Economic analyses in cardiac electrophysiology: from clinical efficacy to cost utility.

Cardiac electrophysiology is an evolving field that relies heavily on costly device- and catheter-based technologies. An increasing number of patients with heart rhythm disorders are becoming eligible for cardiac interventions, not least due to the rising prevalence of atrial fibrillation and increased longevity in the population. Meanwhile, the expansive costs of healthcare face finite societal resources, and a cost-conscious approach to new technologies is critical. Cost-effectiveness analyses support rational decision-making in healthcare by evaluating the ratio of healthcare costs to health benefits for competing therapies. They may, however, be subject to significant uncertainty and bias. This paper aims to introduce the basic concepts, framework, and limitations of cost-effectiveness analyses to clinicians including recent examples from clinical electrophysiology and device therapy.

Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation: AXAFA biomolecule study.

AIMS: Different disease processes can combine to cause atrial fibrillation (AF). Their contribution to recurrent AF after ablation in patients is not known. Cardiovascular processes associated with recurrent AF after AF ablation were determined by quantifying biomolecules related to inflammation, metabolism, proliferation, fibrosis, shear stress, atrial pressure, and others in the AXAFA biomolecule study. METHODS AND RESULTS: Twelve circulating cardiovascular biomolecules (ANGPT2, BMP10, CA125, hsCRP, ESM1, FABP3, FGF23, GDF15, IGFBP7, IL6, NT-proBNP, and hsTnT) were quantified in plasma samples obtained prior to a first AF ablation using high-throughput, high-precision assays. Cox regression was used to identify biomolecules associated with recurrent AF during the first 3 months after AF ablation. In 433 patients (64 years [58, 70]; 33% women), baseline concentrations of ANGPT2, BMP10, hsCRP, FGF23, FABP3, GDF15, and NT-proBNP were elevated in patients with recurrent AF (120/433; 28%). After adjustment for 11 clinical features and randomized treatment, elevated NT-proBNP [hazard ratio (HR) 1.58, 95% confidence interval (1.29, 1.94)], ANGPT2 [HR 1.37, (1.12, 1.67)], and BMP10 [HR 1.24 (1.02, 1.51)] remained associated with recurrent AF. Concentrations of ANGPT2, BMP10, and NT-proBNP decreased in patients who remained arrhythmia free, but not in patients with recurrent AF, highlighting their connection to AF. The other eight biomarkers showed unchanged concentrations. CONCLUSION: Elevated concentrations of ANGPT2, BMP10, and NT-proBNP are associated with recurrent AF after a first AF ablation, suggesting that processes linked to disturbed cardiomyocyte metabolism, altered atrial shear stress, and increased load contribute to AF after AF ablation in patients.

Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.

AIMS: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). METHODS AND RESULTS: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. CONCLUSIONS: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF.

Influence of multimorbidity and socioeconomic position on long-term healthcare utilization and prognosis in patients after cardiac resynchronization therapy implantation.

Aims: We aimed to investigate the influence of socioeconomic position (SEP) and multimorbidity on cross-sectional healthcare utilization and prognosis in patients after cardiac resynchronization therapy (CRT) implantation. Methods and results: We included first-time CRT recipients with left ventricular ejection fraction ≤35% implanted between 2000 and 2017. Data on chronic conditions, use of healthcare services, and demographics were obtained from Danish national administrative and health registries. Healthcare utilization (in- and outpatient hospitalizations, activities in general practice) was compared by multimorbidity categories and SEP by using a negative binomial regression model. The association between SEP, multimorbidity, and prognostic outcomes was analysed using Cox proportional hazards regression. We followed 2007 patients (median age of 70 years), 79% were male, 75% were on early retirement or state pension, 37% were living alone, and 41% had low education level for a median of 5.2 [inter-quartile range: 2.2-7.3) years. In adjusted regression models, a higher number of chronic conditions were associated with increased healthcare utilization. Both cardiovascular and non-cardiovascular hospital contacts were increased. Patients with low SEP had a higher number of chronic conditions, but SEP had limited influence on healthcare utilization. Patients living alone and those with low educational level had a trend towards a higher risk of all-cause mortality [adjusted hazard ratio (aHR): 1.17, 95% confidence interval (CI) 1.03-1.33, and aHR 1.09, 95% CI 0.96-1.24). Conclusion: Multimorbidity increased the use of cross-sectional healthcare services, whereas low SEP had minor influence on the utilizations. Living alone and low educational level showed a trend towards a higher risk of mortality after CRT implantation.

Association between socioeconomic position and discontinuation of pharmacotherapy for heart failure after cardiac resynchronization therapy.

AIMS: Pharmacological therapy remains a cornerstone in heart failure (HF) treatment despite implantation of a cardiac resynchronization therapy (CRT) device. The aim of this study was to investigate the association between 1) drug discontinuation, and 2) long-term adherence to HF pharmacotherapy after CRT implantation and socioeconomic position and multimorbidity. METHODS AND RESULTS: We conducted a registry-based cohort study including all patients who underwent a first-time CRT implantation at Aarhus University Hospital from 2000-2017. HF pharmacotherapy included beta blockers (BBs), renin angiotensin system inhibitors (ACEI/ARB), and mineralocorticoid receptor antagonists (MRAs). Patients were identified using the Danish Pacemaker and ICD Registry, and information about medication and comorbidities was obtained through linkage to the Danish health registries. We identified 2,007 patients of whom 1,880 (94%) were eligible for inclusion. The cumulative incidence of drug discontinuation at 10 years was 6% (95% confidence interval [CI] 5-8%) for BB, 10% (95% CI 9-12%) for ACEI/ARB, and 24% (95% CI 20-27%) for MRAs. Living alone was associated with higher BB discontinuation rates (hazard ratio [HR] 1.83, 95%CI 1.20-2.79), whereas patients with multimorbidity were more likely to discontinue ACEI/ARB- (HR 1.92, 95%CI 1.33-2.80) and MRA therapy (HR 1.51, 95% CI 1.10-2.09). Income- and educational level did not influence drug discontinuation rates, and similar adherence patterns were observed across all strata of socioeconomic position and multimorbidity. CONCLUSION: In patients with CRTs, drug discontinuation rates were low, and adherence to HF pharmacotherapy was comparable regardless of socioeconomic position. Living alone and multimorbidity were associated with discontinuation of specific HF drugs.

Coronary Artery Disease Is A Stronger Predictor of All-Cause Mortality Than Left Ventricular Ejection Fraction Among Patients With Newly Diagnosed Heart Failure: Insights From the WDHR.

BACKGROUND: In patients with newly diagnosed heart failure (HF) and left ventricular ejection fraction (LVEF) <50%, little is known whether LVEF per se or presence of coronary artery disease (CAD) provides independent prognostic information on all-cause mortality. METHODS AND RESULTS: Using the WDHR (Western Denmark Heart Registry), we identified 3620 patients with newly diagnosed HF and LVEF 10% to 49% referred for first-time coronary angiography as part of general workup of HF. Patients were stratified by LVEF (10%-35% versus 36%-49%) and presence of CAD. We estimated 10-year all-cause mortality risk and calculated hazard ratios adjusted for relevant comorbidities and risk factors (aHRs). CAD was present in 1592 (44%) patients. Lower LVEF was associated with a relative 15% increased 10-year mortality: 37% for LVEF 36% to 49% versus 42% for LVEF 10% to 35% (aHR, 1.15 [95% CI, 0.99-1.34]). This result did not change when stratified into those with CAD (52% versus 56%; aHR, 1.11 [95% CI, 0.91-1.35]) and those without CAD (27% versus 33%; aHR, 1.24 [95% CI, 0.97-1.57]). In comparison, presence and extent of CAD were associated with a relative 43% increased 10-year mortality (CAD versus no CAD, 55.0% versus 31.5%; aHR, 1.43 [95% CI, 1.25-1.64]). Compared with a matched general population, excess mortality risk was higher for patients with HF and CAD (54.7% versus 26.3%; aHR, 2.10 [95% CI, 1.85-2.39]) versus those with HF and no CAD (31.4% versus 17.2%; aHR, 1.76 [95% CI, 1.52-2.02]). CONCLUSIONS: Among newly diagnosed patients with HF and LVEF <50%, presence and extent of CAD are associated with substantial higher all-cause mortality risk than lower LVEF.

Labor Market Participation Among Working-Age Heart Failure Patients With a Cardiac Resynchronization Therapy Device.

PURPOSE: Labor market participation is an important rehabilitation goal for working-age patients living with heart failure (HF). Cardiac resynchronization therapy (CRT) reduces mortality and HF hospitalizations and improves quality of life, but no studies have investigated labor market participation following CRT. We therefore aimed to describe labor market participation in patients with HF before and after CRT implantation. METHODS: This region-wide register-based cohort study comprised patients with HF aged 40 to 63 yr, with ejection fraction ≤35% and QRS duration >130 milliseconds, who received a CRT system from 2000 to 2017 in the Central Denmark Region. Using unambiguous, individual-level linkage in Danish medical and administrative registries, we assessed weekly employment status from 1 yr prior to CRT implantation until 2 to 5 yr of follow-up and conducted stratified analyses by sociodemographic and disease-related risk factors. RESULTS: We identified 546 patients, of whom 42% were in early retirement 1 yr prior to implantation. Active employment decreased from 45% to 19% from 1 yr before until implantation, declining primarily in the last 8 wk before implantation. The proportion of patients in active employment increased in the first 8 wk after CRT implantation and then stabilized, reaching 31% at 1-yr follow-up. We observed lower labor market participation in patients with older age, multimorbidity, lower educational level, and upgrade procedures, but higher in later calendar year. CONCLUSIONS: In working-age patients with HF, labor market participation increased after CRT implantation, despite many patients being retired prior to implantation. We observed differences in active employment related to several sociodemographic and disease-related factors.

Contractile asymmetry and survival in patients with left bundle branch abnormality treated with cardiac resynchronization therapy.

Aims: Currently, electrical rather than mechanical parameters of delayed left ventricular (LV) activation are used for patient selection for cardiac resynchronization therapy (CRT). However, despite adhering to current guideline-based criteria, about one-third of heart failure (HF) patients fail to derive benefit from CRT. This study sought to investigate the prognostic survival significance of a recently introduced index of contractile asymmetry (ICA) based on the deformation of entire opposing LV walls in the context of selecting patients with HF and left bundle branch abnormality (LBBB) for CRT. Methods and results: We analysed 367 patients with HF and LBBB undergoing CRT (31.6% females, 69 ± 9 years, ischaemic aetiology in 50.7%, LV ejection fraction 27 ± 6%). ICA was calculated using LV strain rate values from curved anatomical M-mode plots of apical 2D echocardiography images. The predictive value of ICA was assessed using Kaplan-Meier analysis and Cox proportional hazards models. During a median follow-up time of 5.54 years, death or cardiac transplantation occurred in 105 (28.6%) cases. Higher baseline ICA values in all apical views, particularly in the two-chamber view (ICA-2ch), were associated with increased event-free survival, and the unadjusted hazard ratio was 0.28 (95% confidence interval 0.18-0.46). Higher ICA-2ch (>0.319 s-1) consistently predicted survival across clinical subgroups and remained significant after covariate adjustment, while the event rate sharply increased in low ICA-2ch cases. Additionally, including ICA-2ch improved the predictive value of the multivariate risk model containing the typical LBBB pattern. Conclusion: Pre-implant ICA suggests a quantitative prognostic threshold for both long-term survival and adverse outcomes following CRT implantation.