Accuracy and consistency of online large language model-based artificial intelligence chat platforms in answering patients' questions about heart failure.

BACKGROUND: Heart failure (HF) is a prevalent condition associated with significant morbidity. Patients may have questions that they feel embarrassed to ask or will face delays awaiting responses from their healthcare providers which may impact their health behavior. We aimed to investigate the potential of large language model (LLM) based artificial intelligence (AI) chat platforms in complementing the delivery of patient-centered care. METHODS: Using online patient forums and physician experience, we created 30 questions related to diagnosis, management and prognosis of HF. The questions were posed to two LLM-based AI chat platforms (OpenAI's ChatGPT-3.5 and Google's Bard). Each set of answers was evaluated by two HF experts, independently and blinded to each other, for accuracy (adequacy of content) and consistency of content. RESULTS: ChatGPT provided mostly appropriate answers (27/30, 90%) and showed a high degree of consistency (93%). Bard provided a similar content in its answers and thus was evaluated only for adequacy (23/30, 77%). The two HF experts' grades were concordant in 83% and 67% of the questions for ChatGPT and Bard, respectively. CONCLUSION: LLM-based AI chat platforms demonstrate potential in improving HF education and empowering patients, however, these platforms currently suffer from issues related to factual errors and difficulty with more contemporary recommendations. This inaccurate information may pose serious and life-threatening implications for patients that should be considered and addressed in future research.

A novel automated peak frequency annotation algorithm for identifying deceleration zones and ventricular tachycardia ablation sites.

BACKGROUND: Current annotation of local fractionated signals during ventricular electroanatomic mapping (EAM) requires manual input subject to variability and error. OBJECTIVES: The purpose of this study was to evaluate a novel peak frequency (PF) annotation software for its ability to automatically detect late potentials (LPs) and local abnormal ventricular activity (LAVA), determine an optimal range for display, and assess its impact on isochronal late activation mapping (ILAM). METHODS: EAM data from 25 patients who underwent ventricular tachycardia (VT) ablation were retrospectively analyzed. Samplings of electrogram PFs from areas of normal bipolar voltage, areas of low voltage, and areas of low voltage with fractioned signals were performed. An optimal range of frequency display was identified from these patients and applied to a validation cohort of 10 prospective patients to assess high PF within scar as a predictor of VT ablation target sites, in particular deceleration zones (DZs) identified by ILAM, LP, and LAVA. RESULTS: Voltage and PF ranges of normal endocardial tissue varied widely. Using 220 Hz as a frequency cutoff value in areas of low bipolar voltage, areas of high fractionation were identified with sensitivity of 91% and specificity of 85% There was no significant reduction in targeted DZ surface areas, and colocalization with DZs was observed in all cases. Applied to the prospective cohort, PF predicted fractionated areas and DZ in 9 of 10 patients. CONCLUSION: A PF annotation algorithm with a cutoff of 220 Hz accurately identifies areas of fractioned signals and accurately predicts DZs during ILAM.

Associations of Adipokine Levels with Levels of Remnant Cholesterol: the Multi-Ethnic Study of Atherosclerosis (MESA).

Background: The metabolic syndrome phenotype of individuals with obesity is characterized by elevated levels of triglyceride (TG)-rich lipoproteins and remnant particles, which have been shown to be significantly atherogenic. Understanding the association between adipokines, endogenous hormones produced by adipose tissue, and remnant cholesterol (RC) would give insight into the link between obesity and atherosclerotic cardiovascular disease. Methods: We studied 1,791 MESA participants of an ancillary study on body composition who had adipokine levels measured (leptin, adiponectin, resistin) at either visit 2 or 3. RC was calculated as non-high density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDL-C), measured at the same visit as the adipokines, as well as subsequent visits 4 through 6. Multivariable-adjusted linear mixed effects models were used to assess the cross-sectional and longitudinal associations between adipokines and levels of RC. Results: Mean (SD) age was 64.5±9.6 years and for body mass index (BMI) was 29.9±5.0 kg/m2; 52.0% were women. In fully adjusted models that included BMI, LDL-C and lipid-lowering therapy, for each 1-unit increment in adiponectin, there was 14.4% (12.0, 16.8) lower RC. With each 1-unit increment in leptin and resistin, there was 4.5% (2.3, 6.6) and 5.1% (1.2, 9.2) higher RC, respectively. Lower adiponectin and higher leptin were also associated with longitudinal increases in RC levels over median follow-up of 5(4-8) years. Conclusions: Lower adiponectin and higher leptin levels were independently associated with higher levels of RC at baseline and longitudinal RC increase, even after accounting for BMI and LDL-C. CLINICAL PERSPECTIVE: What is new?: - Among individuals without history of cardiovascular disease, adiponectin is inversely associated with cross-sectional levels of remnant cholesterol, whereas leptin and resistin are directly associated.- Adiponectin had an inverse association with progression of remnant cholesterol levels over time.What are the clinical implications?: - Adiponectin levels were not associated with LDL-C levels but with levels of triglyceride-rich lipoproteins, particularly remnant cholesterol.-Incrementing adiponectin via lifestyle modification and/or pharmacological therapies (i.e. GLP-1 agonists) could be a mechanism to reduce remnant cholesterol levels and ultimately cardiovascular risk.

Understanding Cardiology Practitioners' Interpretations of Electrocardiograms: An Eye-Tracking Study.

BACKGROUND: Visual expertise refers to advanced visual skills demonstrated when performing domain-specific visual tasks. Prior research has emphasized the fact that medical experts rely on such perceptual pattern-recognition skills when interpreting medical images, particularly in the field of electrocardiogram (ECG) interpretation. Analyzing and modeling cardiology practitioners' visual behavior across different levels of expertise in the health care sector is crucial. Namely, understanding such acquirable visual skills may help train less experienced clinicians to interpret ECGs accurately. OBJECTIVE: This study aims to quantify and analyze through the use of eye-tracking technology differences in the visual behavior and methodological practices for different expertise levels of cardiology practitioners such as medical students, cardiology nurses, technicians, fellows, and consultants when interpreting several types of ECGs. METHODS: A total of 63 participants with different levels of clinical expertise took part in an eye-tracking study that consisted of interpreting 10 ECGs with different cardiac abnormalities. A counterbalanced within-subjects design was used with one independent variable consisting of the expertise level of the cardiology practitioners and two dependent variables of eye-tracking metrics (fixations count and fixation revisitations). The eye movements data revealed by specific visual behaviors were analyzed according to the accuracy of interpretation and the frequency with which interpreters visited different parts/leads on a standard 12-lead ECG. In addition, the median and SD in the IQR for the fixations count and the mean and SD for the ECG lead revisitations were calculated. RESULTS: Accuracy of interpretation ranged between 98% among consultants, 87% among fellows, 70% among technicians, 63% among nurses, and finally 52% among medical students. The results of the eye fixations count, and eye fixation revisitations indicate that the less experienced cardiology practitioners need to interpret several ECG leads more carefully before making any decision. However, more experienced cardiology practitioners rely on their skills to recognize the visual signal patterns of different cardiac abnormalities, providing an accurate ECG interpretation. CONCLUSIONS: The results show that visual expertise for ECG interpretation is linked to the practitioner's role within the health care system and the number of years of practical experience interpreting ECGs. Cardiology practitioners focus on different ECG leads and different waveform abnormalities according to their role in the health care sector and their expertise levels.

Systemic Inflammation May Induce Cardiac Injury in COVID-19 Patients Including Children and Adolescents Without Underlying Cardiovascular Diseases: A Systematic Review.

Coronavirus disease 2019(COVID-19) is an ongoing global pandemic with a daily increasing number of affected individuals and a relatively high mortality rate. COVID-19 patients that develop cardiac injury are at increased risk of a worse clinical course with higher rates of mortality. Increasing amounts of evidence suggest that a system-wide inflammatory response and a cytokine storm mediated type syndrome plays a crucial role in disease progression. This systematic review investigates the possible role of hyperinflammation in inducing cardiac injury as one of the severe complications of COVID-19. A systematic literature search was performed using PubMed, Embase and Scopus databases to identify relevant clinical studies that investigated cardiovascular injury manifestations and reported inflammatory and cardiac biomarkers in COVID-19 patients. Only 29 studies met our inclusion criteria and the majority of these studies demonstrated significantly elevated inflammatory and cardiac blood markers. It was evident that underlying cardiovascular diseases may increase the risk of developing cardiac injury. However, many COVID-19 patients included in this review, developed different types of cardiac injury without having any underlying cardiovascular diseases. Furthermore, many of these patients were either children or adolescents. Therefore, age and comorbidities may not always be the two main risk factors that dictate the severity and outcome of COVID-19. Further investigations are required to understand the underlying mechanisms of pathogenicity as an urgent requirement to develop the appropriate treatment and prevention strategies. These strategies may specifically target hyperinflammation as a suspected driving factor for some of the severe complications of COVID-19.

Cardiovascular and haematological events post COVID-19 vaccination: A systematic review.

Since COVID-19 took a strong hold around the globe causing considerable morbidity and mortality, a lot of effort was dedicated to manufacturing effective vaccines against SARS-CoV-2. Many questions have since been raised surrounding the safety of the vaccines, and a lot of media attention to certain side effects. This caused a state of vaccine hesitancy that may prove problematic in the global effort to control the virus. This review was undertaken with the aim of putting together all the reported cardiovascular and haematological events post COVID-19 vaccination in published literature and to suggest possible mechanisms to explain these rare phenomena.

Systemic inflammation in COVID-19 patients may induce various types of venous and arterial thrombosis: A systematic review.

COVID-19 is a global pandemic with a daily increasing number of affected individuals. Thrombosis is a severe complication of COVID-19 that leads to a worse clinical course with higher rates of mortality. Multiple lines of evidence suggest that hyperinflammation plays a crucial role in disease progression. This review compiles clinical data of COVID-19 patients who developed thrombotic complications to investigate the possible role of hyperinflammation in inducing hypercoagulation. A systematic literature search was performed using PubMed, Embase, Medline and Scopus to identify relevant clinical studies that investigated thrombotic manifestations and reported inflammatory and coagulation biomarkers in COVID-19 patients. Only 54 studies met our inclusion criteria, the majority of which demonstrated significantly elevated inflammatory markers. In the cohort studies with control, D-dimer was significantly higher in COVID-19 patients with thrombosis as compared to the control. Pulmonary embolism, deep vein thrombosis and strokes were frequently reported which could be attributed to the hyperinflammatory response associated with COVID-19 and/or to the direct viral activation of platelets and endothelial cells, two mechanisms that are discussed in this review. It is recommended that all admitted COVID-19 patients should be assessed for hypercoagulation. Furthermore, several studies have suggested that anticoagulation may be beneficial, especially in hospitalized non-ICU patients. Although vaccines against SARS-CoV-2 have been approved and distributed in several countries, research should continue in the field of prevention and treatment of COVID-19 and its severe complications including thrombosis due to the emergence of new variants against which the efficacy of the vaccines is not yet clear.

Comparison of Methods to Estimate Low-Density Lipoprotein Cholesterol in Patients With High Triglyceride Levels.

Importance: Low-density lipoprotein cholesterol (LDL-C) is typically estimated with the Friedewald or Martin/Hopkins equation; however, if triglyceride levels are 400 mg/dL or greater, laboratories reflexively perform direct LDL-C (dLDL-C) measurement. The use of direct chemical LDL-C assays and estimation of LDL-C via the National Institutes of Health Sampson equation are not well validated, and data on the accuracy of LDL-C estimation at higher triglyceride levels are limited. Objective: To compare an extended Martin/Hopkins equation for triglyceride values of 400 to 799 mg/dL with the Friedewald and Sampson equations. Design, Setting, and Participants: This cross-sectional study evaluated consecutive patients at clinical sites across the US with patient lipid distributions representative of the US population in the Very Large Database of Lipids from January 1, 2006, to December 31, 2015, with triglyceride levels of 400 to 799 mg/dL. Data analysis was performed from November 9, 2020, to March 23, 2021. Main Outcomes and Measures: Accuracy in LDL-C classification according to guideline-based categories and absolute errors between estimated LDL-C and dLDL-C levels. Patients were randomly assigned 2:1 to derivation and validation data sets. Levels of dLDL-C were measured by vertical spin-density gradient ultracentrifugation. The LDL-C levels were estimated using the Friedewald method, with a fixed ratio of triglycerides to very low-density lipoprotein cholesterol (VLDL-C ratio of 5:1), extended Martin/Hopkins equation with a flexible ratio, and Sampson equation with VLDL-C estimation by multiple least-squares regression. Results: A total of 111 939 patients (mean [SD] age, 52 [13] years; 65.0% male) with triglyceride levels of 400 to 799 mg/dL were included, representing 2.2% of 5 081 680 patients in the database. Across all individual guideline LDL-C classes (<40, 40-69, 70-99, 100-129, 130-159, 160-189, and ≥190), estimation of LDL-C by the extended Martin/Hopkins equation was most accurate (62.1%) compared with the Friedewald (19.3%) and Sampson (40.4%) equations. In classifying LDL-C levels less than 70 mg/dL across all triglyceride strata, the extended Martin/Hopkins equation was most accurate (67.3%) compared with Friedewald (5.1%) and Sampson (26.4%) equations. In addition, for classifying LDL-C levels less than 40 mg/dL across all triglyceride strata, the extended Martin/Hopkins equation was most accurate (57.2%) compared with the Friedewald (4.3%) and Sampson (14.4%) equations. However, considerable underclassification of LDL-C occurred. The magnitude of error between the Martin/Hopkins equation estimation and dLDL-C was also smaller: at LDL-C levels less than 40 mg/dL, 2.7% of patients had 30 mg/dL or greater differences between dLDL-C and estimated LDL-C using the Martin/Hopkins equation compared with the Friedewald (92.5%) and Sampson (38.7%) equations. Conclusions and Relevance: In this cross-sectional study, the extended Martin/Hopkins equation offered greater LDL-C accuracy compared with the Friedewald and Sampson equations in patients with triglyceride levels of 400 to 799 mg/dL. However, regardless of method used, caution is advised with LDL-C estimation in this triglyceride range.

Interpretation of a 12-Lead Electrocardiogram by Medical Students: Quantitative Eye-Tracking Approach.

BACKGROUND: Accurate interpretation of a 12-lead electrocardiogram (ECG) demands high levels of skill and expertise. Early training in medical school plays an important role in building the ECG interpretation skill. Thus, understanding how medical students perform the task of interpretation is important for improving this skill. OBJECTIVE: We aimed to use eye tracking as a tool to research how eye fixation can be used to gain a deeper understanding of how medical students interpret ECGs. METHODS: In total, 16 medical students were recruited to interpret 10 different ECGs each. Their eye movements were recorded using an eye tracker. Fixation heatmaps of where the students looked were generated from the collected data set. Statistical analysis was conducted on the fixation count and duration using the Mann-Whitney U test and the Kruskal-Wallis test. RESULTS: The average percentage of correct interpretations was 55.63%, with an SD of 4.63%. After analyzing the average fixation duration, we found that medical students study the three lower leads (rhythm strips) the most using a top-down approach: lead II (mean=2727 ms, SD=456), followed by leads V1 (mean=1476 ms, SD=320) and V5 (mean=1301 ms, SD=236). We also found that medical students develop a personal system of interpretation that adapts to the nature and complexity of the diagnosis. In addition, we found that medical students consider some leads as their guiding point toward finding a hint leading to the correct interpretation. CONCLUSIONS: The use of eye tracking successfully provides a quantitative explanation of how medical students learn to interpret a 12-lead ECG.

Kidney Transplant Recipients Infected With Coronavirus Disease 2019: Retrospective Qatar Experience.

BACKGROUND: This study aimed to evaluate the incidence of coronavirus disease 2019 (COVID-19) infection on kidney transplant, mortality, and risk factors associated with infection acquisition and severe illness in kidney transplant recipients with COVID-19. METHODS: Of 693 kidney transplant recipients who reported to our center, 249 were tested for COVID-19 by throat and nasal swab reverse transcription polymerase chain reaction. Of these, 43 recipients tested positive and 206 recipients tested negative. Among the 43 positive recipients, 9 were treated within an isolation facility, 25 were admitted to the hospital, and 9 were admitted to the intensive care unit (ICU). Risk factors associated with positive results and ICU admission were evaluated. RESULTS: COVID-19 was found in 6% of transplant recipients. Asian ethnicity (p = .003), history of hypertensive nephropathy (p = .01), AB blood group (P = .04), and higher tacrolimus trough levels (P = .007) were more frequent in the COVID-19 positive than in the COVID-19 negative group. ICU admission was more frequent in recipients presenting with fever, shortness of breath, and acute allograft dysfunction. Renal replacement therapy was required in 3 (7%) of 43 recipients, and mortality was reported in 1 (2.3%) recipient. Acute allograft dysfunction was an independent risk factor for severe COVID-19 (odds ratio, 93.7; 95% confidence interval, 2.37-3710.94; P = .02). CONCLUSIONS: Higher tacrolimus targets may be associated with COVID-19 development. Acute kidney injury during the COVID-19 course may be a sign of severe disease. Prognostication of COVID-19 severity in kidney transplant recipients is crucial for early recognition of critical illness and may ensure early intervention.

New Antidiabetes Medications and Their Cardiovascular and Renal Benefits.

After 12 years of rigorous cardiovascular outcome trials (CVOTs), sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) emerged as new therapeutic options for patients with type 2 diabetes mellitus to reduce the risk of heart disease. SGLT2i additionally cause a reduction in heart failure and renal events in patients both with and without diabetes. This article reviews the major CVOTs that support the use of these agents, describes the mechanisms of action that lead to their broad cardiorenal benefits, explains current guidelines, and offers practical clinical advice to initiate and monitor treatment with these agents.

Atrial fibrillation catheter ablation complications in obese and diabetic patients: Insights from the US Nationwide Inpatient Sample 2005-2013.

BACKGROUND: Obesity and diabetes are risk factors for atrial fibrillation (AF) incidence and recurrence after catheter ablation. However, their impact on post-ablation complications in real-world practice is unknown. OBJECTIVES: We examine annual trends in AF ablations and procedural outcomes in obese and diabetic patients in the US and whether obesity and diabetes are independently associated with adverse outcomes. METHODS: Using the Nationwide Inpatient Sample (2005-2013), we identified obese and diabetic patients admitted for AF ablation. Common complications were identified using ICD-9-CM codes. The primary outcome included the composite of any in-hospital complication or death. Annual trends of the primary outcome, length-of-stay (LOS) and total-inflation adjusted hospital charges were examined. Multivariate analyses studied the association of obesity and diabetes with outcomes. RESULTS: An estimated 106 462 AF ablations were performed in the US from 2005 to 2013. Annual trends revealed a gradual increase in ablations performed in obese and diabetic patients and in complication rates. The overall rate of the primary outcome in obese was 11.7% versus 8.2% in non-obese and 10.7% in diabetic versus 8.2% in non-diabetic patients (p < .001). CONCLUSIONS: Obesity was independently associated with increased complications (adjusted OR, 95% CI:1.39, 1.20-1.62), longer LOS (1.36, 1.23-1.49), and higher charges (1.16, 1.12-1.19). Diabetes was only associated with longer LOS (1.27, 1.16-1.38). Obesity, but not diabetes, in patients undergoing AF ablation is an independent risk factor for immediate post-ablation complications and higher costs. Future studies should investigate whether weight loss prior to ablation reduces complications and costs.

LDL-C-lowering therapies reduce major vascular events in patients aged ≥75 y.

SOURCE CITATION: Gencer B, Marston NA, Im K, et al. Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020;396:1637-43. 33186535.

Smart wearable devices in cardiovascular care: where we are and how to move forward.

Technological innovations reach deeply into our daily lives and an emerging trend supports the use of commercial smart wearable devices to manage health. In the era of remote, decentralized and increasingly personalized patient care, catalysed by the COVID-19 pandemic, the cardiovascular community must familiarize itself with the wearable technologies on the market and their wide range of clinical applications. In this Review, we highlight the basic engineering principles of common wearable sensors and where they can be error-prone. We also examine the role of these devices in the remote screening and diagnosis of common cardiovascular diseases, such as arrhythmias, and in the management of patients with established cardiovascular conditions, for example, heart failure. To date, challenges such as device accuracy, clinical validity, a lack of standardized regulatory policies and concerns for patient privacy are still hindering the widespread adoption of smart wearable technologies in clinical practice. We present several recommendations to navigate these challenges and propose a simple and practical 'ABCD' guide for clinicians, personalized to their specific practice needs, to accelerate the integration of these devices into the clinical workflow for optimal patient care.

The Interplay Between the Immune System, the Renin-Angiotensin-Aldosterone System (RAAS), and RAAS Inhibitors May Modulate the Outcome of COVID-19: A Systematic Review.

Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), numerous research has been undertaken to delineate the various effects of the virus which manifests in many ways all over the body. The association between the SARS-CoV-2 invasion mechanism and the renin-angiotensin-aldosterone system (RAAS) receptors, created many debates about the possible consequences of using RAAS-modulating drugs including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) during the pandemic. Many clinical studies were conducted to assess the outcomes of coronavirus disease 2019 (COVID-19) in patients who use ACEi/ARBs following the arguments claiming to discontinue these drugs as a precautionary measure. Although several studies mainly analyzed the outcomes of the disease, this review aimed to compare specific blood markers in both groups of COVID-19 patients to gain better insight into the interaction of ACEi/ARBs with different body functions during the infection. Several databases were searched using a combination of keywords followed by screening and data extraction. Only 28 studies met our inclusion criteria, the majority of which showed no significant difference between the inflammation markers of COVID-19 patients who used or did not use ACEi/ARBs. Interestingly, 6 studies reported lower inflammatory markers in COVID-19 patients who used ACEi/ARBs, and 6 studies reported better outcomes among the same group. We therefore concluded that the use of ACEi/ARBs may not lead to worse prognosis of COVID-19 and may even play a protective role against the hyperinflammatory response associated with COVID-19.

Attenuated heart rate recovery is associated with higher arrhythmia recurrence and mortality following atrial fibrillation ablation.

AIMS: Heart rate recovery (HRR), the decrease in heart rate occurring immediately after exercise, is caused by the increase in vagal activity and sympathetic withdrawal occurring after exercise and is a powerful predictor of cardiovascular events and mortality. The extent to which it impacts outcomes of atrial fibrillation (AF) ablation has not previously been studied. The aim of this study is to investigate the association between attenuated HRR and outcomes following AF ablation. METHODS AND RESULTS: We studied 475 patients who underwent EST within 12 months of AF ablation. Patients were categorized into normal (>12 b.p.m.) and attenuated (≤12 b.p.m.) HRR groups. Our main outcomes of interest included arrhythmia recurrence and all-cause mortality. During a mean follow-up of 33 months, 43% of our study population experienced arrhythmia recurrence, 74% of those with an attenuated HRR, and 30% of those with a normal HRR (P < 0.0001). Death occurred in 9% of patients in the attenuated HRR group compared to 4% in the normal HRR cohort (P = 0.001). On multivariable models adjusting for cardiorespiratory fitness (CRF), medication use, left atrial size, ejection fraction, and renal function, attenuated HRR was predictive of increased arrhythmia recurrence (hazard ratio 2.54, 95% confidence interval 1.86-3.47, P < 0.0001). CONCLUSION: Heart rate recovery provides additional valuable prognostic information beyond CRF. An impaired HRR is associated with significantly higher rates of arrhythmia recurrence and death following AF ablation.

Exercise Ventricular Rates, Cardiopulmonary Exercise Performance, and Mortality in Patients With Heart Failure With Atrial Fibrillation.

BACKGROUND: In heart failure (HF) with sinus rhythm, resting and exercise heart rates correlate with exercise capacity and mortality. However, in HF with atrial fibrillation (AF), this correlation is unknown. Our aim is to investigate the association of resting and exercise ventricular rates (VRs) with exercise capacity and mortality in HF with AF. METHODS: We identified 903 patients with HF and AF referred for cardiopulmonary stress testing. AF was defined as history of AF and AF during cardiopulmonary stress testing. We constructed multivariable models to evaluate the association of resting VR, peak exercise VR, VR reserve (peak VR-resting VR), and chronotropic index with (1) peak oxygen consumption (PVO2) ≤18 mL/kg per minute, (2) continuous PVO2, and (3) 10-year all-cause mortality. RESULTS: Median (25th-75th percentile) age was 60 (52-67) years, left ventricular ejection fraction was 25 (15-50)%, and 76.1% were males. Patients with lower (quartile 1) compared with higher (quartile 4) peak VR, VR reserve, and chronotropic index were more likely to have PVO2 ≤18 mL/kg per min (adjusted odds ratio [95% CI]: 14.92 [8.07-27.58], 24.60 [12.36-48.98], and 22.31 [11.24-44.27], respectively), and higher all-cause mortality (adjusted hazard ratio [95% CI]: 2.56 [1.62-4.04], 2.29 [1.47-3.59], and 2.30 [1.51-3.49], respectively). For every 10 beats per minute increase in VR reserve, PVO2 increased by 1.05 mL/kg per minute (B-coefficient [95% CI]: 1.05 [0.94-1.15]) and mortality decreased by 12% (adjusted hazard ratio [95% CI]: 0.88 [0.83-0.94]). Resting VR was associated with PVO2 (B-coefficient [95% CI]: -0.46 [-0.70 to -0.23]) but not mortality (adjusted hazard ratio [95% CI]: 0.97 [0.88-1.06]). CONCLUSIONS: In patients with HF and AF, higher resting VR and lower peak exercise VR, VR reserve, and chronotropic index were all associated with worse peak exercise capacity, but only lower exercise VR parameters were associated with higher mortality. Dedicated studies are needed to gauge whether modulating exercise VR enhances exercise performance and outcomes.