The impact of ventricular remodeling on quality-of-life outcomes after Transcatheter aortic valve replacement.

BACKGROUND: Among patients with aortic stenosis, ventricular remodeling by hypertrophy can limit the augmentation of flow with exertion, even after valve intervention. However, the effect of hypertrophy on quality of life (QoL) improvement has not been studied. We aimed to determine the effect of ventricular hypertrophy on QoL outcomes after transcatheter aortic valve replacement (TAVR). METHODS: All patients undergoing TAVR from 2011 to 2021 at our institution were included. Groups were divided into none/mild ventricular hypertrophy (non-remodeled, NR) and moderate/severe left ventricular hypertrophy (VH) according to guideline-recommended cut-offs for left ventricular (LV) wall thickness. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was utilized to assess QoL; primary outcome was KCCQ change <5 from baseline to 30 days and 1 year. RESULTS: We analyzed 679 patients (NR: N = 389, VH: N = 290). Groups differed by septal thickness (1.12 cm vs. 1.44 cm, p < 0.001), posterior wall thickness (1.08 cm vs. 1.33 cm, p < 0.001), and LV internal diastolic diameter (4.34 cm vs. 4.19 cm, p = 0.006). The primary outcome was similar between NR and VH at 30 days (31.6 % vs. 28.6 %, p = 0.449) and 1 year (27.7 % vs. 21.5 %, p = 0.217). NR and VH experienced similar proportions of worsening, no change, or small, moderate, and large improvements in KCCQ score. Both groups experienced similar domain score changes and New York Heart Association class improvement. A subgroup analysis of VH patients did not reveal interaction with cavity size or stroke volume. CONCLUSION: Patients with significant ventricular remodeling by hypertrophy and aortic stenosis have similar QoL changes after intervention compared to patients without significant remodeling.

Rationale and design of OPT-RATE AF: A randomized clinical trial of increased physiologic pacing rates in heart failure with preserved ejection fraction.

Cardiac physiologic pacing (CPP) after atrioventricular node (AVN) ablation for persistent atrial fibrillation (AF) has improved outcomes in patients with heart failure with reduced and preserved ejection fraction (HFpEF). Emerging evidence suggests patients with HFpEF benefit from higher heart rates, yet the optimal pacing rate after AVN ablation remains unknown. OPT-RATE AF is a prospective, randomized crossover study of patients with HFpEF following AVN ablation for persistent AF (NCT06445439). Approximately 60 patients with AF and AVN ablation, CPP, and HF with left ventricular ejection fraction ≥50% will be enrolled. Participants will be randomly assigned 1:1 to a pacing lower rate limit of 60 beats-per-minute (bpm) for 3 months and then switched to a rate of 80 bpm for 3 months, and vice versa. The primary endpoint is change in exercise capacity assessed by the 6-minute walk test. Notable secondary outcomes will include change in Kansas City Quality of Life Questionnaire (KCCQ-12), creatinine and natriuretic peptide, and clinical events. Patient mortality and HF hospitalizations will be recorded at each phase. EKG, echocardiogram, pacemaker interrogation, and primary and secondary outcomes will be recorded at baseline, 3 months, and 6 months. Study enrollment is ongoing and estimated to be completed by 2026. OPT-RATE AF is a randomized clinical trial that will determine the effect of a higher pacing rate in patients with persistent AF and HFpEF following AVN ablation and/or CPP. Study findings will provide insight on the role of chronotropy in improving QoL and other important cardiovascular outcomes.

Assessment of sociodemographic factors associated with time to self-reported COVID-19 infection among a large multi-center prospective cohort population in the southeastern United States.

OBJECTIVE: We aimed to investigate sociodemographic factors associated with self-reported COVID-19 infection. METHODS: The study population was a prospective multicenter cohort of adult volunteers recruited from healthcare systems located in the mid-Atlantic and southern United States. Between April 2020 and October 2021, participants completed daily online questionnaires about symptoms, exposures, and risk behaviors related to COVID-19, including self-reports of positive SARS CoV-2 detection tests and COVID-19 vaccination. Analysis of time from study enrollment to self-reported COVID-19 infection used a time-varying mixed effects Cox-proportional hazards framework. RESULTS: Overall, 1,603 of 27,214 study participants (5.9%) reported a positive COVID-19 test during the study period. The adjusted hazard ratio demonstrated lower risk for women, those with a graduate level degree, and smokers. A higher risk was observed for healthcare workers, those aged 18-34, those in rural areas, those from households where a member attends school or interacts with the public, and those who visited a health provider in the last year. CONCLUSIONS: We identified subgroups within healthcare network populations defined by age, occupational exposure, and rural location reporting higher than average rates of COVID-19 infection for our surveillance population. These subgroups should be monitored closely in future epidemics of respiratory viral diseases.

Cost-Effectiveness of Sotagliflozin in SOLOIST-WHF.

BACKGROUND: The efficacy of sotagliflozin in patients with diabetes and recent worsening of heart failure was shown in the SOLOIST-WHF trial. However, the cost-effectiveness of sotagliflozin in these patients has not been previously investigated. OBJECTIVES: The authors sought to determine the cost-effectiveness of sotagliflozin in patients with diabetes and recent worsening of heart failure. METHODS: Based on SOLOIST-WHF trial data (N = 1,222), the authors constructed a Markov model to estimate the lifetime impact of sotagliflozin from a U.S. health care sector perspective. Cost data were sourced from the National Inpatient Sample. Life expectancy was modeled from census data and modified by the mortality rate in SOLOIST-WHF. Fatal and nonfatal event rates were carried forward from the trial data. Utility was assessed from the published reports. RESULTS: Lifetime quality-adjusted life-years (QALYs) were 4.43 and 4.04 in the sotagliflozin and placebo groups, respectively, and lifetime costs were $220,113 and $188,198 in the sotagliflozin and placebo groups, respectively. The point estimate incremental cost-effectiveness ratio was $81,823 per QALY gained. The probability of being cost-effective was 3.6%, 67.5%, and 89.4% at willingness-to-pay thresholds of $50,000, $100,000, and $150,000, respectively, per QALY gained. CONCLUSIONS: In patients with diabetes and recent worsening of heart failure, sotagliflozin is cost-effective in the U.S. using commonly accepted willingness-to-pay thresholds. (Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure [SOLOIST-WHF]; NCT03521934).

A Technology-Assisted Web Application for Consumer Access to a Nonprescription Statin Medication.

BACKGROUND: Although statins reduce adverse cardiovascular outcomes, less than one-half of eligible patients receive treatment. A nonprescription statin has the potential to improve access to statins. OBJECTIVES: This study sought to assess concordance between clinician and consumer assessment of eligibility for nonprescription statin treatment using a technology assisted self-selection Web application (Web App) and evaluate effect on low-density lipoprotein cholesterol (LDL-C) levels. METHODS: This study was a prospective actual use 6-month study to evaluate use of a Web App to qualify participants without a medical background for a moderate-intensity statin based on current guidelines. Participants entered demographic information, cholesterol values, blood pressure, and concomitant medications into the Web App, resulting in 3 possible outcomes: "do not use," "ask a doctor," and "OK to use." RESULTS: The study included 1,196 participants, with a median age of 63 years (Q1-Q3: 57-68 years); 39.6% were women, 79.3% were White, 11.7% were Black, and 4.1% had limited literacy. Mean LDL-C was 139.6 ± 28.3 mg/dL and the median calculated 10-year risk of atherosclerotic cardiovascular disease was 10.1% (Q1-Q3: 7.3%-14.0%). Initial Web App self-selection resulted in an outcome concordant with clinician assessment in 90.7% (95% CI: 88.9%-92.3%) of participants, and 98.1% (95% CI: 97.1%-98.8%) had a concordant final use outcome during treatment. Mean percent change in LDL-C was -35.5% (95% CI: -36.6% to -34.3%). Serious adverse events occurred in 27 (2.3%) participants, none related to the study drug. CONCLUSIONS: In this actual use study, a technology-assisted Web App allowed >90% of consumers to correctly self-select for statin use and achieve clinically important LDL-C reductions. (Technology-Assisted Cholesterol Trial in Consumers [TACTiC]; NCT04964544).

From chest pain to coronary functional testing: Clinical and economic impact of coronary microvascular dysfunction.

BACKGROUND: Coronary functional testing to formally diagnose coronary microvascular dysfunction (CMD) reduces cardiovascular events and alleviates angina. This study aims to investigate the extensive and complex journey that patients with CMD undergo, from the onset of chest pain to eventual diagnosis. METHODS: Data from the Coronary Microvascular Disease Registry (CMDR) were analyzed, including information on the date of first documentation of chest pain, number of non-invasive and invasive tests the patient underwent, emergency department visits, and hospitalizations. In addition, we estimated the total cost per patient. A total of 61 patients with CMD diagnosis were included in this analysis. RESULTS: Most patients in our cohort were older than 50 years of age. The median time from initial chest pain symptoms to diagnosis was 0.62 (interquartile range [IQR]: 0.06-2.96) years. During this period, patients visited the emergency department a median of 1.0 (IQR: 0.0-2.0) times. Diagnostic tests included 3.0 (IQR: 2.0-6.0) electrocardiograms, 3.0 (IQR: 0.0-6.0) high-sensitivity troponin tests, and 1.0 (IQR: 1.0-2.0) echocardiograms. Prior to diagnosis of CMD, 13 (21.3 %) patients had left heart catheterization without coronary functional testing. Non-invasive testing for ischemia was conducted in 43 (70.5 %) patients. Alternative non-cardiac diagnoses were given to 11 (18.0 %) patients during the diagnostic process, with referrals made to gastroenterology for 16 (26.2 %) and pulmonology for 10 (16.4 %) patients. The cost was almost $2000/patient. CONCLUSION: Timely identification of CMD offers promising opportunities for prompt symptom alleviation, accompanied by reduced visits to the emergency department, cardiovascular testing, invasive medical procedures, and consequently reduced healthcare expenses.

Disease-State Understanding and Experience of Patients Receiving Continuous Intravenous Inotropic Support as Palliative Therapy: A Multicenter Survey.

Background: The use of continuous intravenous inotropic support (CIIS) as palliative therapy in patients with advanced heart failure (HF) has increased over the past decade. CIIS improves New York Heart Association (NYHA) functional class but does not impact survival. Objective: The objective of this study was to examine patients' understanding of the therapeutic intent of CIIS, prognostic awareness, and quality of life with CIIS. Design: We conducted a prospective, cross-sectional, multicenter study of patients with advanced HF receiving CIIS as palliative therapy between 2020 and 2022. Settings/Subjects: An investigator-developed survey instrument was administered to outpatients on CIIS in the United States via telephone. Measurements: Survey data were analyzed using descriptive and inferential statistics. Results: Forty-eight patients, 63% male, 81% African American/Black, with a mean age of 68.9 (standard deviation 12.3) years, participated in this study. The majority of patients responded that they expected CIIS to make them feel better (79%) and increase longevity (75%), but few expected that CIIS would cure their HF (19%). Patients described their overall quality of life on CIIS as not better/worse (19%), somewhat better (46%), and significantly better (35%) and reported high treatment satisfaction (87% were at least somewhat satisfied). Conclusions: In this study, patients report improved quality of life with CIIS as palliative therapy. Patients on CIIS as palliative therapy expected increased survival on CIIS, which is incongruent with current evidence. Further studies on how we can improve care processes so that patients have accurate prognostic and disease-state awareness, and receive goal concordant care, are warranted.

Cost of Cardiovascular Disease Event and Cardiovascular Disease Treatment-Related Complication Hospitalizations in the United States.

BACKGROUND: Cardiovascular disease (CVD) is among the costliest conditions in the United States, and cost-effectiveness analyses can be used to assess economic impact and prioritize CVD treatments. We aimed to develop standardized, nationally representative CVD events and selected possible CVD treatment-related complication hospitalization costs for use in cost-effectiveness analyses. METHODS: Nationally representative costs were derived using publicly available inpatient hospital discharge data from the 2012-2018 National Inpatient Sample. Events were identified using the principal International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes. Facility charges were converted to costs using charge-to-cost ratios, and total costs were estimated by applying a published professional fee ratio. All costs are reported in 2021 US dollars. Mean costs were estimated for events overall and stratified by age, sex, and survival status at discharge. Annual costs to the US health care system were estimated by multiplying the mean annual number of events by the mean total cost per discharge. RESULTS: The annual mean number of hospital discharges among CVD events was the highest for heart failure (1 087 000 per year) and cerebrovascular disease (800 600 per year). The mean cost per hospital discharge was the highest for peripheral vascular disease ($33 700 [95% CI, $33 300-$34 000]) and ventricular tachycardia/ventricular fibrillation ($32 500 [95% CI, $32 100-$32 900]). Hospitalizations contributing the most to annual US health care costs were heart failure ($19 500 [95% CI, $19 300-$19 800] million) and acute myocardial infarction ($18 300, [95% CI, $18 200-$18 500] million). Acute kidney injury was the most frequent possible treatment complication (515 000 per year), and bradycardia had the highest mean hospitalization costs ($17 400 [95% CI, $17 200-$17 500]). CONCLUSIONS: The hospitalization cost estimates and statistical code reported in the current study have the potential to increase transparency and comparability of cost-effectiveness analyses for CVD in the United States.

Accuracy of Noninvasive Blood Pressure Monitoring in Critically Ill Adults.

Background: Blood pressure (BP) is routinely invasively monitored by an arterial catheter in the intensive care unit (ICU). However, the available data comparing the accuracy of noninvasive methods to arterial catheters for measuring BP in the ICU are limited by small numbers and diverse methodologies. Purpose: To determine agreement between invasive arterial blood pressure monitoring (IABP) and noninvasive blood pressure (NIBP) in critically ill patients. Methods: This was a single center, observational study of critical ill adults in a tertiary care facility evaluating agreement (≤10% difference) between simultaneously measured IABP and NIBP. We measured clinical features at time of BP measurement inclusive of patient demographics, laboratory data, severity of illness, specific interventions (mechanical ventilation and dialysis), and vasopressor dose to identify particular clinical scenarios in which measurement agreement is more or less likely. Results: Of the 1852 critically ill adults with simultaneous IABP and NIBP readings, there was a median difference of 6 mm Hg in mean arterial pressure (MAP), interquartile range (1-12), P < .01. A logistic regression analysis identified 5 independent predictors of measurement discrepancy: increasing doses of norepinephrine (adjusted odds ratio [aOR] 1.10 [95% confidence interval, CI 1.08-1.12] P = .03 for every change in 5 µg/min), lower MAP value (aOR 0.98 [0.98-0.99] P < .01 for every change in 1 mm Hg), higher body mass index (aOR 1.04 [1.01-1.09] P = .01 for an increase in 1), increased patient age (aOR 1.31 [1.30-1.37] P < .01 for every 10 years), and radial arterial line location (aOR 1.74 [1.16-2.47] P = .04). Conclusions: There was broad agreement between IABP and NIBP in critically ill patients over a range of BPs and severity of illness. Several variables are associated with measurement discrepancy; however, their predictive capacity is modest. This may guide future study into which patients may specifically benefit from an arterial catheter.

Effectiveness of Hypertension Management Strategies in SPRINT-Eligible US Adults: A Simulation Study.

BACKGROUND: Despite reducing cardiovascular disease (CVD) events and death in SPRINT (Systolic Blood Pressure Intervention Trial), intensive systolic blood pressure goals have not been adopted in the United States. This study aimed to simulate the potential long-term impact of 4 hypertension management strategies in SPRINT-eligible US adults. METHODS AND RESULTS: The validated Blood Pressure Control-Cardiovascular Disease Policy Model, a discrete event simulation of hypertension care processes (ie, visit frequency, blood pressure [BP] measurement accuracy, medication intensification, and medication adherence) and CVD outcomes, was populated with 25 000 SPRINT-eligible US adults. Four hypertension management strategies were simulated: (1) usual care targeting BP <140/90 mm Hg (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care), (2) intensive care per the SPRINT protocol targeting BP <120/90 mm Hg (SPRINT intensive), (3) usual care targeting guideline-recommended BP <130/80 mm Hg (American College of Cardiology/American Heart Association usual care), and (4) team-based care added to usual care and targeting BP <130/80 mm Hg. Relative to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, among the 18.1 million SPRINT-eligible US adults, an estimated 138 100 total CVD events could be prevented per year with SPRINT intensive, 33 900 with American College of Cardiology/American Heart Association usual care, and 89 100 with team-based care. Compared with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, SPRINT intensive care was projected to increase treatment-related serious adverse events by 77 600 per year, American College of Cardiology/American Heart Association usual care by 33 300, and team-based care by 27 200. CONCLUSIONS: As BP control has declined in recent years, health systems must prioritize hypertension management and invest in effective strategies. Adding team-based care to usual care may be a pragmatic way to manage risk in this high-CVD-risk population.

Cost-Effectiveness of Icosapent Ethyl in REDUCE-IT USA: Results From Patients Randomized in the United States.

BACKGROUND: In 3146 REDUCE-IT USA (Reduction of Cardiovascular Events With Icosapent Ethyl Intervention Trial USA) participants, icosapent ethyl (IPE) reduced first and total cardiovascular events by 31% and 36%, respectively, over 4.9 years of follow-up. METHODS AND RESULTS: We used participant-level data from REDUCE-IT USA, 2021 US costs, and IPE costs ranging from $4.59 to $11.48 per day, allowing us to examine a range of possible medication costs. The in-trial analysis was participant-level, whereas the lifetime analysis used a Markov model. Both analyses considered value from a US health sector perspective. The incremental cost-effectiveness ratio (incremental costs divided by incremental quality-adjusted life-years) of IPE compared with standard care (SC) was the primary outcome measure. There was incremental gain in quality-adjusted life-years with IPE compared with SC using in-trial (3.28 versus 3.13) and lifetime (10.36 versus 9.83) horizons. Using an IPE cost of $4.59 per day, health care costs were lower with IPE compared with SC for both in-trial ($29 420 versus $30 947) and lifetime ($216 243 versus $219 212) analyses. IPE versus SC was a dominant strategy in trial and over the lifetime, with 99.7% lifetime probability of an incremental cost-effectiveness ratio <$50 000 per quality-adjusted life-year gained. At a medication cost of $11.48 per day, the cost per quality-adjusted life-year gained was $36 208 in trial and $9582 over the lifetime. CONCLUSIONS: In this analysis, at $4.59 per day, IPE offers better outcomes than SC at lower costs in trial and over a lifetime and is cost-effective at $11.48 per day for conventional willingness-to-pay thresholds. Treatment with IPE should be strongly considered in US patients like those enrolled in REDUCE-IT USA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

Quality control-driven deep ensemble for accountable automated segmentation of cardiac magnetic resonance LGE and VNE images.

Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is the gold standard for non-invasive myocardial tissue characterisation. However, accurate segmentation of the left ventricular (LV) myocardium remains a challenge due to limited training data and lack of quality control. This study addresses these issues by leveraging generative adversarial networks (GAN)-generated virtual native enhancement (VNE) images to expand the training set and incorporating an automated quality control-driven (QCD) framework to improve segmentation reliability. Methods: A dataset comprising 4,716 LGE images (from 1,363 patients with hypertrophic cardiomyopathy and myocardial infarction) was used for development. To generate additional clinically validated data, LGE data were augmented with a GAN-based generator to produce VNE images. LV was contoured on these images manually by clinical observers. To create diverse candidate segmentations, the QCD framework involved multiple U-Nets, which were combined using statistical rank filters. The framework predicted the Dice Similarity Coefficient (DSC) for each candidate segmentation, with the highest predicted DSC indicating the most accurate and reliable result. The performance of the QCD ensemble framework was evaluated on both LGE and VNE test datasets (309 LGE/VNE images from 103 patients), assessing segmentation accuracy (DSC) and quality prediction (mean absolute error (MAE) and binary classification accuracy). Results: The QCD framework effectively and rapidly segmented the LV myocardium (<1 s per image) on both LGE and VNE images, demonstrating robust performance on both test datasets with similar mean DSC (LGE: 0.845±0.075; VNE: 0.845±0.071; p=ns). Incorporating GAN-generated VNE data into the training process consistently led to enhanced performance for both individual models and the overall framework. The quality control mechanism yielded a high performance (MAE=0.043, accuracy=0.951) emphasising the accuracy of the quality control-driven strategy in predicting segmentation quality in clinical settings. Overall, no statistical difference (p=ns) was found when comparing the LGE and VNE test sets across all experiments. Conclusions: The QCD ensemble framework, leveraging GAN-generated VNE data and an automated quality control mechanism, significantly improved the accuracy and reliability of LGE segmentation, paving the way for enhanced and accountable diagnostic imaging in routine clinical use.

Determinants of Health and Outcomes in Medicare Recipients With Heart Disease: A Population Study.

CONTEXT: Heart disease (HD) is a primary cause of mortality and morbidity in the United States. While there is a growing body of evidence demonstrating the contribution of social determinants of health (SDoH) to HD outcomes, the impact of combined or individual SDoH on health-related quality of life (HRQoL) in patients with HD is not well understood. OBJECTIVES: To analyze the National Health and Aging Trends Study (NHATS) to explore the relationship of SDoH with HRQoL, advance care planning, and treatment preferences in Medicare beneficiaries with HD. METHODS: The study design was a secondary data analysis using latent class analysis (LCA) and multivariable analysis of NHATS participants with HD, Round 8, that included End of Life Plans and Care questions. RESULTS: 1202 participants, median age 81 years, 57% female, 70% non-Hispanic White, 20% non-Hispanic Black, 10% Other. LCA identified two SDoH risk profiles (low/high), using 12 measures within the NHATS Economic and Social Consequences key concept area. The high-risk SDoH profile participants were more likely to have fair/poor HRQoL, and identify as female, non-White (P < 0.0001); and less likely to have completed advance care planning (P < 0.0001). High-risk SDoH participants were more likely to want life-prolonging treatments (P < 0.0001), however, this association was not significant after adjusting for age, sex, and race (P = 0.344). CONCLUSION: Higher risk SDoH profiles are associated with reduced HRQoL, reduced advance care planning completion, female sex, and non-White race in a cohort of Medicare beneficiaries. These findings provide opportunities to improve SDoH-related care practices in older patients with HD.