Efficacy and Safety of Intravenous Diltiazem Versus Metoprolol in the Management of Atrial Fibrillation with Rapid Ventricular Response in the Emergency Department: A Comprehensive Umbrella Review of Systematic Reviews and Meta-analyses.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States, affecting 2.7-6.1 million people. AF can cause symptoms, but when it triggers a rapid ventricular response (RVR), most patients suffer from decompensation. Therefore, we performed an umbrella review of systematic reviews and meta-analyses comparing intravenous (IV) metoprolol and diltiazem to identify discrepancies, fill in knowledge gaps, and develop standardized decision-making guidelines for physicians to manage AF with RVR. A comprehensive search was conducted in PubMed, the Cochrane Library, and Scopus to identify studies for this umbrella review. The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation method, while the quality of the included reviews was evaluated using AMSTAR 2, the Cochrane Collaboration tool, and the Newcastle-Ottawa scale. This study comprehensively analyzed four meta-analyses covering 11 randomized controlled trials and 19 observational studies. The analysis showed that IV diltiazem treatment was significantly more successful in rate control for AF with rapid ventricular response (RVR) than IV metoprolol (risk ratio [RR], 1.30; 95% confidence interval [CI], 1.09-1.56; I 2 = 0%; P = .003). IV diltiazem also led to a significantly greater reduction in ventricular rate (mean difference, -14.55; 95% CI, -16.93 to -12.16; I 2 = 72%; P < .00001), particularly at 10 min. The analysis also revealed a significantly increased risk of hypotension associated with treatment with IV diltiazem (RR, 1.43; 95% CI, 1.14-1.79; I 2 = 0%; P = .002). In conclusion, IV diltiazem therapy achieved better rate control and ventricular rate decrease than metoprolol therapy in AF with RVR. Future clinical trials should compare calcium channel blockers and ß-blockers for heart rate control efficacy and safety, considering adverse events.

Atrial Fibrillation in Hypertrophic Cardiomyopathy.

Atrial fibrillation (AF) is common among patients with hypertrophic cardiomyopathy (HCM) with a prevalence greater than 25%. AF in HCM is associated with a high risk of stroke and can be a marker of more advanced cardiomyopathy. Although, it frequently results in cardiac hemodynamic changes which are poorly tolerated, it can be subclinical. Thus, prompt diagnosis and adequate management of AF are essential to minimizing AF-related adverse outcomes in HCM. All HCM patients should be screened for AF regularly, and those with high-risk features should be screened more frequently preferably with extended ambulatory monitoring. Once AF is detected, oral anticoagulation should be initiated. Both general and HCM-specific modifiable risk factors should be addressed and assessment for cardiomyopathy progression should be performed. Although no randomized controlled studies have compared rate versus rhythm control in HCM, early rhythm control could be considered to prevent further LA remodeling.

Renal Outcomes of Rhythm Control in Patients Recently Diagnosed With Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with impaired renal function and chronic kidney disease (CKD). OBJECTIVES: This study assessed the effects of rhythm control on renal function compared with rate control among patients recently diagnosed with AF. METHODS: A total of 20,886 patients with AF and available baseline estimated glomerular filtration rate (eGFR) data undergoing rhythm control (antiarrhythmic drugs or ablation) or rate control therapy, initiated within 1 year of AF diagnosis in 2005 to 2015, were identified from the Korean National Health Insurance Service database. The composite outcome of ≥30% decline in eGFR, acute kidney injury, kidney failure, or death from renal or cardiovascular causes was compared with the use of propensity overlap weighting between rhythm or rate control strategies in patients with or without significant CKD (eGFR <60 mL/min/1.73 m2). RESULTS: Of the included patients (median age 62 years, 32.7% female), 2,213 (10.6%) had eGFR <60 mL/min/1.73 m2. Among patients with significant CKD, early rhythm control, compared with rate control, was associated with a lower risk of the primary composite outcome (weighted incidence rate: 2.77 vs 3.92 per 100 person-years; weighted HR: 0.70; 95% CI: 0.52-0.95). In patients without significant CKD, there was no difference in the risk of the primary composite outcome between rhythm and rate control groups (weighted incidence rate: 3.41 vs 3.21 per 100 person-years; weighted HR: 1.06; 95% CI: 0.96-1.18). No differences in safety outcomes were found between rhythm and rate control strategies in patients without or with significant CKD. CONCLUSIONS: Among patients with AF and CKD, early rhythm control was associated with lower risks of adverse renal outcomes than rate control was.

Testing for a treatment effect in a selected subgroup.

There is a growing interest in clinical trials that investigate how patients may respond differently to an experimental treatment depending on the basis of some biomarker measured on a continuous scale, and in particular to identify some threshold value for the biomarker above which a positive treatment effect can be considered to have been demonstrated. This can be statistically challenging when the same data are used both to select the threshold and to test the treatment effect in the subpopulation that it defines. This paper describes a hierarchical testing framework to give familywise type I error rate control in this setting and proposes two specific tests that can be used within this framework. One, a simple test based on the estimated value from a linear regression model with treatment by biomarker interaction, is powerful but can lead to type I error rate inflation if the assumptions of the linear model are not met. The other is more robust to these assumptions, but can be slightly less powerful when the assumptions hold.

[Atrial fibrillation in combination with severe mitral regurgitation : Which should be treated first, the atrial fibrillation or the mitral valve?] / Vorhofflimmern bei gleichzeitig höhergradiger Mitralklappeninsuffizienz : Erst das Vorhofflimmern oder die Mitralklappe therapieren?

BACKGROUND: The primary therapeutic approach for severe secondary mitral regurgitation (MR) in combination with atrial fibrillation is often not clear. OBJECTIVES/METHODS: To create a therapeutic guideline for daily clinical practice based on a case report as well as basic literature. RESULTS: If a functional component is suspected, restoration of sinus rhythm may lead to a significant improvement in MR. The extent of the improvement and the time required to achieve this improvement are often difficult to predict. CONCLUSIONS: The involvement of an electrophysiologist is recommended in order to assess the likelihood of successful long-term rhythm control aimed at improving MR. In unclear cases, cardioversion combined with short-term administration of antiarrhythmic medication may be useful to demonstrate potential improvement of MR in sinus rhythm.

Landiolol for heart rate control in patients with septic shock and persistent tachycardia. A multicenter randomized clinical trial (Landi-SEP).

PURPOSE: Excessive tachycardia in resuscitated septic shock patients can impair hemodynamics and worsen patient outcome. We investigated whether heart rate (HR) control can be achieved without increased vasopressor requirements using the titratable highly selective, ultra-short-acting ß1-blocker landiolol. METHODS: This randomized, open-label, controlled trial was conducted at 20 sites in 7 European countries from 2018 to 2022 and investigated the efficacy and safety of landiolol in adult patients with septic shock and persistent tachycardia. Patients were randomly assigned to receive either landiolol along with standard treatment (n = 99) or standard treatment alone (n = 101). The combined primary endpoint was HR response (i.e., HR within the range of 80-94 beats per minute) and its maintenance without increasing vasopressor requirements during the first 24 h after treatment start. Key secondary endpoints were 28-day mortality and adverse events. RESULTS: Out of 196 included septic shock patients, 98 received standard treatment combined with landiolol and 98 standard treatment alone. A significantly larger proportion of patients met the combined primary endpoint in the landiolol group than in the control group (39.8% [39/98] vs. 23.5% [23/98]), with a between-group difference of 16.5% (95% confidence interval [CI]: 3.4-28.8%; p = 0.013). There were no statistically significant differences between study groups in tested secondary outcomes and adverse events. CONCLUSION: The ultra-short-acting beta-blocker landiolol was effective in reducing and maintaining HR without increasing vasopressor requirements after 24 h in patients with septic shock and persistent tachycardia. There were no differences in adverse events and clinical outcomes such as 28-day mortality vs. standard of care. The results of this study, in the context of previous trials, do not support a treatment strategy of stringent HR reduction (< 95 bpm) in an unselected septic shock population with persistent tachycardia. Further investigations are needed to identify septic shock patient phenotypes that benefit clinically from HR control.

Implementation of an atrial fibrillation better care (ABC) pathway management strategy: Findings from the Iranian registry of atrial fibrillation.

Introduction: The Atrial Fibrillation Better Care (ABC) pathway is such an integrated care approach, recommended in guidelines. The aim of this service evaluation study was to evaluate the impact of implementing the ABC pathway in Iranian population. Methods: In this prospective longitudinal cohort study, consecutive patients with a diagnosis of AF were initially evaluated. Patients at baseline were evaluated in hence of adherence to ABC pathway strategy. After study enrolment, first and second follow-up service evaluations were conducted at 6 and 12 months, respectively. Results: The use of vitamin K antagonists (VKA) decreased from 25.1 % at enrolment to 13.8 % at follow-up; instead, non-VKA oral anticoagulants (NOAC) utilization increased from 40.0 % to 86.1 %, while antiplatelet treatment decreased from 34.9 % to 0 %. Use of antihypertensive drugs, ARBs, diuretics, and statins increased after implementation of the ABC pathway. Implementation of the ABC pathway approach led to a decrease in the occurrence of stroke/TIA (from 6.3 % to 2.2 %, p = 0.002), systemic thromboembolism (from 1.4 % to 0.0 %, p = 0.04), nose bleeds (from 0.8 % to 0.6 %, p = 0.04), skin bruising (from 1.2 % to 0.0 %, p = 0.002), and heart failure (from 7.7 % to 4.7 %, p = 0.04). The proportion of patients in EHRA Class I-II increased from 93.3 % at enrolment to 98.1 % at follow-up. Conclusion: In this first study from a Middle East population, compliance with ABC pathway strategy in the management of AF was associated with optimization of management and general improvements in patient outcomes during follow-up.

Feedback control of heart rate during robotics-assisted tilt table exercise in patients after stroke: a clinical feasibility study.

BACKGROUND: Patients with neurological disorders including stroke use rehabilitation to improve cognitive abilities, to regain motor function and to reduce the risk of further complications. Robotics-assisted tilt table technology has been developed to provide early mobilisation and to automate therapy involving the lower limbs. The aim of this study was to evaluate the feasibility of employing a feedback control system for heart rate (HR) during robotics-assisted tilt table exercise in patients after a stroke. METHODS: This feasibility study was designed as a case series with 12 patients ( n = 12 ) with no restriction on the time post-stroke or on the degree of post-stroke impairment severity. A robotics-assisted tilt table was augmented with force sensors, a work rate estimation algorithm, and a biofeedback screen that facilitated volitional control of a target work rate. Dynamic models of HR response to changes in target work rate were estimated in system identification tests; nominal models were used to calculate the parameters of feedback controllers designed to give a specified closed-loop bandwidth; and the accuracy of HR control was assessed quantitatively in feedback control tests. RESULTS: Feedback control tests were successfully conducted in all 12 patients. Dynamic models of heart rate response to imposed work rate were estimated with a mean root-mean-square (RMS) model error of 2.16 beats per minute (bpm), while highly accurate feedback control of heart rate was achieved with a mean RMS tracking error (RMSE) of 2.00 bpm. Control accuracy, i.e. RMSE, was found to be strongly correlated with the magnitude of heart rate variability (HRV): patients with a low magnitude of HRV had low RMSE, i.e. more accurate HR control performance, and vice versa. CONCLUSIONS: Feedback control of heart rate during robotics-assisted tilt table exercise was found to be feasible. Future work should investigate robustness aspects of the feedback control system. Modifications to the exercise modality, or alternative modalities, should be explored that allow higher levels of work rate and heart rate intensity to be achieved.

One-year outcomes of rate versus rhythm control of atrial fibrillation in the Kerala-AF Registry.

Background: There is ongoing debate around rate versus rhythm control strategies for managing atrial fibrillation (AF), however, much of the data comes from Western cohorts. Kerala-AF represents the largest prospective AF cohort study from the Indian subcontinent. Objectives: To compare 12-month outcomes between rate and rhythm control strategies. Methods: Patients aged ≥18 years with non-transient AF were recruited from 53 hospitals across Kerala. Patients were stratified by rate or rhythm control. The primary outcome was a composite of all-cause mortality, arterial thromboembolism, acute coronary syndrome or hospitalization due to heart failure or arrhythmia at 12 months. Secondary outcomes included bleeding events and individual components of the primary. Predictors of the composite outcome were analysed by logistic regression. Results: A total of 2901 patients (mean age 64.6 years, 51% female) were included (2464 rate control, 437 rhythm control). Rates of the primary composite outcome did not differ between groups (29.7% vs 30.0%; p = .955), nor did any component of the primary. Bleeding outcomes were also similar (1.6% vs 1.9%; p = .848). Independent predictors of the primary composite outcome were older age (aOR 1.01; p = .013), BMI <18 (aOR 1.51; p = .025), permanent AF (aOR 0.78; p = .010), HFpEF (aOR 1.40; p = .023), HFrEF (aOR 1.39; p = .004), chronic kidney disease (aOR 1.36; p < .001), and prior thromboembolism (aOR 1.31; p = .014). Conclusion: In the Kerala-AF registry, 12-month outcomes did not differ between rate and rhythm control cohorts.

Rate control or rhythm control in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention.

Background: Restoring and maintaining sinus rhythm in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) has been studied in clinical trials to reduce symptoms and improve quality of life. Limited data exist on the effectiveness of rate or rhythm control therapy in these patients. Methods: Consecutive patients with AF and ACS or referred for PCI were prospectively recruited in Fuwai Hospital during 2017-2020. The primary endpoints were all-cause death and major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular mortality, myocardial infarction, ischemic stroke, non-central nervous system embolism and ischemia-driven revascularization. Kaplan-Meier curves and Cox regressions were performed to evaluate the association between rhythm/rate control and subsequent outcomes. For the primary endpoints, we used the Benjamini-Hochberg correction for multiple comparisons. Results: A total of 1499 patients with AF and ACS or undergoing PCI were included, with a median follow-up of 34.7 months. Compared to non-rate control, rate control strategy reduced the risk of subsequent MACCEs (adjusted HR, 0.320; 95 % CI 0.220-0.466; p <0.001; *p <0.002) and all-cause death (adjusted HR, 0.148; 95 % CI 0.093-0.236; p <0.001; *p <0.002). Similar trends were observed across all predefined subgroups (p <0.001). In the final multivariate model, rhythm control was not associated with a lower subsequent MACCEs but significantly improved all-cause mortality compared to non-rhythm control (adjusted HR, 0.546; 95 % CI 0.313-0.951; p =0.033; *p =0.044). Conclusions: In this real-world study, rate control strategy was associated with lower risk of MACCEs and all-cause death in AF and ACS or undergoing PCI. Besides, management with rhythm control strategy may improve all-cause mortality.

A Systematic Review of Ongoing Registered Research Studies on Post-Operative Atrial Fibrillation after Cardiac Surgery.

Background/Objectives: New-onset atrial fibrillation (AF) after cardiac surgery is associated with patient-important outcomes. Uncertainty persists regarding its prevention, detection, and management. This review seeks to identify, compile, and describe ongoing registered research studies involving patients with or at risk for post-operative AF (POAF) after cardiac surgery. Methods: We searched clinical trial registries in January 2023 for studies focusing on POAF prediction, prevention, detection, or management. We extracted data from each record and performed descriptive analyses. Results: In total, 121 studies met the eligibility criteria, including 82 randomized trials. Prevention studies are the most common (n = 77, 63.6%), followed by prediction (n = 21, 17.4%), management (n = 16, 13.2%), and detection studies (n = 7, 5.8%). POAF after cardiac surgery is an area of active research. Conclusions: There are many ongoing randomized prevention studies. However, two major clinical gaps persist; future randomized trials should compare rate and rhythm control in patients who develop POAF, and long-term follow-up studies should investigate strategies to monitor for AF recurrence in patients with POAF.

Comparative safety and efficacy of a hybrid intravenous and oral diltiazem protocol for acute rate control in the emergency department.

STUDY OBJECTIVE: Intravenous diltiazem has experienced numerous supply shortages over the past few years. The purpose of this study was to compare the safety and efficacy of a traditional diltiazem intravenous bolus and continuous infusion protocol to a diltiazem intravenous bolus and oral maintenance protocol for acute rate control in the emergency department. METHODS: Patients who received intravenous diltiazem in the emergency department between January 1, 2018 and May 31, 2019 were screened. Patients were included if they received the diltiazem intravenous bolus and continuous infusion protocol (IV + infusion group) or the hybrid diltiazem intravenous bolus and oral maintenance protocol (IV + PO group). The primary outcome was the proportion of patients with rate control, without need for additional rate control agents or additional boluses during the maintenance phase. RESULTS: A total of 106 patients were matched with 53 patients in each group. For the primary outcome of rate control at four hours, 62.3% of patients in the intravenous bolus + infusion group versus 75.5% of patients in the IV bolus + PO group (p = 0.142) achieved rate control. There was no difference in rates of hypotension or bradycardia between groups. CONCLUSION: Results of this study demonstrated no difference in acute rate control when using a hybrid IV and oral diltiazem protocol, compared to a traditional IV bolus and infusion strategy. This information supports the further use of a hybrid diltiazem IV and oral protocol, which provides increased flexibility during shortages of either medication.

Outcome of tailored therapy in rheumatic heart disease with persistent atrial fibrillation (RHD-AF).

INTRODUCTION: Rheumatic heart disease with persistent atrial fibrillation (RHD-AF) is associated with increased morbidity. However, there is no standardized approach for the maintenance of sinus rhythm (SR) in them. We aimed to determine the utility of a stepwise approach to achieve SR in RHD-AF. METHODS: Consecutive patients with RHD-AF from July 2021 to August 2023 formed the study cohort. The stepwise approach included pharmacological rhythm control and/or electrical cardioversion (Central illustration). In patients with recurrence, additional options included AF ablation or pace and ablate strategy with conduction system pacing or biventricular pacing. Clinical improvement, NT-proBNP, 6-Minute Walk Test (6MWT), heart failure (HF) hospitalizations, and thromboembolic complications were documented during follow-up. RESULTS: Eighty-three patients with RHD-AF (mean age 56.13 ± 9.51 years, women 72.28%) were included. Utilizing this approach, 43 (51.81%) achieved and maintained SR during the study period of 11.04 ± 7.14 months. These patients had improved functional class, lower NT-proBNP, better distance covered for 6MWT, and reduced HF hospitalizations. The duration of AF was shorter in patients who achieved SR, compared to those who remained in AF (3.15 ± 1.29 vs 6.93 ± 5.23, p = 0.041). Thirty-five percent (29) maintained SR after a single cardioversion over the study period. Only one underwent AF ablation. Of the 24 who underwent pace and ablate strategy, atrial lead was implanted in 22 (hybrid approach), and 50% of these achieved and maintained SR. Among these 24, none had HF hospitalizations, but patients who maintained SR had further improvement in clinical and functional parameters. CONCLUSIONS: RHD-AF patients who could achieve SR with a stepwise approach, had better clinical outcomes and lower HF hospitalizations.

Real-world evidence of early rhythm control in patients with atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: The favorable benefits of early rhythm control (ERC) therapy in newly diagnosed patients with atrial fibrillation (AF) have been demonstrated in the EAST-AFNET 4 trial. However, the generalizability and applicability of ERC in real-world clinical settings remain inconclusive. METHODS: We conducted a systematic search of the PubMed and Embase databases to identify observational studies published between January 2020 and February 2024 that focused on real-world evidence pertaining to ERC. The effectiveness and safety outcomes in our study were analogous to those evaluated in the EAST-AFNET 4 trial. RESULTS: A total of 4 observational studies that fulfilled the inclusion criteria of EAST-AFNET 4 were included, involving 130,970 patients with AF, 30.7% of whom received ERC therapy. In our pooled analysis using the fixed-effects model, compared with rate control, ERC significantly decreased the occurrence risk of the primary composite outcome (hazard ratio [HR] 0.86, 95% confidence interval[CI] 0.82-0.91), cardiovascular death (HR 0.87, 95% CI 0.78-0.98), stroke (HR 0.80, 95% CI 0.73-0.87), and hospitalization with worsening heart failure (HR 0.91, 95% CI 0.84-0.99) or acute coronary syndrome (HR 0.72, 95% CI 0.59-0.87). In terms of safety outcomes, there were no differences in the composite safety outcome (HR 1.00, 95% CI 0.95-1.05) and all-cause death (HR 0.93, 95% CI 0.82-1.06) between the two studied groups. CONCLUSIONS: ERC therapy showed favorable effectiveness outcomes compared with rate control, whereas the safety outcomes between the two therapeutic strategies did not differ significantly, supporting the benefits of ERC therapy over rate control in selected real-world patients with AF. REGISTRATION: The study protocol was registered to PROSPERO (CRD42023443569).

How to properly evaluate cardiac vagal tone in oncology studies: a state-of-the-art review.

Heart rate variability (HRV) analysis provides an assessment of cardiac vagal tone and consequently global cardiac health as well as systemic condition. In systemic diseases such as cancer and during treatments that affect the whole body, like chemotherapy, the vagus nerve activity is low and deregulated. Some studies focus on using HRV to predict mortality in oncology. However, in cancer patients, systemic alterations substantially increase artifacts during HRV measurement, especially atrial ectopic beats. Moreover, HRV may be altered by various factors (duration and time of measurement, breathing, drugs, and other confounding factors) that alter each metric in different ways. The Standard Deviation of all Normal to Normal intervals (SDNN) is the most commonly used metric to evaluate HRV in oncology, but it does not appear to be specific to the cardiac vagal tone. Thus, cardiac vagal activity diagnosis and vital prognosis of cancer patients can be biased. Our review presents the main HRV metrics that can be currently used in oncology studies and their links with vagus nerve and cancer. We present the influence of external factors and the required duration and time of measurement. Considering all these parameters, this review proposes seven key points for an assessment of HRV and cardiac vagal tone in patients with cancer.

Reference values for heart rate variability in older adults: A systematic review.

Heart rate variability (HRV) is an early marker of risk for various health conditions, and its analysis serves as a valuable tool for assessing older adults. This study aimed to describe the reference values of HRV parameters in older adults through a systematic review of the literature. The review included searches in MEDLINE (via PubMed®), EMBASE, Latin American and Caribbean Health Literature, Scopus, and Web of Science (WOS). Studies presenting reference values for at least one HRV linear analysis measure in older adults were considered eligible. Out of 1618 studies identified, only 11 met the inclusion criteria. Sample sizes of older adults ranged from 21 to 6250 subjects. The HRV measures assessed (mean RR intervals, SDNN, RMSSD, PNN50, LF, HF, and LF/HF ratio) varied significantly between studies, with no standardized methods for HRV analysis. We concluded that reference values for HRV measures in older adults vary widely between studies. The scientific literature on HRV reference values in older adults is still limited, and future studies should standardize assessment methods for HRV measures in this population.

Feasibility of Short-Term Use of Ivabradine in Critical Ill Patients Who Have Atrial Fibrillation and Tachycardia.

Background: Ivabradine is approved for heart rate reduction in patients with stable symptomatic heart failure (HF). The United States Food and Drug Administration and Taiwan Central Health Insurance Agency approved the use of ivabradine for patients with chronic stable HF with sinus rhythm, but it has not yet been approved for patients with acute decompensated HF or with atrial fibrillation (AF). Objectives: To investigate whether short-term ivabradine use is feasible in critically ill patients with AF and rapid ventricular response (RVR). Methods: This study retrospectively analyzed 23 patients admitted to an intensive care unit with acute HF and AF-RVR who received ivabradine. All patients initially received a slow IV of amiodarone. Other medications for HF were prescribed according to current HF guidelines. The time taken for ivabradine to reduce HR to 80 beats per minute, referred to as "Time to 80," was measured in each patient. Results: Overall, 69.6 % (16/23) of the patients had New York Heart Association functional class IV HF. In addition, 60.9% (14/23) of the patients required endotracheal intubation and ventilatory support, with more than half receiving vasopressor treatment to manage hypotension. Five patients died during the study period. The surviving patients had a significantly shorter "Time to 80" compared to those who did not survive (p = 0.037). Conclusions: Adding ivabradine to standard treatment might be feasible for critically ill patients with AF and tachycardia. The finding that surviving patients had a shorter "Time to 80" duration than those who did not survive may have clinical implications. However, further investigations are needed to assess its clinical utility.

Sex differences in achieving guideline-recommended heart rate control among a large sample of patients at risk for sudden cardiac arrest.

Background: Despite known clinical benefits, guideline-recommended heart rate (HR) control is not achieved for a significant proportion of patients with HF with reduced ejection fraction. The wearable cardioverter-defibrillator (WCD) provides continuous HR monitoring and alerts that could aid medication titration. Objective: This study sought to evaluate sex differences in achieving guideline-recommended HR control during a period of WCD use. Methods: Data from patients fitted with a WCD from 2015 to 2018 were obtained from the manufacturer's database (ZOLL). The proportion of patients with adequate nighttime resting HR control at the beginning of use (BOU) and at the end of use (EOU) were compared by sex. Adequate HR control was defined as having a nighttime median HR <70 beats/min. Results: A total of 21,440 women and a comparative sample of 17,328 men (median 90 [IQR 59-116] days of WCD wear) were included in the final dataset. Among patients who did not receive a shock, over half had insufficient HR control at BOU (59% of women, 53% of men). Although the proportion of patients with resting HR ≥70 beats/min improved by EOU, 43% of women and 36% of men did not achieve guideline-recommended HR control. Conclusion: A significant proportion of women and men did not achieve adequate HR control during a period of medical therapy optimization. Compared with men, a greater proportion of women receiving WCD shocks had insufficiently controlled HR in the week preceding ventricular tachyarrhythmia/ventricular fibrillation and 43% of nonshocked women, compared with 36% of men, did not reach adequate HR control during the study period. The WCD can be utilized as a remote monitoring tool to record HR and inform adequate uptitration of beta-blockers, with particular focus on reducing the treatment gap in women.