02) and %HRpeak (F(4,2305) = 25.1 P < 0.01, η2p = 0.042) quantified during onsite ET sessions were progressively greater with greater training responsiveness. The multivariable linear regression model confirmed that baseline METpeak, training duration and intensity during ET, BMI, and age (P < 0.001) were significant predictors of METpeak post-CR. CONCLUSIONS: Along with baseline METpeak, delta BMI, and age, the dose of ET (i.e., training duration and intensity) predicts METpeak at the conclusion of CR. A re-evaluation of current approaches for exercise intensity prescription is recommended to extend the benefits of completing CR to all patients.

Preferences of Patients With Chronic Kidney Disease for Invasive Versus Conservative Treatment of Acute Coronary Syndrome: A Discrete Choice Experiment.

Background Patients with chronic kidney disease (CKD) can experience acute coronary syndromes (ACS) with high morbidity and mortality. Early invasive management of ACS is recommended for most high-risk patients; however, choosing between an early invasive versus conservative management approach may be influenced by the unique risk of kidney failure for patients with CKD. Methods and Results This discrete choice experiment measured the preferences of patients with CKD for future cardiovascular events versus acute kidney injury and kidney failure following invasive heart procedures for ACS. The discrete choice experiment, consisting of 8 choice tasks, was administered to adult patients attending 2 CKD clinics in Calgary, Alberta. The part-worth utilities of each attribute were determined using multinomial logit models, and preference heterogeneity was explored using latent class analysis. A total of 140 patients completed the discrete choice experiment. The mean age of patients was 64 years, 52% were male, and mean estimated glomerular filtration rate was 37 mL/min per 1.73 m2. Across the range of levels, risk of mortality was the most important attribute, followed by risk of end-stage kidney disease and risk of recurrent myocardial infarction. Latent class analysis identified 2 distinct preference groups. The largest group included 115 (83%) patients, who placed the greatest value on treatment benefits and expressed the strongest preference for reducing mortality. A second group of 25 (17%) patients was identified who were procedure averse and had a strong preference toward conservative management of ACS and avoiding acute kidney injury requiring dialysis. Conclusions The preferences of most patients with CKD for management of ACS were most influenced by lowering mortality. However, a distinct subgroup of patients was strongly averse to invasive management. This highlights the importance of clarifying patient preferences to ensure treatment decisions are aligned with patient values.

Effect of Multifactorial Risk Factor Interventions on Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Evidence supports the benefit of managing atrial fibrillation (AF) specific risk factors in secondary prevention of AF. However, a comprehensive summary of the effect of multifactorial risk factor interventions on outcomes of patients with AF over long-term is lacking. We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL databases from inception to October 2021 for both randomized controlled trials (RCT) and observational studies comparing multifactorial risk factor interventions to usual care in patients with AF. Fifteen studies (10 RCT, 5 observational) with 3786 patients were included (mean age 63.8 years, 64.0% males). Follow-up ranged from 3 to 42 months. We found no significant effects of multifactorial risk factor interventions on AF recurrence [pooled relative risk (RR): 0.93, 95% CI: 0.74-1.16, P = 0.51, I2 = 54%], AF-related rehospitalization at 12 months (RR: 0.69, 95% CI: 0.43-1.11, P= 0.13, I2 = 0%), cardiovascular rehospitalization at 12 months (RR: 0.76, 95% CI: 0.53-1.09, P= 0.13, I2 = 53%), or AF-related adverse events at 12 and 15 months. However, multifactorial interventions were associated with reduced AF-related symptoms and improved health-related quality of life (HRQoL) at all studied time points. Current evidence does not support consistent associations between multifactorial risk factor interventions and AF recurrence after rhythm control therapy or AF-related or cardiovascular hospitalization in patients with AF. However, these interventions are associated with clinically relevant improvement in AF-related symptoms and HRQoL. Additional randomized studies are required to evaluate the impact of multifactorial risk factor interventions on patient-centered health outcomes.

Antithrombotic Strategy in Secondary Prevention for High-Risk Patients with Previous Acute Coronary Syndrome: Overlap between the PEGASUS Eligibility and the COMPASS Eligibility in a Large Multicenter Registry.

BACKGROUND: Patients with previous acute coronary syndrome (ACS) are at high risk of recurrent adverse cardiovascular events. Recently, prolonged dual antiplatelet therapy (DAPT) and oral anticoagulation therapy (OAT) have been shown to reduce recurrent ischemic events to the expense of an increase in bleeding events. The number of patients potentially eligible for these therapies in real life remains to be determined. METHODS: Among ACS patients from five registries and one randomized controlled trial, we assessed the proportion of patients eligible for the PEGASUS strategy only and the proportion of patients eligible for the COMPASS strategy only, and set out the proportion of patients with an overlap between the strategies. FINDINGS: Among the 10,048 evaluable patients, we found that 5373 (53.4%) were eligible for the PEGASUS strategy and 3841 (38.2%) were eligible for the COMPASS strategy, with a group of 3444 (34.4%) overlapping between the two strategies. The number of patients eligible for the PEGASUS strategy only was 1929 (19.2%) and the number eligible for the COMPASS strategy only was 397 (4.0%); 4278 (42.6%) were eligible for neither a PEGASUS strategy nor a COMPASS strategy. INTERPRETATION: In a large cohort of ACS patients, one in three patients was eligible for either a prolonged DAPT with ticagrelor 60 mg and low-dose aspirin or a dual pathway inhibition approach with rivaroxaban 2.5 mg and low-dose aspirin.

High-density mapping improves detection of conduction gaps after pulmonary vein isolation ablation with a circular mapping catheter.

BACKGROUND: High-density (HD) mapping of the pulmonary vein (PVs) has been hypothesized to improve the detection of conduction gaps in the radiofrequency ablation lesions set after pulmonary vein isolation (PVI) for the treatment of atrial fibrillation (AF). We aimed to compare the incidence of gaps after PVI with a standard 20-pole circumferential mapping catheter (CMC-20) and an HD mapping catheter (HD Grid). METHODS: This prospective study included patients scheduled for high-power short-duration PVI. Acute PVI was defined as an entrance and exit block using the CMC-20 after ≥ 20 min waiting period. The left atrium was then remapped using the HD Grid high-density mapping catheter to identify residual conduction gaps in the PVI lines by voltage and activation criteria. The primary endpoint was the number of gaps identified per patient by the HD Grid catheter. RESULTS: A total of 20 patients were included (mean age 59.9 ± 10.8 years, 15% female, 70% paroxysmal AF). The new map with the HD Grid identified 6 gaps in 4 patients (20%) or 0.3 ± 0.7 gaps per patient (p = 0.055 when compared to CMC-20). Five gaps (83%) were located at the right PVs. There was no difference in mapping time (CMC-20 12.2 ± 2.6 min vs HD Grid 11.7 ± 3.4 min, p = 0.452); however, the number of points was significantly higher in the HD Grid map (1662.7 ± 366.1 vs 1171.6 ± 313.6, p < 0.001). CONCLUSIONS: HD mapping during AF ablation identified PVI gaps in 1 out of 5 patients. Therefore, HD mapping may have the potential to improve AF ablation success rates in the long term. TRIAL REGISTRATION: ClinicalTrials.gov NCT04850508 on April 20, 2021.

Long-Term Maintenance of Cardiorespiratory Fitness Gains After Cardiac Rehabilitation Reduces Mortality Risk in Patients With Multimorbidity.

PURPOSE: The objective of this study was to characterize the impact of multimorbidity and cardiorespiratory fitness (CRF) on mortality in patients completing cardiac rehabilitation (CR). METHODS: This cohort study included data from patients with a history of cardiovascular disease (CVD) completing a 12-wk CR program between January 1996 and March 2016, with follow-up through March 2017. Patients were stratified by the presence of multimorbidity, which was defined as having a diagnosis of ≥2 noncommunicable diseases (NCDs). Cox regression analyses were used to evaluate the effects of multimorbidity and CRF on mortality in patients completing CR. Symptom-limited exercise tests were completed at baseline, immediately following CR (12 wk), with a subgroup completing another test at 1-yr follow-up. Peak metabolic equivalents (METs) were determined from treadmill speed and grade. RESULTS: Of the 8320 patients (61 ± 10 yr, 82% male) included in the analyses, 5713 (69%) patients only had CVD diagnosis, 2232 (27%) had CVD+1 NCD, and 375 (4%) had CVD+≥2 NCDs. Peak METs at baseline (7.8 ± 2.0, 6.9 ± 2.0, 6.1 ± 1.9 METs), change in peak METs immediately following CR (0.98 ± 0.98, 0.83 ± 0.95, 0.76 ± 0.95 METs), and change in peak METs 1 yr after CR (0.98 ± 1.27, 0.75 ± 1.17, 0.36 ± 1.24 METs) were different ( P < .001) among the subgroups. Peak METs at 12 wk and the presence of coexisting conditions were each predictors ( P < .001) of mortality. Improvements in CRF by ≥0.5 METS from baseline to 1-yr follow-up among patients with or without multimorbidity were associated with lower mortality rates. CONCLUSION: Increasing CRF by ≥0.5 METs improves survival regardless of multimorbidity status.

Cardiorespiratory fitness estimations and their ability to predict all-cause mortality in patients with cardiovascular disease.

Background: In cardiac rehabilitation programs, cardiorespiratory fitness is commonly estimated (eCRF) from the maximum workload achieved on a graded exercise test. This study compared four well-established eCRF equations in their ability to predict mortality in patients with cardiovascular disease (CVD). Methods: A total of 7269 individuals with CVD were studied (81% male; age 59.4 ± 10.3yr). eCRF was calculated using equations from the American College of Sports Medicine, Bruce et al., the Fitness Registry and the Importance of Exercise International Database, and McConnell and Clark. The eCRF from each equation was compared with a RMANOVA. Cox proportional hazard models assessed the relationship between the eCRF equations and mortality risk. The predictive ability of the models was compared using the concordance index. Results: There were 284 deaths (85% male) over a follow-up period of 5.8 ± 2.8yr. Although differences in eCRF were observed between each equation (P < 0.05), the eCRF from each of the four equations was predictive of mortality (P < 0.05). The concordance index values for each of the models were the same (0.77) indicating similar predictive performance. Conclusions: The four well-established eCRF equations did not differ in their ability to predict mortality in patients with CVD, indicating any could be used for this purpose. However, the differences in eCRF from each of the equations suggest potential differences in their ability to guide clinical care and should be the focus of future research.

Machine learning prediction of atrial fibrillation in cardiovascular patients using cardiac magnetic resonance and electronic health information.

Background: Atrial fibrillation (AF) is a commonly encountered cardiac arrhythmia associated with morbidity and substantial healthcare costs. While patients with cardiovascular disease experience the greatest risk of new-onset AF, no risk model has been developed to predict AF occurrence in this population. We hypothesized that a patient-specific model could be delivered using cardiovascular magnetic resonance (CMR) disease phenotyping, contextual patient health information, and machine learning. Methods: Nine thousand four hundred forty-eight patients referred for CMR imaging were enrolled and followed over a 5-year period. Seven thousand, six hundred thirty-nine had no prior history of AF and were eligible to train and validate machine learning algorithms. Random survival forests (RSFs) were used to predict new-onset AF and compared to Cox proportional-hazard (CPH) models. The best performing features were identified from 115 variables sourced from three data domains: (i) CMR-based disease phenotype, (ii) patient health questionnaire, and (iii) electronic health records. We evaluated discriminative performance of optimized models using C-index and time-dependent AUC (tAUC). Results: A RSF-based model of 20 variables (CIROC-AF-20) delivered an overall C-index of 0.78 for the prediction of new-onset AF with respective tAUCs of 0.80, 0.79, and 0.78 at 1-, 2- and 3-years. This outperformed a novel CPH-based model and historic AF risk scores. At 1-year of follow-up, validation cohort patients classified as high-risk of future AF by CIROC-AF-20 went on to experience a 17.3% incidence of new-onset AF, being 24.7-fold higher risk than low risk patients. Conclusions: Using phenotypic data available at time of CMR imaging we developed and validated the first described risk model for the prediction of new-onset AF in patients with cardiovascular disease. Complementary value was provided by variables from patient-reported measures of health and the electronic health record, illustrating the value of multi-domain phenotypic data for the prediction of AF.

Effect of Clinical Decision Support With Audit and Feedback on Prevention of Acute Kidney Injury in Patients Undergoing Coronary Angiography: A Randomized Clinical Trial.

Importance: Contrast-associated acute kidney injury (AKI) is a common complication of coronary angiography and percutaneous coronary intervention (PCI) that has been associated with high costs and adverse long-term outcomes. Objective: To determine whether a multifaceted intervention is effective for the prevention of AKI after coronary angiography or PCI. Design, Setting, and Participants: A stepped-wedge, cluster randomized clinical trial was conducted in Alberta, Canada, that included all invasive cardiologists at 3 cardiac catheterization laboratories who were randomized to various start dates for the intervention between January 2018 and September 2019. Eligible patients were aged 18 years or older who underwent nonemergency coronary angiography, PCI, or both; who were not undergoing dialysis; and who had a predicted AKI risk of greater than 5%. Thirty-four physicians performed 7820 procedures among 7106 patients who met the inclusion criteria. Participant follow-up ended in November 2020. Interventions: During the intervention period, cardiologists received educational outreach, computerized clinical decision support on contrast volume and hemodynamic-guided intravenous fluid targets, and audit and feedback. During the control (preintervention) period, cardiologists provided usual care and did not receive the intervention. Main Outcomes and Measures: The primary outcome was AKI. There were 12 secondary outcomes, including contrast volume, intravenous fluid administration, and major adverse cardiovascular and kidney events. The analyses were conducted using time-adjusted models. Results: Of the 34 participating cardiologists who were divided into 8 clusters by practice group and center, the intervention group included 31 who performed 4327 procedures among 4032 patients (mean age, 70.3 [SD, 10.7] years; 1384 were women [32.0%]) and the control group included 34 who performed 3493 procedures among 3251 patients (mean age, 70.2 [SD, 10.8] years; 1151 were women [33.0%]). The incidence of AKI was 7.2% (310 events after 4327 procedures) during the intervention period and 8.6% (299 events after 3493 procedures) during the control period (between-group difference, -2.3% [95% CI, -0.6% to -4.1%]; odds ratio [OR], 0.72 [95% CI, 0.56 to 0.93]; P = .01). Of 12 prespecified secondary outcomes, 8 showed no significant difference. The proportion of procedures in which excessive contrast volumes were used was reduced to 38.1% during the intervention period from 51.7% during the control period (between-group difference, -12.0% [95% CI, -14.4% to -9.4%]; OR, 0.77 [95% CI, 0.65 to 0.90]; P = .002). The proportion of procedures in eligible patients in whom insufficient intravenous fluid was given was reduced to 60.8% during the intervention period from 75.1% during the control period (between-group difference, -15.8% [95% CI, -19.7% to -12.0%]; OR, 0.68 [95% CI, 0.53 to 0.87]; P = .002). There were no significant between-group differences in major adverse cardiovascular events or major adverse kidney events. Conclusions and Relevance: Among cardiologists randomized to an intervention including clinical decision support with audit and feedback, patients undergoing coronary procedures during the intervention period were less likely to develop AKI compared with those treated during the control period, with a time-adjusted absolute risk reduction of 2.3%. Whether this intervention would show efficacy outside this study setting requires further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT03453996.

Influence of Sex-Based Differences in Cardiac Phenotype on Atrial Fibrillation Recurrence in Patients Undergoing Pulmonary Vein Isolation.

Background: Pulmonary vein isolation (PVI) is a commonly engaged therapy for symptomatic atrial fibrillation (AF). Prior studies have documented elevated AF recurrence rates among females vs. males. Sex-specific mechanisms underlying this phenomenon are poorly understood. This prospective cohort study aimed to evaluate the sex-based differences in cardiac phenotype and their influence on (AF) recurrence following first-time PVI. Methods: A total of 204 consecutive patients referred for first-time PVI and 101 healthy subjects were prospectively studied by cardiovascular magnetic resonance (CMR) imaging. Multi-chamber volumetric and functional measures were assessed by sex-corrected Z-score analyses vs. healthy subjects. Patients were followed for a median of 2.6 years for the primary outcome of clinical AF recurrence. Multivariable analyses adjusting for age and comorbidities were performed to identify independent predictors of AF recurrence. Results: AF recurrence following first PVI occurred in 41% of males and 59% of females (p = 0.03). Females were older with higher prevalence of hypertension and thyroid disorders. Z-score-based analyses revealed significantly reduced ventricular volumes, greater left atrial (LA) volumes, and reduced LA contractility in females vs. males. Multivariable analysis revealed each of LA minimum and pre-systolic volumes and booster EF Z-scores to be independently associated with AF recurrence, providing respective hazard ratios of 1.10, 1.19, and 0.89 (p = 0.001, 0.03, and 0.01). Conclusion: Among patients referred for first time PVI, females were older and demonstrated significantly poorer LA contractile health vs. males, the latter independently associated with AF recurrence. Assessment of LA contractile health may therefore be of value to identify female patients at elevated risk of AF recurrence. Factors influencing female patient referral for PVI at more advanced stages of atrial disease warrant focused investigation.

Geographic and temporal variation in the treatment and outcomes of atrial fibrillation: a population-based analysis of national quality indicators.

BACKGROUND: Assessment of potential geographic variation in quality indicators of atrial fibrillation care may identify opportunities for improvement in the quality of atrial fibrillation care. The objective of this study was to assess for potential geographic variation in the quality of atrial fibrillation care in Alberta, Canada. METHODS: In a population-based cohort of adults (age ≥ 18 yr) with incident nonvalvular atrial fibrillation (NVAF) diagnosed between Apr. 1, 2008, and Mar. 31, 2016, in Alberta, we investigated the variation in national quality indicators of atrial fibrillation care developed by the Canadian Cardiovascular Society. Specifically, we assessed the geographic and temporal variation in the proportion of patients with initiation of oral anticoagulant therapy, persistence with therapy, ischemic stroke and major bleeding outcomes 1 year after atrial fibrillation diagnosis using linked administrative data sets. We defined stroke risk using the CHADS2 score. We assessed geographic variation using small-area variation statistics and geospatial data analysis. RESULTS: Of the 64 093 patients in the study cohort (35 019 men [54.6%] and 29 074 women [45.4%] with a mean age of 69 [standard deviation 15.9] yr), 36 199 were at high risk for stroke and 14 411 were at moderate risk. Within 1 year of NVAF diagnosis, 20 180 patients (55.7%) in the high-risk group and 6448 patients (44.7%) in the moderate-risk group were prescribed anticoagulation. A total of 2187 patients (3.4%) had an ischemic stroke, and 2996 patients (4.7%) experienced a major bleed. There was substantial regional variation observed in initiation of oral anticoagulant therapy but not in the proportion of patients with ischemic stroke or major bleeding. Among the 64 Health Status Areas in Alberta, therapy initiation rates ranged from 22.6% to 71.2% among patients at high stroke risk and from 22.7% to 55.8% among those at moderate stroke risk, with clustering of lower therapy initiation rates in rural northern regions. INTERPRETATION: The rate of initiation of oral anticoagulant therapy among adults with incident atrial fibrillation was less than 60% in patients in whom oral anticoagulant therapy would be considered guideline-appropriate care. The large geographic variation in oral anticoagulant prescribing warrants additional study into patient, provider and health care system factors that contribute to variation and drive disparities in high-quality, equitable atrial fibrillation care.

Cardiac Rehabilitation and Risk of Incident Atrial Fibrillation in Patients With Coronary Artery Disease.

BACKGROUND: Patients with coronary artery disease (CAD) are at risk for developing atrial fibrillation (AF). Whether attending a cardiac rehabilitation (CR) program can attenuate this risk is unclear. METHODS: This retrospective cohort study included patients who were free of pre-existing AF and referred to CR after coronary revascularization between April 2004 and March 2015 in Calgary, Canada. Patients with incident AF were identified using administrative data and the local electrocardiogram repository. Exposure variables and covariates were extracted from electronic medical records of a CR program and a clinical registry. RESULTS: The study included 11,662 patients (mean age [standard deviation], 60.9 [10.9] years; male, 80.6%). In a median follow-up of 4.8 years, the cumulative incidence rate of AF was 1.04 per 100 person-years. There was no association between completion of CR and the risk of incident AF after adjusting for baseline characteristics (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.83-1.15). However, each higher metabolic equivalent (MET) of baseline cardiorespiratory fitness (CRF) and each MET gain in CRF following CR were independently associated with a 12% (95% CI, 6%-18%) and 18% (95% CI, 6%-28%) lower relative risk of incident AF, respectively. The risk of incident AF declined progressively, with the baseline CRF increasing up to 9.0 peak METs and with the 12-week CRF increasing up to 10.3 peak METs; beyond these peak MET levels, benefits plateaued. CONCLUSIONS: Completion of CR alone was not associated with a lower risk of incident AF. However, higher baseline CRF and greater CRF improvement had dose-dependent protective effects.

Health State Utility Values in People With Stroke: A Systematic Review and Meta-Analysis.

Background Health state utility values are commonly used to provide summary measures of health-related quality of life in studies of stroke. Contemporaneous summaries are needed as a benchmark to contextualize future observational studies and inform the effectiveness of interventions aimed at improving post-stroke quality of life. Methods and Results We conducted a systematic search of the literature using Medline, EMBASE, and Web of Science from January 1995 until October 2020 using search terms for stroke, health-related quality of life, and indirect health utility metrics. We calculated pooled estimates of health utility values for EQ-5D-3L, EQ-5D-5L, AQoL, HUI2, HUI3, 15D, and SF-6D using random effects models. For the EQ-5D-3L we conducted stratified meta-analyses and meta-regression by key subgroups. We screened 14 251 abstracts and 111 studies met our inclusion criteria (sample size range 11 to 12 447). EQ-5D-3L was reported in 78% of studies (study n=87; patient n=56 976). The pooled estimate for EQ-5D-3L at ≥3 months following stroke was 0.65 (95% CI, 0.63-0.67), which was ≈20% below population norms. There was high heterogeneity (I2>90%) between studies, and estimates differed by study size, case definition of stroke, and country of study. Women, older individuals, those with hemorrhagic stroke, and patients prior to discharge had lower pooled EQ-5D-3L estimates. Conclusions Pooled estimates of health utility for stroke survivors were substantially below population averages. We provide reference values for health utility in stroke to support future clinical and economic studies and identify subgroups with lower healthy utility. Registration URL: https://www.crd.york.ac.uk/prospero/. Unique Identifier: CRD42020215942.

Heart rate variability as a function of menopausal status, menstrual cycle phase, and estradiol level.

Low estradiol status is associated with increased cardiovascular risk. We sought to determine the association between heart rate variability (HRV), a marker of cardiovascular risk, at baseline and in response to stressor as a function of menopausal status, menstrual cycle phase and estradiol level. Forty-one healthy women (13 postmenopausal, 28 premenopausal) were studied. Eleven premenopausal women were additionally studied in the high and low estradiol phases of the menstrual cycle. HRV was calculated by spectral power analysis (low Frequency (LF), high frequency (HF) and LF:HF) at baseline and in response to graded Angiotensin II (AngII) infusion. The primary outcomes were differences in HRV at baseline and in response to AngII. Compared to premenopausal women in the low estradiol phase, postmenopausal women demonstrated lower baseline LF (p = 0.01) and HF (p < 0.001) measures, which were not significant after adjustment for age and BMI. In response to AngII, a decrease in cardioprotective HRV (ΔHF = -0.43 ± 0.46 ln ms2 , p = 0.005 vs. baseline) was observed in postmenopausal women versus premenopausal women. Baseline HRV parameters did not differ by menstrual phase in premenopausal women. During the low estradiol phase, no differences were observed in the HRV response to AngII challenge. In contrast, women in the high estradiol phase were unable to maintain HRV (ΔLF = -0.07 ± 0.46 ln ms2 , p = 0.048 response vs. baseline, ΔHF = -0.33 ± 0.74 ln ms2, p = 0.048 response vs. baseline). No association was observed between any measure of HRV and estradiol level. Menopausal status and the high estradiol phase in premenopausal women were associated with reduced HRV, a marker of cardiovascular risk. Understanding the role of estradiol in the modulation of cardiac autonomic tone may help guide risk reduction strategies in women.

Prediction of Mortality in Coronary Artery Disease: Role of Machine Learning and Maximal Exercise Capacity.

OBJECTIVE: To develop a prediction model for survival of patients with coronary artery disease (CAD) using health conditions beyond cardiovascular risk factors, including maximal exercise capacity, through the application of machine learning (ML) techniques. METHODS: Analysis of data from a retrospective cohort linking clinical, administrative, and vital status databases from 1995 to 2016 was performed. Inclusion criteria were age 18 years or older, diagnosis of CAD, referral to a cardiac rehabilitation program, and available baseline exercise test results. Primary outcome was death from any cause. Feature selection was performed using supervised and unsupervised ML techniques. The final prognostic model used the survival tree (ST) algorithm. RESULTS: From the cohort of 13,362 patients (60±11 years; 2400 [18%] women), 1577 died during a median follow-up of 8 years (interquartile range, 4 to 13 years), with an estimated survival of 67% up to 21 years. Feature selection revealed age and peak metabolic equivalents (METs) as the features with the greatest importance for mortality prediction. Using these 2 features, the ST generated a long-term prediction with a C-index of 0.729 by splitting patients in 8 clusters with different survival probabilities (P<.001). The ST root node was split by peak METs of 6.15 or less or more than 6.15, and each patient's subgroup was further split by age or other peak METs cut points. CONCLUSION: Applying ML techniques, age and maximal exercise capacity accurately predict mortality in patients with CAD and outperform variables commonly used for decision-making in clinical practice. A novel and simple prognostic model was established, and maximal exercise capacity was further suggested to be one of the most powerful predictors of mortality in CAD.