Journal: JAMA Cardiol

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<div><h4>Association of Rurality With Risk of Heart Failure.</h4><i>Turecamo SE, Xu M, Dixon D, Powell-Wiley TM, ... Lipworth L, Roger VL</i><br /><b>Importance</b><br />Rural populations experience an increased burden of heart failure (HF) mortality compared with urban populations. Whether HF incidence is greater among rural individuals is less known. Additionally, the intersection between racial and rural health inequities is understudied.<br /><b>Objective</b><br />To determine whether rurality is associated with increased risk of HF, independent of cardiovascular (CV) disease and socioeconomic status (SES), and whether rurality-associated HF risk varies by race and sex.<br /><b>Design, setting, and participants</b><br />This prospective cohort study analyzed data for Black and White participants of the Southern Community Cohort Study (SCCS) without HF at enrollment who receive care via Centers for Medicare & Medicaid Services (CMS). The SCCS is a population-based cohort of low-income, underserved participants from 12 states across the southeastern United States. Participants were enrolled between 2002 and 2009 and followed up until December 31, 2016. Data were analyzed from October 2021 to November 2022.<br /><b>Exposures</b><br />Rurality as defined by Rural-Urban Commuting Area codes at the census-tract level.<br /><b>Main outcomes and measures</b><br />Heart failure was defined using diagnosis codes via CMS linkage through 2016. Incidence of HF was calculated by person-years of follow-up and age-standardized. Sequentially adjusted Cox proportional hazards regression models tested the association between rurality and incident HF.<br /><b>Results</b><br />Among 27 115 participants, the median (IQR) age was 54 years (47-65), 18 647 (68.8%) were Black, and 8468 (32.3%) were White; 5556 participants (20%) resided in rural areas. Over a median 13-year follow-up, age-adjusted HF incidence was 29.6 (95% CI, 28.9-30.5) per 1000 person-years for urban participants and 36.5 (95% CI, 34.9-38.3) per 1000 person-years for rural participants (P < .001). After adjustment for demographic information, CV risk factors, health behaviors, and SES, rural participants had a 19% greater risk of incident HF (hazard ratio [HR], 1.19; 95% CI, 1.13-1.26) compared with their urban counterparts. The rurality-associated risk of HF varied across race and sex and was greatest among Black men (HR, 1.34; 95% CI, 1.19-1.51), followed by White women (HR, 1.22; 95% CI, 1.07-1.39) and Black women (HR, 1.18; 95% CI, 1.08-1.28). Among White men, rurality was not associated with greater risk of incident HF (HR, 0.97; 95% CI, 0.81-1.16).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among predominantly low-income individuals in the southeastern United States, rurality was associated with an increased risk of HF among women and Black men, which persisted after adjustment for CV risk factors and SES. This inequity points to a need for additional emphasis on primary prevention of HF among rural populations.<br /><br /><br /><br /><small>JAMA Cardiol: 25 Jan 2023; epub ahead of print</small></div>
Turecamo SE, Xu M, Dixon D, Powell-Wiley TM, ... Lipworth L, Roger VL
JAMA Cardiol: 25 Jan 2023; epub ahead of print | PMID: 36696094
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<div><h4>Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial.</h4><i>Wheeler MT, Olivotto I, Elliott PM, Saberi S, ... Oreziak A, Myers J</i><br /><b>Importance</b><br />Mavacamten, a cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the EXPLORER-HCM study. However, the full extent of mavacamten\'s effects on exercise performance remains unclear.<br /><b>Objective</b><br />To investigate the effect of mavacamten on exercise physiology using cardiopulmonary exercise testing (CPET).<br /><b>Design, setting, and participants</b><br />Exploratory analyses of the data from the EXPLORER-HCM study, a randomized, double-blind, placebo-controlled, phase 3 trial that was conducted in 68 cardiovascular centers in 13 countries. In total, 251 patients with symptomatic obstructive HCM were enrolled.<br /><b>Interventions</b><br />Patients were randomly assigned in a 1:1 ratio to mavacamten or placebo.<br /><b>Main outcomes and measures</b><br />The following prespecified exploratory cardiovascular and performance parameters were assessed with a standardized treadmill or bicycle ergometer test protocol at baseline and week 30: carbon dioxide output (VCO2), minute ventilation (VE), peak VE/VCO2 ratio, ventilatory efficiency (VE/VCO2 slope), peak respiratory exchange ratio (RER), peak circulatory power, ventilatory power, ventilatory threshold, peak metabolic equivalents (METs), peak exercise time, partial pressure of end-tidal carbon dioxide (PETCO2), and VO2/workload slope.<br /><b>Results</b><br />Two hundred fifty-one patients were enrolled. The mean (SD) age was 58.5 (11.9) years and 59% of patients were male. There were significant improvements with mavacamten vs placebo in the following peak-exercise CPET parameters: peak VE/VCO2 ratio (least squares [LS] mean difference, -2.2; 95% CI, -3.05 to -1.26; P < .001), peak METs (LS mean difference, 0.4; 95% CI, 0.17-0.60; P < .001), peak circulatory power (LS mean difference, 372.9 mL/kg/min × mm Hg; 95% CI, 153.12-592.61; P = .001), and peak PETCO2 (LS mean difference, 2.0 mm Hg; 95% CI, 1.12-2.79; P < .001). Mavacamten also improved peak exercise time compared with placebo (LS mean difference, 0.7 minutes; 95% CI, 0.13-1.24; P = .02). There was a significant improvement in nonpeak-exercise CPET parameters, such as VE/VCO2 slope (LS mean difference, -2.6; 95% CI, -3.58 to -1.52; P < .001) and ventilatory power (LS mean difference, 0.6 mm Hg; 95% CI, 0.29-0.90; P < .001) favoring mavacamten vs placebo.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Mavacamten improved a range of CPET parameters beyond pVO2, indicating consistent and broad benefits on maximal exercise capacity. Although improvements in peak-exercise CPET parameters are clinically meaningful, the favorable effects of mavacamten on submaximal exertional tolerance provide further insights into the beneficial impact of mavacamten in patients with obstructive HCM.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03470545.<br /><br /><br /><br /><small>JAMA Cardiol: 18 Jan 2023; epub ahead of print</small></div>
Wheeler MT, Olivotto I, Elliott PM, Saberi S, ... Oreziak A, Myers J
JAMA Cardiol: 18 Jan 2023; epub ahead of print | PMID: 36652223
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<div><h4>Association of Plasma High-Density Lipoprotein Cholesterol Level With Risk of Fractures in Healthy Older Adults.</h4><i>Hussain SM, Ebeling PR, Barker AL, Beilin LJ, Tonkin AM, McNeil JJ</i><br /><b>Importance</b><br />Increased levels of high-density lipoprotein cholesterol (HDL-C) have been associated with osteoporosis. Preclinical studies have reported that HDL-C reduces bone mineral density by reducing osteoblast number and function. However, the clinical significance of these findings is unclear.<br /><b>Objective</b><br />To determine whether higher HDL-C levels are predictive of an increased fracture risk in healthy older adults.<br /><b>Design, setting, and participants</b><br />This cohort study is a post hoc analysis of data from the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial and the ASPREE-Fracture substudy. ASPREE was a double-blind, randomized, placebo-controlled primary prevention trial of aspirin that recruited participants between 2010 and 2014. These comprised community-based older adults (16 703 Australians aged ≥70 years, 2411 US participants ≥65 years) without evident cardiovascular disease, dementia, physical disability, and life-limiting chronic illness. The ASPREE-Fracture substudy collected data on fractures reported postrandomization from Australian participants. Cox regression was used to calculate hazard ratio (HR) and 95% CI. Data analysis for this study was performed from April to August 2022.<br /><b>Exposure</b><br />Plasma HDL-C.<br /><b>Main outcomes and measures</b><br />Fractures included were confirmed by medical imaging and included both traumatic and minimal trauma fractures. Fractures were adjudicated by an expert review panel.<br /><b>Results</b><br />Of the 16 262 participants who had a plasma HDL-C measurement at baseline (8945 female participants [55%] and 7319 male [45%]), 1659 experienced at least 1 fracture over a median (IQR) of 4.0 years (0.02-7.0 years). In a fully adjusted model, each 1-SD increment in HDL-C level was associated with a 14% higher risk of fractures (HR, 1.14; 95% CI, 1.08-1.20). The results remained similar when these analyses were stratified by sex. Sensitivity and stratified analyses demonstrated that these associations persisted when the analyses were repeated to include only (1) minimal trauma fractures, (2) participants not taking osteoporosis medications, (3) participants who were never smokers and reported that they did not drink alcohol, and (4) participants who walked outside for less than 30 minutes per day and reported no participation in moderate/vigorous physical activity and to examine only (5) statin use. No association was observed between non-HDL-C levels and fractures.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />This study suggests that higher levels of HDL-C are associated with an increased fracture risk. This association was independent of common risk factors for fractures.<br /><br /><br /><br /><small>JAMA Cardiol: 18 Jan 2023; epub ahead of print</small></div>
Hussain SM, Ebeling PR, Barker AL, Beilin LJ, Tonkin AM, McNeil JJ
JAMA Cardiol: 18 Jan 2023; epub ahead of print | PMID: 36652261
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<div><h4>Frailty and Effects of a Multidomain Physical Rehabilitation Intervention Among Older Patients Hospitalized for Acute Heart Failure: A Secondary Analysis of a Randomized Clinical Trial.</h4><i>Pandey A, Kitzman DW, Nelson MB, Pastva AM, ... Upadhya B, Reeves GR</i><br /><b>Importance</b><br />Frailty is common among older patients with acute decompensated heart failure (ADHF) and is associated with worse quality of life (QOL) and a higher risk of clinical events. Frailty can also limit recovery and response to interventions. In the Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial, a 3-month innovative, early, transitional, tailored, multidomain physical rehabilitation intervention improved physical function and QOL (vs usual care) in older patients with ADHF.<br /><b>Objective</b><br />To evaluate whether baseline frailty modified the benefits of the physical rehabilitation intervention among patients with ADHF enrolled in the REHAB-HF trial and to assess the association between changes in frailty with the risk of adverse clinical outcomes on follow-up.<br /><b>Design, setting, and participants</b><br />This prespecified secondary analysis of the REHAB-HF trial, a multicenter randomized clinical trial, included 337 patients 60 years and older hospitalized for ADHF. Patients were enrolled from September 17, 2014, through September 19, 2019. Participants were stratified across baseline frailty strata as assessed using modified Fried criteria. Data were analyzed from July 2021 to September 2022.<br /><b>Interventions</b><br />Physical rehabilitation intervention or attention control.<br /><b>Main outcomes and measures</b><br />Primary outcome was the Short Physical Performance Battery (SPPB) score at 3 months. Clinical outcomes included all-cause hospitalization or mortality at 6 months.<br /><b>Results</b><br />This prespecified secondary analysis included 337 participants; 181 (53.7%) were female, 167 (49.6%) were Black, and the mean (SD) age was 72 (8) years. A total of 192 (57.0%) were frail and 145 (43.0%) were prefrail at baseline. A significant interaction was observed between baseline frailty status and the treatment arm for the primary trial end point of overall SPPB score, with a 2.6-fold larger improvement in SPPB with intervention among frail patients (2.1; 95% CI, 1.3-2.9) vs prefrail patients (0.8; 95% CI, -0.1 to 1.6; P for interaction = .03). Trends consistently favored a larger intervention effect size, with significant improvement among frail vs prefrail participants for 6-minute walk distance, QOL, and the geriatric depression score, but interactions did not achieve significance.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this prespecified secondary analysis of the REHAB-HF trial, patients with ADHF with worse baseline frailty status had a more significant improvement in physical function in response to an innovative, early, transitional, tailored, multidomain physical rehabilitation intervention than those who were prefrail.<br /><b>Trial registration</b><br />Clinical Trials.gov Identifier: NCT02196038.<br /><br /><br /><br /><small>JAMA Cardiol: 04 Jan 2023; epub ahead of print</small></div>
Pandey A, Kitzman DW, Nelson MB, Pastva AM, ... Upadhya B, Reeves GR
JAMA Cardiol: 04 Jan 2023; epub ahead of print | PMID: 36598761
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<div><h4>Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention.</h4><i>Marston NA, Pirruccello JP, Melloni GEM, Koyama S, ... Sabatine MS, Ruff CT</i><br /><b>Importance</b><br />The clinical utility of polygenic risk scores (PRS) for coronary artery disease (CAD) has not yet been established.<br /><b>Objective</b><br />To investigate the ability of a CAD PRS to potentially guide statin initiation in primary prevention after accounting for age and clinical risk.<br /><b>Design, setting, and participants</b><br />This was a longitudinal cohort study with enrollment starting on January 1, 2006, and ending on December 31, 2010, with data updated to mid-2021, using data from the UK Biobank, a long-term population study of UK citizens. A replication analysis was performed in Biobank Japan. The analysis included all patients without a history of CAD and who were not taking lipid-lowering therapy. Data were analyzed from January 1 to June 30, 2022.<br /><b>Exposures</b><br />Polygenic risk for CAD was defined as low (bottom 20%), intermediate, and high (top 20%) using a CAD PRS including 241 genome-wide significant single-nucleotide variations (SNVs). The pooled cohort equations were used to estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk and classify individuals as low (<5%), borderline (5-<7.5%), intermediate (7.5-<20%), or high risk (≥20%).<br /><b>Main outcomes and measures</b><br />Myocardial infarction (MI) and ASCVD events (defined as incident clinical CAD [including MI], stroke, or CV death).<br /><b>Results</b><br />A total of 330 201 patients (median [IQR] age, 57 [40-74] years; 189 107 female individuals [57%]) were included from the UK Biobank. Over the 10-year follow-up, 4454 individuals had an MI. The CAD PRS was significantly associated with the risk of MI in all age groups but had significantly stronger risk prediction at younger ages (age <50 years: hazard ratio [HR] per 1 SD of PRS, 1.72; 95% CI, 1.56-1.89; age 50-60 years: HR, 1.46; 95% CI, 1.38-1.53; age >60 years: HR, 1.42; 95% CI, 1.37-1.48; P for interaction <.001). In patients younger than 50 years, those with high PRS had a 3- to 4-fold increased associated risk of MI compared with those in the low PRS category. A significant interaction between CAD PRS and age was replicated in Biobank Japan. When CAD PRS testing was added to the clinical ASCVD risk score in individuals younger than 50 years, 591 of 4373 patients (20%) with borderline risk were risk stratified into intermediate risk, warranting initiation of statin therapy and 3198 of 7477 patients (20%) with both borderline or intermediate risk were stratified as low risk, thus not warranting therapy.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Results of this cohort study suggest that the predictive ability of a CAD PRS was greater in younger individuals and can be used to better identify patients with borderline and intermediate clinical risk who should initiate statin therapy.<br /><br /><br /><br /><small>JAMA Cardiol: 28 Dec 2022; epub ahead of print</small></div>
Marston NA, Pirruccello JP, Melloni GEM, Koyama S, ... Sabatine MS, Ruff CT
JAMA Cardiol: 28 Dec 2022; epub ahead of print | PMID: 36576811
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<div><h4>Performance of Cardiovascular Risk Prediction Models Among People Living With HIV: A Systematic Review and Meta-analysis.</h4><i>Soares C, Kwok M, Boucher KA, Haji M, ... Wu WC, Erqou S</i><br /><b>Importance</b><br />Extant data on the performance of cardiovascular disease (CVD) risk score models in people living with HIV have not been synthesized.<br /><b>Objective</b><br />To synthesize available data on the performance of the various CVD risk scores in people living with HIV.<br /><b>Data sources</b><br />PubMed and Embase were searched from inception through January 31, 2021.<br /><b>Study selection</b><br />Selected studies (1) were chosen based on cohort design, (2) included adults with a diagnosis of HIV, (3) assessed CVD outcomes, and (4) had available data on a minimum of 1 CVD risk score.<br /><b>Data extraction and synthesis</b><br />Relevant data related to study characteristics, CVD outcome, and risk prediction models were extracted in duplicate. Measures of calibration and discrimination are presented in tables and qualitatively summarized. Additionally, where possible, estimates of discrimination and calibration measures were combined and stratified by type of risk model.<br /><b>Main outcomes and measures</b><br />Measures of calibration and discrimination.<br /><b>Results</b><br />Nine unique observational studies involving 75 304 people (weighted average age, 42 years; 59 490 male individuals [79%]) living with HIV were included. In the studies reporting these data, 86% were receiving antiretroviral therapy and had a weighted average CD4+ count of 449 cells/μL. Included in the study were current smokers (50%), patients with diabetes (5%), and patients with hypertension (25%). Ten risk prediction scores (6 in the general population and 4 in the HIV-specific population) were analyzed. Most risk scores had a moderate performance in discrimination (C statistic: 0.7-0.8), without a significant difference in performance between the risk scores of the general and HIV-specific populations. One of the HIV-specific risk models (Data Collection on Adverse Effects of Anti-HIV Drugs Cohort 2016) and 2 of the general population risk models (Framingham Risk Score [FRS] and Pooled Cohort Equation [PCE] 10 year) had the highest performance in discrimination. In general, models tended to underpredict CVD risk, except for FRS and PCE 10-year scores, which were better calibrated. There was substantial heterogeneity across the studies, with only a few studies contributing data for each risk score.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Results of this systematic review and meta-analysis suggest that general population and HIV-specific CVD risk models had comparable, moderate discrimination ability in people living with HIV, with a general tendency to underpredict risk. These results reinforce the current recommendations provided by the American College of Cardiology/American Heart Association guidelines to consider HIV as a risk-enhancing factor when estimating CVD risk.<br /><br /><br /><br /><small>JAMA Cardiol: 28 Dec 2022; epub ahead of print</small></div>
Soares C, Kwok M, Boucher KA, Haji M, ... Wu WC, Erqou S
JAMA Cardiol: 28 Dec 2022; epub ahead of print | PMID: 36576812
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<div><h4>Management Challenges in Patients Younger Than 65 Years With Severe Aortic Valve Disease: A Review.</h4><i>Baman JR, Medhekar AN, Malaisrie SC, McCarthy P, Davidson CJ, Bonow RO</i><br /><b>Importance</b><br />The management of aortic valve disease, including aortic stenosis and aortic regurgitation (AR), in younger adult patients (age <65 years) is complex, and the optimal strategy is often unclear, contingent on multiple anatomic and holistic factors.<br /><b>Observations</b><br />Traditional surgical approaches carry significant considerations, including compulsory lifelong anticoagulation for patients who receive a mechanical aortic valve replacement (AVR) and the risk of structural valvular deterioration and need for subsequent valve intervention in those who receive a bioprosthetic AVR. These factors are magnified in young adults who are considering pregnancy, for whom issues of anticoagulation and valve longevity are heightened. The Ross procedure has emerged as a promising alternative; however, its adoption is limited to highly specialized centers. Valve repair is an option for selected patients with AR. These treatment options offer varying degrees of durability and are associated with different risks and complications, especially for younger adult patients. Patient-centered care from a multidisciplinary valve team allows for discussion of the optimal timing of intervention and the advantages and disadvantages of the various treatment options.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />The management of severe aortic valve disease in adults younger than 65 years is complex, and there are numerous considerations with each management decision. While mechanical AVR and bioprosthetic AVR have historically been the standards of care, other options are emerging for selected patients but are not yet generalizable beyond specialized surgical centers. A detailed discussion by members of the multidisciplinary heart team and the patient is an integral part of the shared decision-making process.<br /><br /><br /><br /><small>JAMA Cardiol: 21 Dec 2022; epub ahead of print</small></div>
Baman JR, Medhekar AN, Malaisrie SC, McCarthy P, Davidson CJ, Bonow RO
JAMA Cardiol: 21 Dec 2022; epub ahead of print | PMID: 36542365
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<div><h4>Association of PCSK9 Loss-of-Function Variants With Risk of Heart Failure.</h4><i>Trudsø LC, Ghouse J, Ahlberg G, Bundgaard H, Olesen MS</i><br /><b>Importance</b><br />An animal (mouse) study indicated that deficiency of proprotein convertase subtilisin/kexin type 9 (PCSK9) causes cardiac remodeling and heart failure (HF). Cardiac remodeling after PCSK9-inhibitor treatment is a concern for patients and for development of treatment directed against PCSK9.<br /><b>Objective</b><br />To determine whether genetic variants in the PCSK9 gene are associated with altered cardiac structure, cardiac function, and HF in humans.<br /><b>Design, setting, participants</b><br />This was a nested case-control study within the UK Biobank. Between March 13, 2006, and October 1, 2010, the UK Biobank enrolled 502 480 individuals aged 40 to 69 years. This study focused on a subset of those individuals, who completed cardiac magnetic resonance (CMR) imaging and had available genetic data. Analyses were conducted between November 2, 2021, and October 28, 2022.<br /><b>Exposures</b><br />Carrier status of predicted loss-of-function (pLoF) PCSK9 variants, R46L missense variant, and a genetic risk score (GRS).<br /><b>Main outcomes and measures</b><br />A total of 11 CMR imaging measurements, generated using a machine learning algorithm, and HF diagnosis.<br /><b>Results</b><br />In up to 35 135 individuals with CMR images, 18 252 (52%) were female individuals, and mean (SD) age was 55.0 (7.4) years. No significant association between PCSK9 carrier status and CMR indices were found for left ventricular mass (pLoF: β = -1.01; 95% CI, -2.99 to 0.98; P = .32; R46L: β = -0.18; 95% CI, -0.55 to 0.19; P = .35; GRS: β = -0.19; 95% CI, -0.50 to 0.11; P = .22) and left ventricular ejection fraction (pLoF: β = 0.43; 95% CI, -1.32 to 2.18; P = .63; R46L: β = -0.19; 95% CI, -0.52 to 0.14; P = .26; GRS: β = -0.08; 95% CI, -0.35 to 0.20; P = .58) or HF (pLoF: odds ratio [OR], 1.14; 95% CI, 0.56-2.05; P = .69; R46L: OR, 0.99; 95% CI, 0.90-1.10; P = .91; GRS: OR, 1.04; 95% CI, 0.96-1.13; P = .32).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Results of this case-control study suggest that there was no association between PCSK9 genetic variants and altered cardiac structure, cardiac function, or HF in humans.<br /><br /><br /><br /><small>JAMA Cardiol: 21 Dec 2022; epub ahead of print</small></div>
Trudsø LC, Ghouse J, Ahlberg G, Bundgaard H, Olesen MS
JAMA Cardiol: 21 Dec 2022; epub ahead of print | PMID: 36542369
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<div><h4>Fundamental Pathobiology of Coronary Atherosclerosis and Clinical Implications for Chronic Ischemic Heart Disease Management-The Plaque Hypothesis: A Narrative Review.</h4><i>Stone PH, Libby P, Boden WE</i><br /><b>Importance</b><br />Recent clinical and imaging studies underscore that major adverse cardiac events (MACE) outcomes are associated not solely with severe coronary obstructions (ischemia hypothesis or stenosis hypothesis), but with the plaque burden along the entire coronary tree. New research clarifies the pathobiologic mechanisms responsible for plaque development/progression/destabilization leading to MACE (plaque hypothesis), but the translation of these insights to clinical management strategies has lagged. This narrative review elaborates the plaque hypothesis and explicates the current understanding of underlying pathobiologic mechanisms, the provocative destabilizing influences, the diagnostic and therapeutic implications, and their actionable clinical management approaches to optimize the management of patients with chronic coronary disease.<br /><b>Observations</b><br />Clinical trials of management strategies for patients with chronic coronary artery disease demonstrate that while MACE rate increases progressively with the anatomic extent of coronary disease, revascularization of the ischemia-producing obstruction does not forestall MACE. Most severely obstructive coronary lesions often remain quiescent and seldom destabilize to cause a MACE. Coronary lesions that later provoke acute myocardial infarction often do not narrow the lumen critically. Invasive and noninvasive imaging can identify the plaque anatomic characteristics (plaque burden, plaque topography, lipid content) and local hemodynamic/biomechanical characteristics (endothelial shear stress, plaque structural stress, axial plaque stress) that can indicate the propensity of individual plaques to provoke a MACE.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />The pathobiologic construct concerning the culprit region of a plaque most likely to cause a MACE (plaque hypothesis), which incorporates multiple convergent plaque features, informs the evolution of a new management strategy capable of identifying the high-risk portion of plaque wherever it is located along the course of the coronary artery. Ongoing investigations of high-risk plaque features, coupled with technical advances to enable prognostic characterization in real time and at the point of care, will soon enable evaluation of the entire length of the atheromatous coronary artery and broaden the target(s) of our therapeutic intervention to include all regions of the plaque (both flow limiting and nonflow limiting).<br /><br /><br /><br /><small>JAMA Cardiol: 14 Dec 2022; epub ahead of print</small></div>
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<div><h4>Structural Valve Deterioration After Self-Expanding Transcatheter or Surgical Aortic Valve Implantation in Patients at Intermediate or High Risk.</h4><i>O\'Hair D, Yakubov SJ, Grubb KJ, Oh JK, ... Popma JJ, Reardon MJ</i><br /><b>Importance</b><br />The frequency and clinical importance of structural valve deterioration (SVD) in patients undergoing self-expanding transcatheter aortic valve implantation (TAVI) or surgery is poorly understood.<br /><b>Objective</b><br />To evaluate the 5-year incidence, clinical outcomes, and predictors of hemodynamic SVD in patients undergoing self-expanding TAVI or surgery.<br /><b>Design, setting, and participants</b><br />This post hoc analysis pooled data from the CoreValve US High Risk Pivotal (n = 615) and SURTAVI (n = 1484) randomized clinical trials (RCTs); it was supplemented by the CoreValve Extreme Risk Pivotal trial (n = 485) and CoreValve Continued Access Study (n = 2178). Patients with severe aortic valve stenosis deemed to be at intermediate or increased risk of 30-day surgical mortality were included. Data were collected from December 2010 to June 2016, and data were analyzed from December 2021 to October 2022.<br /><b>Interventions</b><br />Patients were randomized to self-expanding TAVI or surgery in the RCTs or underwent self-expanding TAVI for clinical indications in the nonrandomized studies.<br /><b>Main outcomes and measures</b><br />The primary end point was the incidence of SVD through 5 years (from the RCTs). Factors associated with SVD and its association with clinical outcomes were evaluated for the pooled RCT and non-RCT population. SVD was defined as (1) an increase in mean gradient of 10 mm Hg or greater from discharge or at 30 days to last echocardiography with a final mean gradient of 20 mm Hg or greater or (2) new-onset moderate or severe intraprosthetic aortic regurgitation or an increase of 1 grade or more.<br /><b>Results</b><br />Of 4762 included patients, 2605 (54.7%) were male, and the mean (SD) age was 82.1 (7.4) years. A total of 2099 RCT patients, including 1128 who received TAVI and 971 who received surgery, and 2663 non-RCT patients who received TAVI were included. The cumulative incidence of SVD treating death as a competing risk was lower in patients undergoing TAVI than surgery (TAVI, 2.20%; surgery, 4.38%; hazard ratio [HR], 0.46; 95% CI, 0.27-0.78; P = .004). This lower risk was most pronounced in patients with smaller annuli (23 mm diameter or smaller; TAVI, 1.32%; surgery, 5.84%; HR, 0.21; 95% CI, 0.06-0.73; P = .02). SVD was associated with increased 5-year all-cause mortality (HR, 2.03; 95% CI, 1.46-2.82; P < .001), cardiovascular mortality (HR, 1.86; 95% CI, 1.20-2.90; P = .006), and valve disease or worsening heart failure hospitalizations (HR, 2.17; 95% CI, 1.23-3.84; P = .008). Predictors of SVD were developed from multivariate analysis.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />This study found a lower rate of SVD in patients undergoing self-expanding TAVI vs surgery at 5 years. Doppler echocardiography was a valuable tool to detect SVD, which was associated with worse clinical outcomes.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifiers: NCT01240902, NCT01586910, and NCT01531374.<br /><br /><br /><br /><small>JAMA Cardiol: 14 Dec 2022; epub ahead of print</small></div>
O'Hair D, Yakubov SJ, Grubb KJ, Oh JK, ... Popma JJ, Reardon MJ
JAMA Cardiol: 14 Dec 2022; epub ahead of print | PMID: 36515976
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<div><h4>Characteristics of Clinical Trial Sites for Novel Transcatheter Mitral and Tricuspid Valvular Therapies.</h4><i>Nathan AS, Reddy KP, Yang L, Eberly LA, ... Groeneveld PW, Fanaroff AC</i><br /><b>Importance</b><br />Racial and ethnic minority and socioeconomically disadvantaged patients have been underrepresented in randomized clinical trials. Efforts have focused on enhancing inclusion of minority groups at sites participating at clinical trials; however, there may be differences in the patient populations of the sites that participate in clinical trials.<br /><b>Objective</b><br />To identify any differences in the racial, ethnic, and socioeconomic composition of patient populations among candidate sites in the US that did vs did not participate in trials for novel transcatheter therapies.<br /><b>Design, setting, and participants</b><br />This cross-sectional analysis used Medicare Provider Claims from 2019 for patients admitted to hospitals in the US. All clinical trials for transcatheter mitral and tricuspid valve therapies and the hospitals participating in each of the trials were identified using ClinicalTrials.gov. Hospitals with active cardiac surgical programs that did not participate in the trials were also identified. Data analysis was performed between July 2021 and July 2022.<br /><b>Exposures</b><br />Multivariable linear regression models were used to identify differences in racial, ethnic, and socioeconomic characteristics among patients undergoing cardiac surgery or transcatheter aortic valve replacement at trial vs nontrial hospitals.<br /><b>Main outcome and measures</b><br />The main outcome of the study was participation in a clinical trial for novel transcatheter mitral or tricuspid valve therapies.<br /><b>Results</b><br />A total of 1050 hospitals with cardiac surgery programs were identified, of which 121 (11.5%) participated in trials for transcatheter mitral or tricuspid therapies. Patients treated in trial hospitals had a higher median zip code-based household income (difference of $5261; 95% CI, $2986-$7537), a lower Distressed Communities Index score (difference of 5.37; 95% CI, 2.59-8.15), and no significant difference in the proportion of patients dual eligible for Medicaid (difference of 0.86; 95% CI, -2.38 to 0.66). After adjusting for each of the socioeconomic indicators separately, there was less than 1% difference in the proportion of Black and Hispanic patients cared for at hospitals participating vs not participating in clinical trials.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this cohort study among candidate hospitals for clinical trials for transcatheter mitral or tricuspid valve therapies, trial hospitals took care of a more socioeconomically advantaged population than nontrial hospitals, with a similar proportion of Black and Hispanic patients. These data suggest that site selection efforts may improve enrollment of socioeconomically disadvantaged patients but may not improve the enrollment of Black and Hispanic patients.<br /><br /><br /><br /><small>JAMA Cardiol: 07 Dec 2022; epub ahead of print</small></div>
Nathan AS, Reddy KP, Yang L, Eberly LA, ... Groeneveld PW, Fanaroff AC
JAMA Cardiol: 07 Dec 2022; epub ahead of print | PMID: 36477493
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<div><h4>Associations Between New York Heart Association Classification, Objective Measures, and Long-term Prognosis in Mild Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial.</h4><i>Rohde LE, Zimerman A, Vaduganathan M, Claggett BL, ... McMurray JJV, Solomon SD</i><br /><b>Importance</b><br />Heart failure (HF) treatment recommendations are centered on New York Heart Association (NYHA) classification, such that most apparently asymptomatic patients are not eligible for disease-modifying therapies.<br /><b>Objectives</b><br />To assess within-patient variation in NYHA classification over time, the association between NYHA class and an objective measure of HF severity (N-terminal pro-B-type natriuretic peptide [NT-proBNP] level), and their association with long-term prognosis in the PARADIGM-HF trial.<br /><b>Design, setting, and participants</b><br />All patients in PARADIGM-HF were in NYHA class II or higher at baseline and were treated with sacubitril-valsartan during a 6- to 10-week run-in period before randomization. Patients classified as NYHA class I, II, and III in PARADIGM-HF were compared at randomization.<br /><b>Exposures</b><br />NYHA class at randomization after 6 to 10 weeks of the run-in period.<br /><b>Main outcomes and measures</b><br />Primary outcome was cardiovascular death or first HF hospitalization. Logistic regression models, areas under the receiver operating characteristic curve (AUC), kernel density estimation overlaps, and Cox proportional hazards models were used.<br /><b>Results</b><br />The analysis included 8326 patients with known NYHA classification at randomization. Of 389 patients in NYHA class I, 228 (58%) changed functional class during the first year after randomization. Level of NT-proBNP was a poor discriminator of NYHA classification: for NYHA class I vs II, the AUC was 0.51 (95% CI, 0.48-0.54). For NT-proBNP level, estimated kernel density overlap was 93% between NYHA class I vs II, 79% between NYHA I vs III, and 83% between NYHA II vs III. Patients classified as NYHA III displayed a distinctively higher rate of cardiovascular events (NYHA III vs I, hazard ratio [HR], 1.84; 95% CI, 1.44-2.37; NYHA III vs II, HR, 1.49; 95% CI, 1.35-1.64). Patients in NYHA class I and II revealed lower event rates (NYHA II vs I, HR, 1.24; 95% CI, 0.97-1.58). Stratification by NT-proBNP level (<1600 pg/mL or ≥1600 pg/mL) identified subgroups with distinctive risk, such that NYHA class I patients with high NT-proBNP levels (n = 175) had a numerically higher event rate than patients with low NT-proBNP levels from any NYHA class (vs I, HR, 3.43; 95% CI, 2.03-5.87; vs II, HR, 2.12; 95% CI, 1.58-2.86; vs III, HR, 1.37; 95% CI, 1.00-1.88).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, patients in NYHA class I and II overlapped substantially in objective measures and long-term prognosis. Physician-defined \"asymptomatic\" functional class concealed patients who were at substantial risk for adverse outcomes. NYHA classification might be limited to differentiate mild forms of HF.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT01035255.<br /><br /><br /><br /><small>JAMA Cardiol: 07 Dec 2022; epub ahead of print</small></div>
Rohde LE, Zimerman A, Vaduganathan M, Claggett BL, ... McMurray JJV, Solomon SD
JAMA Cardiol: 07 Dec 2022; epub ahead of print | PMID: 36477809
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<div><h4>Transforming Atrial Fibrillation Research to Integrate Social Determinants of Health: A National Heart, Lung, and Blood Institute Workshop Report.</h4><i>Benjamin EJ, Thomas KL, Go AS, Desvigne-Nickens P, ... Cooper LS, Al-Khatib SM</i><br /><b>Importance</b><br />Only modest attention has been paid to the contributions of social determinants of health to atrial fibrillation (AF) risk factors, diagnosis, symptoms, management, and outcomes. The diagnosis of AF provides unique challenges exacerbated by the arrhythmia\'s often paroxysmal nature and individuals\' disparate access to health care and technologies that facilitate detection. Social determinants of health affect access to care and management decisions for AF, increasing the likelihood of adverse outcomes among individuals who experience systemic disadvantages. Developing effective approaches to address modifiable social determinants of health requires research to eliminate the substantive inequities in health care delivery and outcomes in AF.<br /><b>Observations</b><br />The National Heart, Lung, and Blood Institute convened an expert panel to identify major knowledge gaps and research opportunities in the field of social determinants of AF. The workshop addressed the following social determinants: (1) socioeconomic status and access to care; (2) health literacy; (3) race, ethnicity, and racism; (4) sex and gender; (5) shared decision-making in systemically disadvantaged populations; and (6) place, including rurality, neighborhood, and community. Many individuals with AF have multiple adverse social determinants, which may cluster in the individual and in systemically disadvantaged places (eg, rural locations, urban neighborhoods). Cumulative disadvantages may accumulate over the life course and contribute to inequities in the diagnosis, management, and outcomes in AF.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Workshop participants identified multiple critical research questions and approaches to catalyze social determinants of health research that address the distinctive aspects of AF. The long-term aspiration of this work is to eradicate the substantive inequities in AF diagnosis, management, and outcomes across populations.<br /><br /><br /><br /><small>JAMA Cardiol: 07 Dec 2022; epub ahead of print</small></div>
Benjamin EJ, Thomas KL, Go AS, Desvigne-Nickens P, ... Cooper LS, Al-Khatib SM
JAMA Cardiol: 07 Dec 2022; epub ahead of print | PMID: 36478155
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<div><h4>Association of Interleukin 6 Inhibition With Ziltivekimab and the Neutrophil-Lymphocyte Ratio: A Secondary Analysis of the RESCUE Clinical Trial.</h4><i>Adamstein NH, Cornel JH, Davidson M, Libby P, ... Ekström K, Ridker PM</i><br /><b>Importance</b><br />The neutrophil-lymphocyte ratio (NLR) independently predicts atherosclerotic events and is a potential biomarker for residual inflammatory risk. Interleukin (IL) 1β inhibition reduces the NLR, but whether inhibition of IL-6, a cytokine downstream of IL-1, also lowers the NLR is uncertain.<br /><b>Objective</b><br />To evaluate whether ziltivekimab, a therapeutic monoclonal antibody targeting the IL-6 ligand, associates with a lower NLR compared with placebo.<br /><b>Design, setting, and participants</b><br />This was an exploratory post hoc analysis of Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody Mediated IL-6 Inhibition (RESCUE), a double-blind, randomized, placebo-controlled, phase 2 trial conducted from June 17, 2019, to January 14, 2020, with 24 weeks of follow-up. Participants were enrolled at 40 sites in the US and included adults aged 18 or older with moderate to severe chronic kidney disease and high-sensitivity C-reactive protein levels of 2 mg/L or greater. Data were analyzed from September 28, 2021, to October 2, 2022.<br /><b>Interventions</b><br />Participants were randomly assigned equally to placebo or ziltivekimab, 7.5 mg, 15 mg, or 30 mg, subcutaneously every 4 weeks.<br /><b>Main outcomes and measures</b><br />The primary outcome was the change in the NLR at 12 weeks.<br /><b>Results</b><br />A total of 264 participants (median [IQR] age, 68 [60-75] years; 135 men [51%]; 129 women [49%]) were enrolled, of which 187 (71%) had diabetes, and 126 (48%) had known atherosclerosis. The median (IQR) change in the NLR at 12 weeks was 1.56% (IQR, -15.7% to 20.0%), -13.5% (IQR, -31.6% to 3.20%), -14.3% (IQR, -26.9% to 4.62%), and -22.4% (IQR, -33.3% to -4.27%) in the placebo, 7.5-mg, 15-mg, and 30-mg groups, respectively. The estimated treatment difference compared with placebo was -14.6% (95% CI, -24.8% to -4.81%; P = .004), -15.3% (95% CI, -25.2% to -5.10%; P = .004), and -23.6% (95% CI, -33.2% to -14.2%; P < .001) in the 7.5-mg, 15-mg, and 30-mg groups, respectively. A similar reduction in the absolute neutrophil count was observed.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Results of this post hoc analysis of the RESCUE trial show that IL-6 ligand inhibition with ziltivekimab associates with a lower NLR, suggesting that it may disrupt multiple atherogenic inflammatory pathways, including those mediated by the myeloid cell compartment. The NLR may have use in monitoring ziltivekimab\'s efficacy should it be introduced into clinical practice.<br /><br /><br /><br /><small>JAMA Cardiol: 30 Nov 2022; epub ahead of print</small></div>
Adamstein NH, Cornel JH, Davidson M, Libby P, ... Ekström K, Ridker PM
JAMA Cardiol: 30 Nov 2022; epub ahead of print | PMID: 36449307
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<div><h4>Effect of Smartphone Dispatch of Volunteer Responders on Automated External Defibrillators and Out-of-Hospital Cardiac Arrests: The SAMBA Randomized Clinical Trial.</h4><i>Berglund E, Hollenberg J, Jonsson M, Svensson L, ... Riva G, Ringh M</i><br /><b>Importance</b><br />Smartphone dispatch of volunteer responders to nearby out-of-hospital cardiac arrests (OHCAs) has emerged in several emergency medical services, but no randomized clinical trials have evaluated the effect on bystander use of automated external defibrillators (AEDs).<br /><b>Objective</b><br />To evaluate if bystander AED use could be increased by smartphone-aided dispatch of lay volunteer responders with instructions to collect nearby AEDs compared with instructions to go directly to patients with OHCAs to start cardiopulmonary resuscitation (CPR).<br /><b>Design, setting, and participants</b><br />This randomized clinical trial assessed a system for smartphone dispatch of volunteer responders to individuals experiencing OHCAs that was triggered at emergency dispatch centers in response to suspected OHCAs and randomized 1:1. The study was conducted in 2 main Swedish regions: Stockholm and Västra Götaland between December 2018 and January 2020. At study start, there were 3123 AEDs in Stockholm and 3195 in Västra Götaland and 24 493 volunteer responders in Stockholm and 19 117 in Västra Götaland. All OHCAs in which the volunteer responder system was activated by dispatchers were included. Excluded were patients with no OHCAs, those with OHCAs not treated by the emergency medical services, and those with OHCAs witnessed by the emergency medical services.<br /><b>Interventions</b><br />Volunteer responders were alerted through the volunteer responder system smartphone application and received map-aided instructions to retrieve nearest available public AEDs on their way to the OHCAs. The control arm included volunteer responders who were instructed to go directly to the OHCAs to perform CPR.<br /><b>Main outcomes and measures</b><br />Overall bystander AED attachment, including those attached by volunteer responders and lay volunteers who did not use the smartphone application.<br /><b>Results</b><br />Volunteer responders were activated for 947 patients with OHCAs. Of those, 461 were randomized to the intervention group (median [IQR] age of patients, 73 [61-81] years; 295 male patients [65.3%]) and 486 were randomized to the control group (median [IQR] age of patients, 73 [63-82] years; 312 male patients [65.3%]). Primary outcome of AED attachment occurred in 61 patients (13.2%) in the intervention arm vs 46 patients (9.5%) in the control arm (difference, 3.8% [95% CI, -0.3% to 7.9%]; P = .08). The majority of AEDs were attached by lay volunteers who were not using the smartphone application (37 in intervention arm, 28 in control). There were no significant differences in secondary outcomes. Among the volunteer responders using the application, crossover was 11% and compliance to instructions was 31%. Volunteer responders attached 38% (41 of 107) of all AEDs and provided 45% (16 of 36) of all defibrillations and 43% (293 of 666) of all CPR.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, smartphone dispatch of volunteer responders to OHCAs to retrieve nearby AEDs vs instructions to directly perform CPR did not significantly increase volunteer AED use. High baseline AED attachement rate and crossover may explain why the difference was not significant.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT02992873.<br /><br /><br /><br /><small>JAMA Cardiol: 30 Nov 2022; epub ahead of print</small></div>
Berglund E, Hollenberg J, Jonsson M, Svensson L, ... Riva G, Ringh M
JAMA Cardiol: 30 Nov 2022; epub ahead of print | PMID: 36449309
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<div><h4>Effect of Nudges to Clinicians, Patients, or Both to Increase Statin Prescribing: A Cluster Randomized Clinical Trial.</h4><i>Adusumalli S, Kanter GP, Small DS, Asch DA, ... Snider CK, Patel MS</i><br /><b>Importance</b><br />Statins reduce the risk of major adverse cardiovascular events, but less than one-half of individuals in America who meet guideline criteria for a statin are actively prescribed this medication.<br /><b>Objective</b><br />To evaluate whether nudges to clinicians, patients, or both increase initiation of statin prescribing during primary care visits.<br /><b>Design, setting, and participants</b><br />This cluster randomized clinical trial evaluated statin prescribing of 158 clinicians from 28 primary care practices including 4131 patients. The design included a 12-month preintervention period and a 6-month intervention period between October 19, 2019, and April 18, 2021.<br /><b>Interventions</b><br />The usual care group received no interventions. The clinician nudge combined an active choice prompt in the electronic health record during the patient visit and monthly feedback on prescribing patterns compared with peers. The patient nudge was an interactive text message delivered 4 days before the visit. The combined nudge included the clinician and patient nudges.<br /><b>Main outcomes and measures</b><br />The primary outcome was initiation of a statin prescription during the visit.<br /><b>Results</b><br />The sample comprised 4131 patients with a mean (SD) age of 65.5 (10.5) years; 2120 (51.3%) were male; 1210 (29.3%) were Black, 106 (2.6%) were Hispanic, 2732 (66.1%) were White, and 83 (2.0%) were of other race or ethnicity, and 933 (22.6%) had atherosclerotic cardiovascular disease. In unadjusted analyses during the preintervention period, statins were prescribed to 5.6% of patients (105 of 1876) in the usual care group, 4.8% (97 of 2022) in the patient nudge group, 6.0% (104 of 1723) in the clinician nudge group, and 4.7% (82 of 1752) in the combined group. During the intervention, statins were prescribed to 7.3% of patients (75 of 1032) in the usual care group, 8.5% (100 of 1181) in the patient nudge group, 13.0% (128 of 981) in the clinician nudge arm, and 15.5% (145 of 937) in the combined group. In the main adjusted analyses relative to usual care, the clinician nudge significantly increased statin prescribing alone (5.5 percentage points; 95% CI, 3.4 to 7.8 percentage points; P = .01) and when combined with the patient nudge (7.2 percentage points; 95% CI, 5.1 to 9.1 percentage points; P = .001). The patient nudge alone did not change statin prescribing relative to usual care (0.9 percentage points; 95% CI, -0.8 to 2.5 percentage points; P = .32).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Nudges to clinicians with and without a patient nudge significantly increased initiation of a statin prescription during primary care visits. The patient nudge alone was not effective.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT04307472.<br /><br /><br /><br /><small>JAMA Cardiol: 30 Nov 2022; epub ahead of print</small></div>
Adusumalli S, Kanter GP, Small DS, Asch DA, ... Snider CK, Patel MS
JAMA Cardiol: 30 Nov 2022; epub ahead of print | PMID: 36449275
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<div><h4>Statin-Associated Muscle Symptoms Among New Statin Users Randomly Assigned to Vitamin D or Placebo.</h4><i>Hlatky MA, Gonzalez PE, Manson JE, Buring JE, ... Bubes V, Stone NJ</i><br /><b>Importance</b><br />Statin-associated muscle symptoms (SAMS) are common and may lead to discontinuation of indicated statin therapy. Observational studies suggest that vitamin D therapy is associated with reduced statin intolerance, but no randomized studies have been reported.<br /><b>Objective</b><br />To test whether vitamin D supplementation was associated with prevention of SAMS and a reduction of statin discontinuation.<br /><b>Design, setting, and participants</b><br />Men 50 years or older and women 55 years or older, free of cancer and cardiovascular disease, were enrolled in a randomized, placebo-controlled, double-blind clinical trial of vitamin D supplementation. Participants who initiated statin therapy after randomization were surveyed in early 2016. The data were analyzed in early 2022.<br /><b>Interventions</b><br />Daily cholecalciferol (2000 international units) or placebo with assessment of statin prescriptions during follow-up.<br /><b>Main outcomes and measures</b><br />Muscle pain or discomfort lasting several days (primary outcome) and discontinuation of a statin due to SAMS (secondary outcome).<br /><b>Results</b><br />Statins were initiated by 1033 vitamin D-assigned participants and 1050 placebo-assigned participants; mean (SD) age was 66.8 (6.2) years and 49% were women. Over 4.8 years of follow-up, SAMS were reported by 317 participants (31%) assigned vitamin D and 325 assigned placebo (31%). The adjusted odds ratio (OR) was 0.97 (95% CI, 0.80-1.18; P = .78). Statins were discontinued by 137 participants (13%) assigned to vitamin D and 133 assigned to placebo (13%) with an adjusted OR of 1.04 (95% CI, 0.80-1.35; P = .78). These results were consistent across pretreatment 25-hydroxy vitamin D levels (interaction P value = .83). Among participants with levels less than 20 ng/mL, SAMS were reported by 28 of 85 vitamin D-assigned participants (33%) and 33 of 95 placebo-assigned participants (35%). For those with levels less than 30 ng/ml, SAMS were reported by 88 of 330 vitamin-D assigned participants (27%) and 96 of 323 of placebo-assigned participants (30%).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Vitamin D supplementation did not prevent SAMS or reduce statin discontinuation. These results were consistent across pretreatment 25-hydroxy vitamin D levels.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT01169259.<br /><br /><br /><br /><small>JAMA Cardiol: 23 Nov 2022; epub ahead of print</small></div>
Hlatky MA, Gonzalez PE, Manson JE, Buring JE, ... Bubes V, Stone NJ
JAMA Cardiol: 23 Nov 2022; epub ahead of print | PMID: 36416841
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<div><h4>Knowledge of Genome Sequencing and Trust in Medical Researchers Among Patients of Different Racial and Ethnic Groups With Idiopathic Dilated Cardiomyopathy.</h4><i>Ni H, Jordan E, Cao J, Kinnamon DD, ... Wang J, Hershberger RE</i><br /><b>Importance</b><br />Cardiovascular disease contributes outsized mortality in patients from underrepresented racial and ethnic groups. Understanding levels of trust in medical researchers and knowledge of genome sequencing may help identify barriers to research participation and develop strategies to educate patients about the role of genetics in cardiovascular disease.<br /><b>Objective</b><br />To assess racial and ethnic differences in trust in medical researchers and genome-sequencing knowledge among patients with idiopathic dilated cardiomyopathy and determine the association between trust in medical researchers and genome-sequencing knowledge.<br /><b>Design, setting, and participants</b><br />This cross-sectional study conducted by a consortium of 25 US heart failure programs included patients with idiopathic dilated cardiomyopathy defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes. Enrollment occurred from June 7, 2016, to March 15, 2020.<br /><b>Main outcomes and measures</b><br />Percent distributions, means, and associations of genome-sequencing knowledge scores and research trust scores for Hispanic, non-Hispanic Black (hereafter referred to as Black), and non-Hispanic White participants (hereafter referred to as White).<br /><b>Results</b><br />Among 1121 participants, mean (SD) age was 51.6 (13.6) years with 41.4% Black, 8.5% Hispanic, and 43.4% female. After accounting for site effects, the level of genome-sequencing knowledge was lower in Hispanic and Black participants compared with White participants (mean score difference, -2.6; 95% CI, -3.9 to -1.2 and mean score difference, -2.9; 95% CI, -3.6 to -2.2, respectively). The level of trust in researchers was lowest in Black participants (mean score, 27.7), followed by Hispanic participants (mean score, 29.4) and White participants (mean score, 33.9). Racial and ethnic differences remained after adjusting for education, age at enrollment, duration of dilated cardiomyopathy, and health status. A higher level of trust was associated with a higher level of genome-sequencing knowledge within different racial and ethnic groups.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this cross-sectional study, large racial and ethnic differences in levels of genome-sequencing knowledge and trust in medical researchers were observed among patients with dilated cardiomyopathy. Findings from this study can inform future studies that aim to enhance the uptake of genomic knowledge and level of trust in medical researchers.<br /><br /><br /><br /><small>JAMA Cardiol: 16 Nov 2022; epub ahead of print</small></div>
Ni H, Jordan E, Cao J, Kinnamon DD, ... Wang J, Hershberger RE
JAMA Cardiol: 16 Nov 2022; epub ahead of print | PMID: 36383367
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<div><h4>Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation: Prespecified Analysis at 6 Months of the RADIANCE-HTN TRIO Randomized Clinical Trial.</h4><i>Azizi M, Mahfoud F, Weber MA, Sharp ASP, ... Kirtane AJ, RADIANCE-HTN Investigators</i><br /><b>Importance</b><br />Although early trials of endovascular renal denervation (RDN) for patients with resistant hypertension (RHTN) reported inconsistent results, ultrasound RDN (uRDN) was found to decrease blood pressure (BP) vs sham at 2 months in patients with RHTN taking stable background medications in the Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN TRIO) trial.<br /><b>Objectives</b><br />To report the prespecified analysis of the persistence of the BP effects and safety of uRDN vs sham at 6 months in conjunction with escalating antihypertensive medications.<br /><b>Design, setting, and participants</b><br />This randomized, sham-controlled, clinical trial with outcome assessors and patients blinded to treatment assignment, enrolled patients from March 11, 2016, to March 13, 2020. This was an international, multicenter study conducted in the US and Europe. Participants with daytime ambulatory BP of 135/85 mm Hg or higher after 4 weeks of single-pill triple-combination treatment (angiotensin-receptor blocker, calcium channel blocker, and thiazide diuretic) with estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m2 or greater were randomly assigned to uRDN or sham with medications unchanged through 2 months. From 2 to 5 months, if monthly home BP was 135/85 mm Hg or higher, standardized stepped-care antihypertensive treatment starting with aldosterone antagonists was initiated under blinding to treatment assignment.<br /><b>Interventions</b><br />uRDN vs sham procedure in conjunction with added medications to target BP control.<br /><b>Main outcomes and measures</b><br />Six-month change in medications, change in daytime ambulatory systolic BP, change in home systolic BP adjusted for baseline BP and medications, and safety.<br /><b>Results</b><br />A total of 65 of 69 participants in the uRDN group and 64 of 67 participants in the sham group (mean [SD] age, 52.4 [8.3] years; 104 male [80.6%]) with a mean (SD) eGFR of 81.5 (22.8) mL/min/1.73 m2 had 6-month daytime ambulatory BP measurements. Fewer medications were added in the uRDN group (mean [SD], 0.7 [1.0] medications) vs sham (mean [SD], 1.1 [1.1] medications; P = .045) and fewer patients in the uRDN group received aldosterone antagonists at 6 months (26 of 65 [40.0%] vs 39 of 64 [60.9%]; P = .02). Despite less intensive standardized stepped-care antihypertensive treatment, mean (SD) daytime ambulatory BP at 6 months was 138.3 (15.1) mm Hg with uRDN vs 139.0 (14.3) mm Hg with sham (additional decreases of -2.4 [16.6] vs -7.0 [16.7] mm Hg from month 2, respectively), whereas home SBP was lowered to a greater extent with uRDN by 4.3 mm Hg (95% CI, 0.5-8.1 mm Hg; P = .03) in a mixed model adjusting for baseline and number of medications. Adverse events were infrequent and similar between groups.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, in patients with RHTN initially randomly assigned to uRDN or a sham procedure and who had persistent elevation of BP at 2 months after the procedure, standardized stepped-care antihypertensive treatment escalation resulted in similar BP reduction in both groups at 6 months, with fewer additional medications required in the uRDN group.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT02649426.<br /><br /><br /><br /><small>JAMA Cardiol: 09 Nov 2022; epub ahead of print</small></div>
Azizi M, Mahfoud F, Weber MA, Sharp ASP, ... Kirtane AJ, RADIANCE-HTN Investigators
JAMA Cardiol: 09 Nov 2022; epub ahead of print | PMID: 36350593
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<div><h4>Results of a Remotely Delivered Hypertension and Lipid Program in More Than 10 000 Patients Across a Diverse Health Care Network.</h4><i>Blood AJ, Cannon CP, Gordon WJ, Mailly C, ... Plutzky J, Scirica BM</i><br /><b>Importance</b><br />Blood pressure (BP) and cholesterol control remain challenging. Remote care can deliver more effective care outside of traditional clinician-patient settings but scaling and ensuring access to care among diverse populations remains elusive.<br /><b>Objective</b><br />To implement and evaluate a remote hypertension and cholesterol management program across a diverse health care network.<br /><b>Design, setting, and participants</b><br />Between January 2018 and July 2021, 20 454 patients in a large integrated health network were screened; 18 444 were approached, and 10 803 were enrolled in a comprehensive remote hypertension and cholesterol program (3658 patients with hypertension, 8103 patients with cholesterol, and 958 patients with both). A total of 1266 patients requested education only without medication titration. Enrolled patients received education, home BP device integration, and medication titration. Nonlicensed navigators and pharmacists, supported by cardiovascular clinicians, coordinated care using standardized algorithms, task management and automation software, and omnichannel communication. BP and laboratory test results were actively monitored.<br /><b>Main outcomes and measures</b><br />Changes in BP and low-density lipoprotein cholesterol (LDL-C).<br /><b>Results</b><br />The mean (SD) age among 10 803 patients was 65 (11.4) years; 6009 participants (56%) were female; 1321 (12%) identified as Black, 1190 (11%) as Hispanic, 7758 (72%) as White, and 1727 (16%) as another or multiple races (including American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, unknown, other, and declined to respond; consolidated owing to small numbers); and 142 (11%) reported a preferred language other than English. A total of 424 482 BP readings and 139 263 laboratory reports were collected. In the hypertension program, the mean (SD) office BP prior to enrollment was 150/83 (18/10) mm Hg, and the mean (SD) home BP was 145/83 (20/12) mm Hg. For those engaged in remote medication management, the mean (SD) clinic BP 6 and 12 months after enrollment decreased by 8.7/3.8 (21.4/12.4) and 9.7/5.2 (22.2/12.6) mm Hg, respectively. In the education-only cohort, BP changed by a mean (SD) -1.5/-0.7 (23.0/11.1) and by +0.2/-1.9 (30.3/11.2) mm Hg, respectively (P < .001 for between cohort difference). In the lipids program, patients in remote medication management experienced a reduction in LDL-C by a mean (SD) 35.4 (43.1) and 37.5 (43.9) mg/dL at 6 and 12 months, respectively, while the education-only cohort experienced a mean (SD) reduction in LDL-C of 9.3 (34.3) and 10.2 (35.5) mg/dL at 6 and 12 months, respectively (P < .001). Similar rates of enrollment and reductions in BP and lipids were observed across different racial, ethnic, and primary language groups.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />The results of this study indicate that a standardized remote BP and cholesterol management program may help optimize guideline-directed therapy at scale, reduce cardiovascular risk, and minimize the need for in-person visits among diverse populations.<br /><br /><br /><br /><small>JAMA Cardiol: 09 Nov 2022; epub ahead of print</small></div>
Blood AJ, Cannon CP, Gordon WJ, Mailly C, ... Plutzky J, Scirica BM
JAMA Cardiol: 09 Nov 2022; epub ahead of print | PMID: 36350612
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<div><h4>Population-Level Implications of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure With Preserved Ejection Fraction in the US.</h4><i>Talha KM, Butler J, Greene SJ, Aggarwal R, ... Vaduganathan M, Fonarow GC</i><br /><b>Importance</b><br />The expansion of sodium-glucose cotransporter-2 (SGLT-2) inhibitor use in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) more than 40% following the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) and the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trials have major implications in the US.<br /><b>Objective</b><br />To quantify the estimated US population-level impact of reducing worsening HF events with SGLT-2 inhibitors in individuals with LVEF more than 40%.<br /><b>Design, setting, and participants</b><br />This decision analytical model study used self-reported HF data from the National Health and Nutritional Examination Survey from 2015 to 2018, which was weighted across the entire US population and subsequently mapped onto newly eligible LVEF distributions from the Get With The Guidelines-Heart Failure registry. All patients older than 18 years with HF from the National Health and Nutritional Examination Survey were grouped into the following categories: all LVEF and LVEF more than 40%. Numbers needed to treat estimations over 3 years were obtained for outcome measures from the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction), EMPEROR-Preserved, DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), and DELIVER trials.<br /><b>Main outcomes and measures</b><br />Worsening HF events (unplanned HF hospitalizations, urgent HF visits requiring intravenous therapy, or cardiovascular death).<br /><b>Results</b><br />A projected 4 794 524 (95% CI, 3 997 363-5 591 684) adults (57% male; 67% White; mean age, 66 years) with HF would be eligible for SGLT-2 inhibitors. Of this total population, 2 619 248 (95% CI, 2 183 759-3 054 737) would be estimated as newly eligible with LVEF more than 40%. Based on estimates from the EMPEROR-Reduced/EMPEROR-Preserved and DAPA-HF/DELIVER trials, a projected 624 247 (95% CI, 520 457-728 037) to 627 124 (95% CI, 522 855-731 392) worsening HF events could be prevented across the LVEF spectrum with SGLT-2 inhibitors over 3 years, of which 232 589 (95% CI, 193 918-271 260) to 282 879 (95% CI, 235 846-329 912) events could be prevented in individuals with LVEF more than 40%. Moreover, an estimated 468 904 (95% CI, 390 942-546 867) to 499 110 (95% CI, 416 125-582 094) total HF hospitalizations could be prevented across the LVEF spectrum, of which 172 870 (95% CI, 144 128-201 613) to 231 018 (95% CI, 192 608-269 428) could be prevented in individuals with LVEF more than 40%.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In addition to the proven benefit in HF with LVEF of 40% and less, optimal implementation of SGLT-2 inhibitor therapy for HF with LVEF more than 40% can potentially prevent/postpone an additional approximately 250 000 worsening HF events over 3 years in the US.<br /><br /><br /><br /><small>JAMA Cardiol: 05 Nov 2022; epub ahead of print</small></div>
Talha KM, Butler J, Greene SJ, Aggarwal R, ... Vaduganathan M, Fonarow GC
JAMA Cardiol: 05 Nov 2022; epub ahead of print | PMID: 36334258
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<div><h4>Initial Thoracic Endovascular Aortic Repair vs Medical Therapy for Acute Uncomplicated Type B Aortic Dissection.</h4><i>Weissler EH, Osazuwa-Peters OL, Greiner MA, Hardy NC, ... Patel MR, Vemulapalli S</i><br /><b>Importance</b><br />Thoracic endovascular aortic repair (TEVAR) has increasingly been used for uncomplicated type B aortic dissection (uTBAD) despite limited supporting data.<br /><b>Objective</b><br />To assess whether initial TEVAR following uTBAD is associated with reduced mortality or morbidity compared with medical therapy alone.<br /><b>Design, setting, and participants</b><br />This cohort study included Centers for Medicare & Medicaid Services inpatient claims data for adults aged 65 years or older with index admissions for acute uTBAD from January 1, 2011, to December 31, 2018, with follow-up available through December 31, 2019.<br /><b>Exposures</b><br />Initial TEVAR was defined as TEVAR within 30 days of admission for acute uTBAD.<br /><b>Main outcomes and measures</b><br />Outcomes included all-cause mortality, cardiovascular hospitalizations, aorta-related and repeated aorta-related hospitalizations, and aortic interventions associated with initial TEVAR vs medical therapy. Propensity score inverse probability weighting was used.<br /><b>Results</b><br />Of 7105 patients with eligible index admissions for acute uTBAD, 1140 (16.0%) underwent initial TEVAR (623 [54.6%] female; median age, 74 years [IQR, 68-80 years]) and 5965 (84.0%) did not undergo TEVAR (3344 [56.1%] female; median age, 76 years [IQR, 69-83 years]). Receipt of TEVAR was associated with region (vs South; Midwest: adjusted odds ratio [aOR], 0.66 [95% CI, 0.53-0.81]; P < .001; Northeast: aOR, 0.63 [95% CI, 0.50-0.79]; P < .001), Medicaid dual eligibility (aOR, 0.76; 95% CI, 0.63-0.91; P = .003), hypertension (aOR, 1.26; 95% CI, 1.03-1.54; P = .03), peripheral vascular disease (aOR, 1.24; 95% CI, 1.02-1.49; P = .03), and year of admission (2012, 2013, 2014, and 2015 were associated with greater odds of TEVAR compared with 2011). After inverse probability weighting, mortality was similar for the 2 strategies up to 5 years (hazard ratio [HR], 0.95; 95% CI, 0.85-1.06), as were aorta-related hospitalizations (HR, 1.12; 95% CI, 0.99-1.27), aortic interventions (HR, 1.01; 95% CI, 0.84-1.20), and cardiovascular hospitalizations (HR, 1.05; 95% CI, 0.93-1.20). In a sensitivity analysis that included deaths within the first 30 days, initial TEVAR was associated with lower mortality over a period of 1 year (adjusted HR [aHR], 0.86; 95% CI, 0.75-0.99; P = .03), 2 years (aHR, 0.85; 95% CI, 0.75-0.96; P = .008), and 5 years (aHR, 0.87; 95% CI, 0.80-0.96; P = .004).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, 16.0% of patients underwent initial TEVAR within 30 days of uTBAD, and receipt of initial TEVAR was associated with hypertension, peripheral vascular disease, region, Medicaid dual eligibility, and year of admission. Initial TEVAR was not associated with improved mortality or reduced hospitalizations or aortic interventions over a period of 5 years, but in a sensitivity analysis that included deaths within the first 30 days, initial TEVAR was associated with lower mortality. These findings, along with cost-effectiveness and quality of life, should be assessed in a prospective trial in the US population.<br /><br /><br /><br /><small>JAMA Cardiol: 05 Nov 2022; epub ahead of print</small></div>
Weissler EH, Osazuwa-Peters OL, Greiner MA, Hardy NC, ... Patel MR, Vemulapalli S
JAMA Cardiol: 05 Nov 2022; epub ahead of print | PMID: 36334259
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<div><h4>Dapagliflozin and Kidney Outcomes in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Analysis of the DELIVER Randomized Clinical Trial.</h4><i>Mc Causland FR, Claggett BL, Vaduganathan M, Desai AS, ... McMurray JJV, Solomon SD</i><br /><b>Importance</b><br />Sodium-glucose cotransporter 2 inhibitors are known to reduce heart failure events and slow progression of kidney disease among patients with heart failure and a reduced ejection fraction.<br /><b>Objective</b><br />To determine the effect of dapagliflozin on cardiovascular and kidney outcomes and the influence of baseline kidney disease among patients with heart failure and a mildly reduced or preserved ejection fraction enrolled in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial.<br /><b>Design, setting, and participants</b><br />This was a prespecified analysis conducted from July 1 to September 18, 2022 of the DELIVER randomized clinical trial. This was an international, multicenter trial including patients with ejection fraction greater than 40% and estimated glomerular filtration rate (eGFR) of 25 mL/min/1.73 m2 or higher.<br /><b>Interventions</b><br />Dapagliflozin, 10 mg, per day or placebo.<br /><b>Main outcomes and measures</b><br />Outcomes assessed were whether baseline kidney function modified the treatment effect on the primary outcome (cardiovascular death or worsening heart failure). Also examined was the treatment effect on the prespecified outcomes of eGFR slope and a post hoc composite kidney outcome (first ≥50% decline in eGFR from baseline; first eGFR <15 mL/min/1.73 m2; end-stage kidney disease; death from kidney causes).<br /><b>Results</b><br />A total of 6262 patients (mean [SD] age, 72 [10] years; 3516 male [56%]) had mean (SD) eGFR measurements available: 61 (19) mL/min/1.73 m2; 3070 patients (49%) had an eGFR less than 60 mL/min/1.73 m2. The effect of dapagliflozin on the primary outcome was not influenced by baseline eGFR category (eGFR ≥60 mL/min/1.73 m2: hazard ratio [HR], 0.84; 95% CI, 0.70-1.00; eGFR 45-<60 mL/min/1.73 m2: HR, 0.68; 95% CI, 0.54-0.87; eGFR <45 mL/min/1.73 m2: HR, 0.93; 95% CI, 0.76-1.14; P for interaction = .16). Over a median (IQR) follow-up of 2.3 (1.7-2.8) years, the overall incidence rate of the kidney composite outcome was low (1.1 events per 100 patient-years) and was not affected by treatment with dapagliflozin (HR, 1.08; 95% CI, 0.79-1.49). However, dapagliflozin attenuated the decline in eGFR from baseline (difference, 0.5; 95% CI, 0.1-0.9 mL/min/1.73 m2 per year; P = .01) and from month 1 to 36 (difference, 1.4; 95% CI, 1.0-1.8) mL/min/1.73 m2 per year; P < .001).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Results of this prespecified analysis showed that baseline kidney function did not modify the benefit of dapagliflozin in patients with heart failure and a mildly reduced or preserved ejection fraction. Dapagliflozin did not significantly reduce the frequency of the kidney composite outcome, although the overall event rate was low. However, dapagliflozin slowed the rate of decline in eGFR compared with placebo.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03619213.<br /><br /><br /><br /><small>JAMA Cardiol: 03 Nov 2022; epub ahead of print</small></div>
Mc Causland FR, Claggett BL, Vaduganathan M, Desai AS, ... McMurray JJV, Solomon SD
JAMA Cardiol: 03 Nov 2022; epub ahead of print | PMID: 36326604
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<div><h4>Use of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagonlike Peptide-1 Receptor Agonists in Patients With Diabetes and Cardiovascular Disease in Community Practice.</h4><i>Nanna MG, Kolkailah AA, Page C, Peterson ED, Navar AM</i><br /><b>Importance</b><br />Recent national guidelines recommend sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD); yet, there are limited data on the use of these agents in contemporary community practice.<br /><b>Objective</b><br />To evaluate the use of SGLT2i and GLP-1 RA in adults with T2D and ASCVD across a diverse sample of health care systems in the US.<br /><b>Design, setting, and participants</b><br />This multicenter, retrospective cohort study used electronic health record data from 88 US health care systems participating in Cerner Real World Data between January 2018 to March 2021. Adults with ASCVD and T2D taking at least 1 glucose-lowering medication, had end-stage kidney disease, or had stage 5 chronic kidney disease were excluded.<br /><b>Main outcomes and measures</b><br />Treatment with SGLT2i or GLP-1 RA.<br /><b>Results</b><br />A total of 321 304 patients were identified with T2D and ASCVD ASCVD (130 280 female [40.5%]; median [IQR] age, 70.9 [62.9-78.0] years) who were potentially eligible for SGLT2i and/or GLP-1 RA, including 37 754 Black individuals (11.8%), 51 522 Hispanic individuals (16.0%), and 256 008 White individuals (11.8%). From January 2018 to March 2021, the use of SGLT2i increased from 5.8% (11 285 of 194 264) to 12.9% (11 058 of 85 956), GLP-1 RA increased from 6.9% (13 402 of 194 264) to 13.8% (11 901 of 85 956), and use of either agent increased from 11.4% (22 069 of 194 264) to 23.2% (19 909 of 85 956). Those taking an SGLT2i or GLP-1 RA were younger, less frequently hospitalized in the year prior, and more likely to be taking additional secondary prevention medications. Treated and nontreated populations were similar in terms of race, ethnicity, and outpatient health care utilization. Sulfonylureas and dipeptidyl peptidase 4 inhibitors remained more commonly used than SGLT2i or GLP-1 RA through 2021.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, uptake of SGLT2i and GLP-1 RA in adults with T2D and ASCVD increased modestly after guideline recommendations, although less than a quarter of persons with ASCVD and T2D receiving medical therapy were taking either. Further efforts are necessary to maximize the potential population benefit of these therapies in this high-risk population.<br /><br /><br /><br /><small>JAMA Cardiol: 02 Nov 2022; epub ahead of print</small></div>
Nanna MG, Kolkailah AA, Page C, Peterson ED, Navar AM
JAMA Cardiol: 02 Nov 2022; epub ahead of print | PMID: 36322056
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<div><h4>Concordance Between Patient-Reported Health Data and Electronic Health Data in the ADAPTABLE Trial.</h4><i>O\'Brien EC, Mulder H, Jones WS, Hammill BG, ... Hernandez AF, Curtis LH</i><br /><b>Importance</b><br />Patient-reported health data can facilitate clinical event capture in pragmatic clinical trials. However, few data are available on the fitness for use of patient-reported data in large-scale health research.<br /><b>Objective</b><br />To evaluate the concordance of a set of variables reported by patients and available in the electronic health record as part of a pragmatic clinical trial.<br /><b>Design, setting, and participants</b><br />Data from ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic clinical trial, were used in a concordance substudy of a comparative effectiveness research trial. The trial randomized 15 076 patients with existing atherosclerotic cardiovascular disease in a 1:1 ratio to low- or high-dose aspirin from April 2016 through June 30, 2019.<br /><b>Main outcomes and measures</b><br />Concordance of data was evaluated from 4 domains (demographic characteristics, encounters, diagnoses, and procedures) present in 2 data sources: patient-reported data captured through an online portal and data from electronic sources (electronic health record data). Overall agreement, sensitivity, specificity, positive predictive value, negative predictive value, and κ statistics with 95% CIs were calculated using patient report as the criterion standard for demographic characteristics and the electronic health record as the criterion standard for clinical outcomes.<br /><b>Results</b><br />Of 15 076 patients with complete information, the median age was 67.6 years (range, 21-99 years), and 68.7% were male. With the use of patient-reported data as the criterion standard, agreement (κ) was high for Black and White race and ethnicity but only moderate for current smoking status. Electronic health record data were highly specific (99.6%) but less sensitive (82.5%) for Hispanic ethnicity. Compared with electronic health record data, patient report of clinical end points had low sensitivity for myocardial infarction (33.0%), stroke (34.2%), and major bleeding (36.6%). Positive predictive value was similarly low for myocardial infarction (40.7%), stroke (38.8%), and major bleeding (21.9%). Coronary revascularization was the most concordant event by data source, with only moderate agreement (κ = 0.54) and positive predictive value. Agreement metrics varied by site for all demographic characteristics and several clinical events.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In a concordance substudy of a large, pragmatic comparative effectiveness research trial, sensitivity and chance-corrected agreement of patient-reported data captured through an online portal for cardiovascular events were low to moderate. Findings suggest that additional work is needed to optimize integration of patient-reported health data into pragmatic research studies.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT02697916.<br /><br /><br /><br /><small>JAMA Cardiol: 02 Nov 2022; epub ahead of print</small></div>
O'Brien EC, Mulder H, Jones WS, Hammill BG, ... Hernandez AF, Curtis LH
JAMA Cardiol: 02 Nov 2022; epub ahead of print | PMID: 36322059
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This program is still in alpha version.