A randomized controlled trial of a "Small Changes" behavioral weight loss treatment delivered in cardiac rehabilitation for patients with atrial fibrillation and obesity: study protocol for the BE-WEL in CR-AF study.

BACKGROUND: Atrial fibrillation (AF) represents a global epidemic. Although international AF practice guidelines indicate weight loss for patients with AF and comorbid obesity (BMI ≥ 30 kg/m2) to alleviate symptom burden and improve prognosis, few cardiac rehabilitation (CR) programs include targeted weight loss treatment. AIMS: This RCT protocol will evaluate the efficacy of a "Small Changes" behavioral weight loss treatment (BWLT) to produce clinically relevant (≥ 10%) weight loss among patients with AF and obesity undergoing CR, relative to CR alone. Secondary aims are to establish efficacy of CR + BWLT for improving AF symptoms, AF risk factors, and health-related quality of life. METHODS: Adults (18 +) with AF and obesity will be recruited and randomized to receive CR + BWLT (intervention) or CR-only (control). Controls will receive CR consisting of supervised exercise and risk factor self-management for 12 weeks. The intervention group will receive CR plus BWLT (12 weekly, group-based virtual sessions, followed by 12 weeks of follow-up support). Weight and AF-risk factors will be assessed at pre-randomization, 12 weeks, 24 weeks, and 52 weeks. AF burden will be assessed using 30-s ECGs recorded bidaily and with AF symptoms. The primary endpoint of weight loss will be calculated from baseline to 52 weeks as a percentage of starting weight. Intention-to-treat analyses will compare the proportion in each group achieving ≥ 10% weight loss. Assuming success rates of 5% and 30% among controls and intervention groups, respectively, and a 30% loss to follow-up, 120 patients (60 per group) will provide 80% power to detect a difference using a two-sided independent test of proportions (alpha = 5%). IMPACT: This clinical trial will be the first to demonstrate that adding BWLT to CR promotes clinically meaningful weight loss among patients with AF and comorbid obesity. Findings will inform design and execution of a large efficacy trial of long-term (e.g., 5-year) clinical endpoints (e.g., AF severity, mortality). Implementing weight control interventions designed to target the AF substrate in CR could dramatically reduce morbidity and enhance quality of life among patients living with AF in Canada. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT05600829. Registered October 31, 2022.

Hospital and Physician Variability in Revascularization Decisions and Outcomes for Patients With 3-Vessel and Left Main Coronary Artery Disease: A Population-Based Cohort Study.

BACKGROUND: Hospital- and physician-level variation for selection of percutaneous coronary intervention versus coronary artery bypass grafting (CABG) for patients with coronary artery disease has been associated with outcome differences. However, most studies excluded patients treated medically. METHODS AND RESULTS: From 2010 to 2019, adults with 3-vessel or left main coronary artery disease at 3 hospitals (A, B, C) in Alberta, Canada, were categorized by treatment with medical therapy, percutaneous coronary intervention, or CABG. Multilevel regression models determined the proportion of variation in treatment attributable to patient, physician, and hospital factors, and survival models assessed outcomes including death and major adverse cardiovascular events over 5 years. Of 22 580 patients (mean age, 67 years; 80% men): 6677 (29%) received medical management, 9171 (41%) percutaneous coronary intervention, and 6732 (30%) CABG. Hospital factors accounted for 10.8% of treatment variation. In adjusted models (site A as reference), patients at sites B and C had 49% (95% CI, 44%-53%) and 43% (95% CI, 37%-49%) lower rates of medical therapy, respectively, and 31% (95% CI, 24%-38%) and 32% (95% CI, 24%-40%) lower rates of CABG. During 5.0 years median follow-up, 3287 (14.6%) patients died, with no intersite mortality differences. There were no between-site differences in acute coronary syndromes or stroke; patients at sites B and C had 24% lower risk (95% CI, 13%-34% and 11%-35%, respectively) of heart failure hospitalization. CONCLUSIONS: Hospital-level variation in selection of percutaneous coronary intervention, CABG, or medical therapy for patients with complex coronary artery disease was not associated with differences in 5-year mortality rates. Research and quality improvement initiatives comparing revascularization practices should include medically managed patients.

APPROACH e-PROM system: a user-centered development and evaluation of an electronic patient-reported outcomes measurement system for management of coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) confers increased risks of premature mortality, non-fatal morbidity, and significant impairment in functional status and health-related quality of life. Routine administration of electronic patient-reported outcome measures (PROMs) and its real time delivery to care providers is known to have the potential to inform routine cardiac care and to improve quality of care and patient outcomes. This study describes a user-centered development and evaluation of the Alberta Provincial Project for Outcomes Assessment (APPROACH) electronic Patient Reported Outcomes Measurement (e-PROM) system. This e-PROM system is an electronic system for the administration of PROMs to patients with CAD and the delivery of the summarized information to their care providers to facilitate patient-physician communication and shared decision-making. This electronic platform was designed to be accessible via web-based and hand-held devices. Heuristic and user acceptance evaluation were conducted with patients and attending care providers. RESULTS: The APPROACH e-PROM system was co-developed with patients and care providers, research investigators, informaticians and information technology experts. Five PROMs were selected for inclusion in the online platform after consultations with patient partners, care providers, and PROMs experts: the Seattle Angina Questionnaire, Patient Health Questionnaire, EuroQOL, and Medical Outcomes Study Social Support Survey, and Self-Care of Coronary Heart Disease Inventory. The heuristic evaluation was completed by four design experts who examined the usability of the prototype interfaces. User acceptance testing was completed with 13 patients and 10 cardiologists who evaluated prototype user interfaces of the e-PROM system. CONCLUSION: Both patients and physicians found the APPROACH e-PROM system to be easy to use, understandable, and acceptable. The APPROACH e-PROM system provides a user-informed electronic platform designed to incorporate PROMs into the delivery of individualized cardiac care for persons with CAD.

Assessing agreement between population-level administrative pharmaceutical databases and patient-reported medication dispensation in cardiac rehabilitation patients.

BACKGROUND: Pharmacoepidemiology has emerged as a crucial field in evaluating the use and effects of medications in large populations to ensure their safe and effective use. This study aimed to assess the agreement of cardiac medication use between a provincial medication database, the Pharmaceutical Information Network (PIN), and reconciled medication data from confirmation through patient interviews for patients referred to cardiac rehabilitation. METHODS: The study included data from patients referred to the TotalCardiology Rehabilitation CR program, and medication data was available in both TotalCardiology Rehabilitation charts and PIN. The accuracy of medication data obtained from patient interviews was compared to that obtained from PIN with proportions and kappa statistics to evaluate the reliability of PIN data in assessing medication use. RESULTS: Patient-reported usage was higher for statins (41.6 %) vs. 38.4 %), ACE/ARB, beta-blockers (75.7 %) vs. 73.7 %), DOAC (3.5 %) vs. 2.6 %), and ADP-receptor antagonists (71.0 %) vs. 68.1 %) than if PIN was used. Patient-reported usage data was lower for Ezetimibe (4.7 vs. 4.8 %), Aldosterone antagonists (5.4 %) vs. 5.5 %), digoxin (0.9 %) vs. 1.0 %), calcium channel blockers (19.2 vs. 19.9 %) and warfarin (7.2 %) vs. 8.1 %). The results indicated that the differences between the two sources were very small, with an average agreement of 95.3 % and a kappa of 0.70. CONCLUSION: The study's results, which show a high level of agreement between PIN and patient self-reporting, affirm the reliability of PIN data as a source for obtaining an accurate assessment of medication use. This finding is crucial in the context of pharmacoepidemiology research, where the accuracy of data is paramount. Further research to explore the complementary use of both data sources will be valuable.

External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Cardioversion is a rhythm control strategy to restore normal/sinus rhythm, and can be achieved through drugs (pharmacological) or a synchronised electric shock (electrical cardioversion). OBJECTIVES: To assess the efficacy and safety of pharmacological and electrical cardioversion for atrial fibrillation (AF), atrial flutter and atrial tachycardias. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) and three trials registers (ClinicalTrials.gov, WHO ICTRP and ISRCTN) on 14 February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) at the individual patient level. Patient populations were aged ≥ 18 years with AF of any type and duration, atrial flutter or other sustained related atrial arrhythmias, not occurring as a result of reversible causes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology to collect data and performed a network meta-analysis using the standard frequentist graph-theoretical approach using the netmeta package in R. We used GRADE to assess the quality of the evidence which we presented in our summary of findings with a judgement on certainty. We calculated differences using risk ratios (RR) and 95% confidence intervals (CI) as well as ranking treatments using a P value. We assessed clinical and statistical heterogeneity and split the networks for the primary outcome and acute procedural success, due to concerns about violating the transitivity assumption. MAIN RESULTS: We included 112 RCTs (139 records), from which we pooled data from 15,968 patients. The average age ranged from 47 to 72 years and the proportion of male patients ranged from 38% to 92%. Seventy-nine trials were considered to be at high risk of bias for at least one domain, 32 had no high risk of bias domains, but had at least one domain classified as uncertain risk, and one study was considered at low risk for all domains. For paroxysmal AF (35 trials), when compared to placebo, anteroapical (AA)/anteroposterior (AP) biphasic truncated exponential waveform (BTE) cardioversion (RR: 2.42; 95% CI 1.65 to 3.56), quinidine (RR: 2.23; 95% CI 1.49 to 3.34), ibutilide (RR: 2.00; 95% CI 1.28 to 3.12), propafenone (RR: 1.98; 95% CI 1.67 to 2.34), amiodarone (RR: 1.69; 95% CI 1.42 to 2.02), sotalol (RR: 1.58; 95% CI 1.08 to 2.31) and procainamide (RR: 1.49; 95% CI 1.13 to 1.97) likely result in a large increase in maintenance of sinus rhythm until hospital discharge or end of study follow-up (certainty of evidence: moderate). The effect size was larger for AA/AP incremental and was progressively smaller for the subsequent interventions. Despite low certainty of evidence, antazoline may result in a large increase (RR: 28.60; 95% CI 1.77 to 461.30) in this outcome. Similarly, low-certainty evidence suggests a large increase in this outcome for flecainide (RR: 2.17; 95% CI 1.68 to 2.79), vernakalant (RR: 2.13; 95% CI 1.52 to 2.99), and magnesium (RR: 1.73; 95% CI 0.79 to 3.79). For persistent AF (26 trials), one network was created for electrical cardioversion and showed that, when compared to AP BTE incremental energy with patches, AP BTE maximum energy with patches (RR 1.35, 95% CI 1.17 to 1.55) likely results in a large increase, and active compression AP BTE incremental energy with patches (RR: 1.14, 95% CI 1.00 to 1.131) likely results in an increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: high). Use of AP BTE incremental with paddles (RR: 1.03, 95% CI 0.98 to 1.09; certainty of evidence: low) may lead to a slight increase, and AP MDS Incremental paddles (RR: 0.95, 95% CI 0.86 to 1.05; certainty of evidence: low) may lead to a slight decrease in efficacy. On the other hand, AP MDS incremental energy using patches (RR: 0.78, 95% CI 0.70 to 0.87), AA RBW incremental energy with patches (RR: 0.76, 95% CI 0.66 to 0.88), AP RBW incremental energy with patches (RR: 0.76, 95% CI 0.68 to 0.86), AA MDS incremental energy with patches (RR: 0.76, 95% CI 0.67 to 0.86) and AA MDS incremental energy with paddles (RR: 0.68, 95% CI 0.53 to 0.83) probably result in a decrease in this outcome when compared to AP BTE incremental energy with patches (certainty of evidence: moderate). The network for pharmacological cardioversion showed that bepridil (RR: 2.29, 95% CI 1.26 to 4.17) and quindine (RR: 1.53, (95% CI 1.01 to 2.32) probably result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up when compared to amiodarone (certainty of evidence: moderate). Dofetilide (RR: 0.79, 95% CI 0.56 to 1.44), sotalol (RR: 0.89, 95% CI 0.67 to 1.18), propafenone (RR: 0.79, 95% CI 0.50 to 1.25) and pilsicainide (RR: 0.39, 95% CI 0.02 to 7.01) may result in a reduction in this outcome when compared to amiodarone, but the certainty of evidence is low. For atrial flutter (14 trials), a network could be created only for antiarrhythmic drugs. Using placebo as the common comparator, ibutilide (RR: 21.45, 95% CI 4.41 to 104.37), propafenone (RR: 7.15, 95% CI 1.27 to 40.10), dofetilide (RR: 6.43, 95% CI 1.38 to 29.91), and sotalol (RR: 6.39, 95% CI 1.03 to 39.78) probably result in a large increase in the maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: moderate), and procainamide (RR: 4.29, 95% CI 0.63 to 29.03), flecainide (RR 3.57, 95% CI 0.24 to 52.30) and vernakalant (RR: 1.18, 95% CI 0.05 to 27.37) may result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: low). All tested electrical cardioversion strategies for atrial flutter had very high efficacy (97.9% to 100%). The rate of mortality (14 deaths) and stroke or systemic embolism (3 events) at 30 days was extremely low. Data on quality of life were scarce and of uncertain clinical significance. No information was available regarding heart failure readmissions. Data on duration of hospitalisation was scarce, of low quality, and could not be pooled. AUTHORS' CONCLUSIONS: Despite the low quality of evidence, this systematic review provides important information on electrical and pharmacological strategies to help patients and physicians deal with AF and atrial flutter. In the assessment of the patient comorbidity profile, antiarrhythmic drug onset of action and side effect profile versus the need for a physician with experience in sedation, or anaesthetics support for electrical cardioversion are key aspects when choosing the cardioversion method.

Mortality Benefits of Cardiac Rehabilitation in Coronary Artery Disease Are Mediated by Comprehensive Risk Factor Modification: A Retrospective Cohort Study.

BACKGROUND: Cardiac rehabilitation (CR) is a multicomponent intervention to reduce adverse outcomes from coronary artery disease, but its mechanisms are not fully understood. The aims of this study were to examine the impact of CR on survival and cardiovascular risk factors, and to determine potential mediators between CR attendance and reduced mortality. METHODS AND RESULTS: A retrospective mediation analysis was conducted among 11 196 patients referred to a 12-week CR program following an acute coronary syndrome event between 2009 and 2019. A panel of cardiovascular risk factors was assessed at a CR intake visit and repeated on CR completion. All-cause and cardiovascular mortality were ascertained via health care administrative data sets at mean 4.2-year follow-up (SD, 2.81 years). CR completion was associated with reduced all-cause (adjusted hazard ratio [HR], 0.67 [95% CI, 0.54-0.83]) and cardiovascular (adjusted HR, 0.57 [95% CI, 0.40-0.81]) mortality, as well as improved cardiorespiratory fitness, lipid profile, body composition, psychological distress, and smoking rates (P<0.001). CR attendance had an indirect effect on all-cause mortality via improved cardiorespiratory fitness (ab=-0.006 [95% CI, -0.008 to -0.003]) and via low-density lipoprotein cholesterol (ab=-0.002 [95% CI, -0.003 to -0.0003]) and had an indirect effect on cardiovascular mortality via cardiorespiratory fitness (ab=-0.007 [95% CI, -0.012 to -0.003]). CONCLUSIONS: Cardiorespiratory fitness and lipid control partly explain the mortality benefits of CR and represent important secondary prevention targets.

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.

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.

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.

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.