Stroke; A Journal Of Cerebral Circulation[JOURNAL]
Sun
200 papers
Energetic Basis for Exercise-Induced Pulmonary Congestion in Heart Failure With Preserved Ejection Fraction.
Burrage MK, Hundertmark M, Valkovič L … +8 more , Watson WD, Rayner J, Sabharwal N, Ferreira VM, Neubauer S, Miller JJ, Rider OJ, Lewis AJM
Circulation · 2021 Nov · PMID 34743560 · Full text
BACKGROUND: Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an...
BACKGROUND: Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an abnormal cardiac energetic state underpins this process. METHODS: We recruited patients across the spectrum of diastolic dysfunction and HFpEF (controls, n=11; type 2 diabetes, n=9; HFpEF, n=14; and severe diastolic dysfunction attributable to cardiac amyloidosis, n=9). Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to ATP ratio. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging and echocardiography and lung water using magnetic resonance proton density mapping. Studies were performed at rest and during submaximal exercise using a magnetic resonance imaging ergometer. RESULTS: Paralleling the stepwise decline in diastolic function across the groups (E/e' ratio; <0.001) was an increase in NT-proBNP (N-terminal pro-brain natriuretic peptide; <0.001) and a reduction in phosphocreatine/ATP ratio (control, 2.15 [2.09, 2.29]; type 2 diabetes, 1.71 [1.61, 1.91]; HFpEF, 1.66 [1.44, 1.89]; cardiac amyloidosis, 1.30 [1.16, 1.53]; <0.001). During 20-W exercise, lower left ventricular diastolic filling rates (r=0.58; <0.001), lower left ventricular diastolic reserve (r=0.55; <0.001), left atrial dilatation (r=-0.52; <0.001), lower right ventricular contractile reserve (right ventricular ejection fraction change, r=0.57; <0.001), and right atrial dilation (r=-0.71; <0.001) were all linked to lower phosphocreatine/ATP ratio. Along with these changes, pulmonary proton density mapping revealed transient pulmonary congestion in patients with HFpEF (+4.4% [0.5, 6.4]; =0.002) and cardiac amyloidosis (+6.4% [3.3, 10.0]; =0.004), which was not seen in healthy controls (-0.1% [-1.9, 2.1]; =0.89) or type 2 diabetes without HFpEF (+0.8% [-1.7, 1.9]; =0.82). The development of exercise-induced pulmonary congestion was associated with lower phosphocreatine/ATP ratio (r=-0.43; =0.004). CONCLUSIONS: A gradient of myocardial energetic deficit exists across the spectrum of HFpEF. Even at low workload, this energetic deficit is related to markedly abnormal exercise responses in all 4 cardiac chambers, which is associated with detectable pulmonary congestion. The findings support an energetic basis for transient pulmonary congestion in HFpEF.
Prognostic Value of Elevated Levels of Plasma N-Acetylneuraminic Acid in Patients With Heart Failure.
Li C, Zhao M, Xiao L … +21 more , Wei H, Wen Z, Hu D, Yu B, Sun Y, Gao J, Shen X, Zhang Q, Cao H, Huang J, Huang W, Li K, Huang M, Ni L, Yu T, Ji L, Xu Y, Liu G, Konerman MC, Zheng L, Wen Wang D
Circ Heart Fail · 2021 Nov · PMID 34711067 · Publisher ↗
BACKGROUND: Cardiac sialylation is involved in a variety of physiological processes in the heart. Altered sialylation has been implicated in heart failure (HF) mice. However, its role in patients with HF is unclear, and...
BACKGROUND: Cardiac sialylation is involved in a variety of physiological processes in the heart. Altered sialylation has been implicated in heart failure (HF) mice. However, its role in patients with HF is unclear, and the potential effect of modulation of cardiac sialylation is worth exploring. METHODS: We first assessed the association between plasma N-acetylneuraminic acid levels and the incidence of adverse cardiovascular events in patients with HF over a median follow-up period of 2 years. Next, immunoblot analysis and lectin histochemistry were performed in cardiac tissue to determine the expression levels of neuraminidases and the extent of cardiac desialylation. Finally, the therapeutic impact of a neuraminidase inhibitor was evaluated in animal models of HF. RESULTS: Among 1699 patients with HF, 464 (27%) died of cardiovascular-related deaths or underwent heart transplantation. We found that the elevated plasma N-acetylneuraminic acid level was independently associated with a higher risk of incident cardiovascular death and heart transplantation (third tertile adjusted hazard ratio, 2.11 [95% CI, 1.67-2.66], <0.001). In addition, in cardiac tissues from patients with HF, neuraminidase expression was upregulated, accompanied by desialylation. Treatment with oseltamivir, a neuraminidase inhibitor, in HF mice infused with isoproterenol and angiotensin II significantly inhibited desialylation and ameliorated cardiac dysfunction. CONCLUSIONS: This study uncovered a significant association between elevated plasma N-acetylneuraminic acid level and an increased risk of a poor clinical outcome in patients with HF. Our data support the notion that desialylation represents an important contributor to the progression of HF, and neuraminidase inhibition may be a potential therapeutic strategy for HF.
Predictors of Atrial Fibrillation Development in Patients With Embolic Stroke of Undetermined Source: An Analysis of the RE-SPECT ESUS Trial.
Bahit MC, Sacco RL, Easton JD … +13 more , Meyerhoff J, Cronin L, Kleine E, Grauer C, Brueckmann M, Diener HC, Lopes RD, Brainin M, Lyrer P, Wachter R, Segura T, Granger CB, RE-SPECT ESUS Steering Committee and Investigators
Circulation · 2021 Nov · PMID 34649459 · Publisher ↗
BACKGROUND: A proportion of patients with embolic stroke of undetermined source have silent atrial fibrillation (AF) or develop AF after the initial evaluation. Better understanding of the risk for development of AF is c...
BACKGROUND: A proportion of patients with embolic stroke of undetermined source have silent atrial fibrillation (AF) or develop AF after the initial evaluation. Better understanding of the risk for development of AF is critical to implement optimal monitoring strategies with the goal of preventing recurrent stroke attributable to underlying AF. The RE-SPECT ESUS trial (Randomized, Double-Blind Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) provides an opportunity to assess predictors for developing AF and associated recurrent stroke. METHODS: RE-SPECT ESUS was a randomized, controlled trial (564 sites, 42 countries) assessing dabigatran versus aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. Of 5390 patients enrolled and followed for a median of 19 months, 403 (7.5%) were found to develop AF reported as an adverse event or using cardiac monitoring per standard clinical care. Univariable and multivariable regression analyses were performed to define predictors of AF. RESULTS: In the multivariable model, older age (odds ratio for 10-year increase, 1.99 [95% CI, 1.78-2.23]; <0.001), hypertension (odds ratio, 1.36 [95% CI, 1.03-1.79]; =0.0304), diabetes (odds ratio, 0.74 [95% CI, 0.56-0.96]; =0.022), and body mass index (odds ratio for 5-U increase, 1.29 [95% CI, 1.16-1.43]; <0.001) were independent predictors of AF during the study. In a sensitivity analysis restricted to 1117 patients with baseline NT-proBNP (N-terminal prohormone of brain natriuretic peptide) measurements, only older age and higher NT-proBNP were significant independent predictors of AF. Performance of several published predictive models was assessed, including HAVOC (AF risk score based on hypertension, age ≥75 years, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, and coronary artery disease) and CHADS-VASc (stroke risk score based on congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, previous stroke, transient ischemic attack or thromboembolism [doubled], vascular disease, age 65 to 74 years, and sex category [female]) scores, and higher scores were associated with higher rates of developing AF. CONCLUSIONS: Besides age, the most important variable, several other factors, including hypertension, higher body mass index, and lack of diabetes, are independent predictors of AF after embolic stroke of undetermined source. When baseline NT-proBNP was available, only older age and elevation of this biomarker were predictive of subsequent AF. Understanding who is at higher risk of developing AF will assist in identifying patients who may benefit from more intense, long-term cardiac monitoring. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.
Loss of Mitochondrial Ca Uniporter Limits Inotropic Reserve and Provides Trigger and Substrate for Arrhythmias in Barth Syndrome Cardiomyopathy.
Bertero E, Nickel A, Kohlhaas M … +25 more , Hohl M, Sequeira V, Brune C, Schwemmlein J, Abeßer M, Schuh K, Kutschka I, Carlein C, Münker K, Atighetchi S, Müller A, Kazakov A, Kappl R, von der Malsburg K, van der Laan M, Schiuma AF, Böhm M, Laufs U, Hoth M, Rehling P, Kuhn M, Dudek J, von der Malsburg A, Prates Roma L, Maack C
Circulation · 2021 Nov · PMID 34648376 · Publisher ↗
BACKGROUND: Barth syndrome (BTHS) is caused by mutations of the gene encoding tafazzin, which catalyzes maturation of mitochondrial cardiolipin and often manifests with systolic dysfunction during early infancy. Beyond t...
BACKGROUND: Barth syndrome (BTHS) is caused by mutations of the gene encoding tafazzin, which catalyzes maturation of mitochondrial cardiolipin and often manifests with systolic dysfunction during early infancy. Beyond the first months of life, BTHS cardiomyopathy typically transitions to a phenotype of diastolic dysfunction with preserved ejection fraction, blunted contractile reserve during exercise, and arrhythmic vulnerability. Previous studies traced BTHS cardiomyopathy to mitochondrial formation of reactive oxygen species (ROS). Because mitochondrial function and ROS formation are regulated by excitation-contraction coupling, integrated analysis of mechano-energetic coupling is required to delineate the pathomechanisms of BTHS cardiomyopathy. METHODS: We analyzed cardiac function and structure in a mouse model with global knockdown of tafazzin (-KD) compared with wild-type littermates. Respiratory chain assembly and function, ROS emission, and Ca uptake were determined in isolated mitochondria. Excitation-contraction coupling was integrated with mitochondrial redox state, ROS, and Ca uptake in isolated, unloaded or preloaded cardiac myocytes, and cardiac hemodynamics analyzed in vivo. RESULTS: -KD mice develop heart failure with preserved ejection fraction (>50%) and age-dependent progression of diastolic dysfunction in the absence of fibrosis. Increased myofilament Ca affinity and slowed cross-bridge cycling caused diastolic dysfunction, in part, compensated by accelerated diastolic Ca decay through preactivated sarcoplasmic reticulum Ca-ATPase. deficiency provoked heart-specific loss of mitochondrial Ca uniporter protein that prevented Ca-induced activation of the Krebs cycle during β-adrenergic stimulation, oxidizing pyridine nucleotides and triggering arrhythmias in cardiac myocytes. In vivo, -KD mice displayed prolonged QRS duration as a substrate for arrhythmias, and a lack of inotropic response to β-adrenergic stimulation. Cellular arrhythmias and QRS prolongation, but not the defective inotropic reserve, were restored by inhibiting Ca export through the mitochondrial Na/Ca exchanger. All alterations occurred in the absence of excess mitochondrial ROS in vitro or in vivo. CONCLUSIONS: Downregulation of mitochondrial Ca uniporter, increased myofilament Ca affinity, and preactivated sarcoplasmic reticulum Ca-ATPase provoke mechano-energetic uncoupling that explains diastolic dysfunction and the lack of inotropic reserve in BTHS cardiomyopathy. Furthermore, defective mitochondrial Ca uptake provides a trigger and a substrate for ventricular arrhythmias. These insights can guide the ongoing search for a cure of this orphaned disease.
Associations of Medicaid Expansion With Access to Care, Severity, and Outcomes for Acute Ischemic Stroke.
McGee BT, Seagraves KB, Smith EE … +7 more , Xian Y, Zhang S, Alhanti B, Matsouaka RA, Reeves M, Schwamm LH, Fonarow GC
Circ Cardiovasc Qual Outcomes · 2021 Oct · PMID 34587752 · Publisher ↗
BACKGROUND: Multiple states have not expanded Medicaid under the Affordable Care Act, resulting in higher uninsured rates in states with high stroke burdens. This study aimed to evaluate the association of Medicaid expan...
BACKGROUND: Multiple states have not expanded Medicaid under the Affordable Care Act, resulting in higher uninsured rates in states with high stroke burdens. This study aimed to evaluate the association of Medicaid expansion with changes in health insurance coverage, severity of presentation, access to care, and outcomes among patients with acute ischemic stroke. METHODS: A retrospective, difference-in-differences analysis of Get With The Guidelines-Stroke registry data. The study population comprised first-time ischemic stroke admissions from 2012 to 2018 for patients aged 19 to 64 in 45 states (27 that expanded Medicaid and 18 that did not). A probable low-income cohort was defined based on having Medicaid, no insurance/self-pay, or undocumented insurance. Outcomes analyzed were indicators of health insurance status, stroke severity, use of emergency services, time to acute care, in-hospital mortality, receipt of rehabilitation, discharge disposition, and level of disability. RESULTS: In the starting population (N=342 765), Medicaid-covered stroke admissions rose from 12.2% to 18.1% in expansion states and from 10.0% to only 10.6% in nonexpansion states, while uninsured admissions declined from 15.0% to 6.7% in expansion states and from 24.0% to 19.2% in nonexpansion states. In the low-income cohort (N=95 086; 28% of starting population), Medicaid expansion was associated with increased odds of discharge to a skilled nursing facility (adjusted odds ratio, 1.33 [95% CI, 1.12-1.59]) and transfer to any rehabilitation facility among those eligible (adjusted odds ratio, 1.24 [95% CI, 1.08-1.41]) and lower odds of discharge home (adjusted odds ratio, 0.89 [95% CI, 0.80-0.98]). Expansion was not associated with any other outcomes. CONCLUSIONS: Medicaid expansion is associated with fewer uninsured hospitalizations for acute ischemic stroke and increased rehabilitation at skilled nursing facilities. More targeted interventions may be needed to improve other stroke outcomes in the low-income US population. Future research should evaluate the impact of health care reform on primary stroke prevention.
Clinical Characteristics and Outcomes of Adults With a History of Heart Failure Hospitalized for COVID-19.
Goyal P, Reshetnyak E, Khan S … +13 more , Musse M, Navi BB, Kim J, Allen LA, Banerjee S, Elkind MSV, Shah SJ, Yancy C, Michos ED, Devereux RB, Okin PM, Weinsaft JW, Safford MM
Circ Heart Fail · 2021 Sep · PMID 34517720 · Full text
BACKGROUND: It is important to understand the risk for in-hospital mortality of adults hospitalized with acute coronavirus disease 2019 (COVID-19) infection with a history of heart failure (HF). METHODS: We examined pati...
BACKGROUND: It is important to understand the risk for in-hospital mortality of adults hospitalized with acute coronavirus disease 2019 (COVID-19) infection with a history of heart failure (HF). METHODS: We examined patients hospitalized with COVID-19 infection from January 1, 2020 to July 22, 2020, from 88 centers across the US participating in the American Heart Association's COVID-19 Cardiovascular Disease registry. The primary exposure was history of HF and the primary outcome was in-hospital mortality. To examine the association between history of HF and in-hospital mortality, we conducted multivariable modified Poisson regression models that included sociodemographics and comorbid conditions. We also examined HF subtypes based on left ventricular ejection fraction in the prior year, when available. RESULTS: Among 8920 patients hospitalized with COVID-19, mean age was 61.4±17.5 years and 55.5% were men. History of HF was present in 979 (11%) patients. In-hospital mortality occurred in 31.6% of patients with history of HF, and 16.9% in patients without a history of HF. In a fully adjusted model, history of HF was associated with increased risk for in-hospital mortality (relative risk: 1.16 [95% CI, 1.03-1.30]). Among 335 patients with left ventricular ejection fraction, heart failure with reduced ejection fraction was significantly associated with in-hospital mortality in a fully adjusted model (heart failure with reduced ejection fraction relative risk: 1.40 [95% CI, 1.10-1.79]; heart failure with mid-range ejection fraction relative risk: 1.06 [95% CI, 0.65-1.73]; heart failure with preserved ejection fraction relative risk, 1.06 [95% CI, 0.84-1.33]). CONCLUSIONS: Risk for in-hospital mortality was substantial among adults with history of HF, in large part due to age and comorbid conditions. History of heart failure with reduced ejection fraction may confer especially elevated risk. This population thus merits prioritization for the COVID-19 vaccine.
Bleeding and Subsequent Cardiovascular Events and Death in Atrial Fibrillation With Stable Coronary Artery Disease: Insights From the AFIRE Trial.
Kaikita K, Yasuda S, Akao M … +9 more , Ako J, Matoba T, Nakamura M, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H
Circ Cardiovasc Interv · 2021 Nov · PMID 34474583 · Publisher ↗
BACKGROUND: Early bleeding after percutaneous coronary intervention is associated with increased risk of death and myocardial infarction; however, the association between bleeding and subsequent major adverse cardiac and...
BACKGROUND: Early bleeding after percutaneous coronary intervention is associated with increased risk of death and myocardial infarction; however, the association between bleeding and subsequent major adverse cardiac and cerebrovascular events (MACCE) remains unclear in patients with atrial fibrillation and stable coronary artery disease. We thus aimed to investigate this association. METHODS: The AFIRE trial (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) was a multicenter, open-label trial conducted in Japan. This post hoc analysis included 2215 patients with atrial fibrillation and stable coronary artery disease treated with rivaroxaban or rivaroxaban plus an antiplatelet agent. MACCE was defined as a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. The association of bleeding with subsequent MACCE risk was investigated using time-adjusted Cox multivariate analysis after adjusting for baseline characteristics and time from bleeding. Bleeding events were classified according to the International Society on Thrombosis and Haemostasis criteria. RESULTS: Among the 2215 patients, 386 (17.4%) had bleeding during follow-up, of whom 63 (16.3%) also experienced MACCE; MACCE incidence was higher in patients with bleeding than in those without (8.38% versus 4.20% per patient-year; hazard ratio, 2.01 [95% CI, 1.49-2.70]; <0.001). The proportion of patients with both bleeding and MACCE (developed after bleeding) was 73.0% (46 of 63); 27.0% (17 of 63) experienced MACCE before bleeding. Time-adjusted Cox multivariate analysis revealed a temporal association between major bleeding and subsequent MACCE, with particularly high MACCE risks within 30 days after major bleeding (hazard ratio, 7.81 [95% CI, 4.20-14.54]). CONCLUSIONS: In patients with atrial fibrillation and stable coronary artery disease, major bleeding was strongly associated with subsequent MACCE. Thus, it is important to prevent major bleeding to avoid cardiovascular events and death. Registration: URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000016612. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02642419. Graphic Abstract: A graphic abstract is available for this article.
Predictive Accuracy of a Clinical and Genetic Risk Model for Atrial Fibrillation.
Khurshid S, Mars N, Haggerty CM … +14 more , Huang Q, Weng LC, Hartzel DN, Regeneron Genetics Center, Lunetta KL, Ashburner JM, Anderson CD, Benjamin EJ, Salomaa V, Ellinor PT, Fornwalt BK, Ripatti S, Trinquart L, Lubitz SA
Circ Genom Precis Med · 2021 Oct · PMID 34463125 · Full text
BACKGROUND: Atrial fibrillation (AF) risk estimation using clinical factors with or without genetic information may identify AF screening candidates more accurately than the guideline-based age threshold of ≥65 years. ME...
BACKGROUND: Atrial fibrillation (AF) risk estimation using clinical factors with or without genetic information may identify AF screening candidates more accurately than the guideline-based age threshold of ≥65 years. METHODS: We analyzed 4 samples across the United States and Europe (derivation: UK Biobank; validation: FINRISK, Geisinger MyCode Initiative, and Framingham Heart Study). We estimated AF risk using the CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology AF) score and a combination of CHARGE-AF and a 1168-variant polygenic score (Predict-AF). We compared the utility of age, CHARGE-AF, and Predict-AF for predicting 5-year AF by quantifying discrimination and calibration. RESULTS: Among 543 093 individuals, 8940 developed AF within 5 years. In the validation sets, CHARGE-AF (C index range, 0.720-0.824) and Predict-AF (0.749-0.831) had largely comparable discrimination, both favorable to continuous age (0.675-0.801). Calibration was similar using CHARGE-AF (slope range, 0.67-0.87) and Predict-AF (0.65-0.83). Net reclassification improvement using Predict-AF versus CHARGE-AF was modest (net reclassification improvement range, 0.024-0.057) but more favorable among individuals aged <65 years (0.062-0.11). Using Predict-AF among 99 530 individuals aged ≥65 years across each sample, 70 849 had AF risk <5%, of whom 69 067 (97.5%) did not develop AF, whereas 28 681 had AF risk ≥5%, of whom 2264 (7.9%) developed AF. Of 11 379 individuals aged <65 years with AF risk ≥5%, 435 (3.8%) developed AF before age 65 years, with roughly half (46.9%) meeting anticoagulation criteria. CONCLUSIONS: AF risk estimation using clinical factors may prioritize individuals for AF screening more precisely than the age threshold endorsed in current guidelines. The additional value of genetic predisposition is modest but greatest among younger individuals.
Abbreviated Antiplatelet Therapy in Patients at High Bleeding Risk With or Without Oral Anticoagulant Therapy After Coronary Stenting: An Open-Label, Randomized, Controlled Trial.
Smits PC, Frigoli E, Tijssen J … +26 more , Jüni P, Vranckx P, Ozaki Y, Morice MC, Chevalier B, Onuma Y, Windecker S, Tonino PAL, Roffi M, Lesiak M, Mahfoud F, Bartunek J, Hildick-Smith D, Colombo A, Stankovic G, Iñiguez A, Schultz C, Kornowski R, Ong PJL, Alasnag M, Rodriguez AE, Moschovitis A, Laanmets P, Heg D, Valgimigli M, MASTER DAPT Investigators
Circulation · 2021 Oct · PMID 34455849 · Full text
BACKGROUND: The optimal duration of antiplatelet therapy (APT) in patients at high bleeding risk with or without oral anticoagulation (OAC) after coronary stenting remains unclear. METHODS: In the investigator-initiated,...
BACKGROUND: The optimal duration of antiplatelet therapy (APT) in patients at high bleeding risk with or without oral anticoagulation (OAC) after coronary stenting remains unclear. METHODS: In the investigator-initiated, randomize, open-label MASTER DAPT trial (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Standard DAPT Regimen), 4579 patients at high bleeding risk were randomized after 1-month dual APT to abbreviated or nonabbreviated APT strategies. Randomization was stratified by concomitant OAC indication. In this subgroup analysis, we report outcomes of populations with or without an OAC indication. In the population with an OAC indication, patients changed immediately to single APT for 5 months (abbreviated regimen) or continued ≥2 months of dual APT and single APT thereafter (nonabbreviated regimen). Patients without an OAC indication changed to single APT for 11 months (abbreviated regimen) or continued ≥5 months of dual APT and single APT thereafter (nonabbreviated regimen). Coprimary outcomes at 335 days after randomization were net adverse clinical outcomes (composite of all-cause death, myocardial infarction, stroke, and Bleeding Academic Research Consortium 3 or 5 bleeding events); major adverse cardiac and cerebral events (all-cause death, myocardial infarction, and stroke); and type 2, 3, or 5 Bleeding Academic Research Consortium bleeding. RESULTS: Net adverse clinical outcomes or major adverse cardiac and cerebral events did not differ with abbreviated versus nonabbreviated APT regimens in patients with OAC indication (n=1666; hazard ratio [HR], 0.83 [95% CI, 0.60-1.15]; and HR, 0.88 [95% CI, 0.60-1.30], respectively) or without OAC indication (n=2913; HR, 1.01 [95% CI, 0.77-1.33]; or HR, 1.06 [95% CI, 0.79-1.44]; =0.35 and 0.45, respectively). Bleeding Academic Research Consortium 2, 3, or 5 bleeding did not significantly differ in patients with OAC indication (HR, 0.83 [95% CI, 0.62-1.12]) but was lower with abbreviated APT in patients without OAC indication (HR, 0.55 [95% CI, 0.41-0.74]; =0.057). The difference in bleeding in patients without OAC indication was driven mainly by a reduction in Bleeding Academic Research Consortium 2 bleedings (HR, 0.48 [95% CI, 0.33-0.69]; =0.021). CONCLUSIONS: Rates of net adverse clinical outcomes and major adverse cardiac and cerebral events did not differ with abbreviated APT in patients with high bleeding risk with or without an OAC indication and resulted in lower bleeding rates in patients without an OAC indication. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03023020.
Opioid Use and Its Relationship to Cardiovascular Disease and Brain Health: A Presidential Advisory From the American Heart Association.
Chow SL, Sasson C, Benjamin IJ … +5 more , Califf RM, Compton WM, Oliva EM, Robson C, Sanchez EJ
Circulation · 2021 Sep · PMID 34407637 · Publisher ↗
The misuse of opioids continues to be epidemic, resulting in dependency and a recent upsurge in drug overdoses that have contributed to a significant decrease in life expectancy in the United States. Moreover, recent dat...
The misuse of opioids continues to be epidemic, resulting in dependency and a recent upsurge in drug overdoses that have contributed to a significant decrease in life expectancy in the United States. Moreover, recent data suggest that commonly used opioids for the management of pain may produce undesirable pharmacological actions and interfere with critical medications commonly used in cardiovascular disease and stroke; however, the impact on outcomes remains controversial. The American Heart Association developed an advisory statement for health care professionals and researchers in the setting of cardiovascular and brain health to synthesize the current literature, to provide approaches for identifying patients with opioid use disorder, and to address pain management and overdose. A literature and internet search spanning from January 1, 2012, to February 15, 2021, and limited to epidemiology studies, reviews, consensus statements, and guidelines in human subjects was conducted. Suggestions and considerations listed in this document are based primarily on published evidence from this review whenever possible, as well as expert opinion. Several federal and institutional consensus documents and clinical resources are currently available to both patients and clinicians; however, none have specifically addressed cardiovascular disease and brain health. Although strategic tools and therapeutic approaches for recognition of opioid use disorder and safe opioid use are available for health care professionals who manage patients with cardiovascular disease and stroke, high-quality evidence does not currently exist. Therefore, there is an urgent need for more research to identify the most effective approaches to improve care for these patients.
Coronary Artery Calcium Assessed Years Before Was Positively Associated With Subtle White Matter Injury of the Brain in Asymptomatic Middle-Aged Men: The Framingham Heart Study.
Suzuki H, Davis-Plourde K, Beiser A … +8 more , Kunimura A, Miura K, DeCarli C, Maillard P, Mitchell GF, Vasan RS, Seshadri S, Fujiyoshi A
Circ Cardiovasc Imaging · 2021 Jul · PMID 34256573 · Full text
BACKGROUND: Using magnetic resonance diffusion tensor imaging, we previously showed a cross-sectional association between carotid-femoral pulse wave velocity, a measure of aortic stiffness, and subtle white matter injury...
BACKGROUND: Using magnetic resonance diffusion tensor imaging, we previously showed a cross-sectional association between carotid-femoral pulse wave velocity, a measure of aortic stiffness, and subtle white matter injury in clinically asymptomatic middle-age adults. While coronary artery calcium (CAC) is a robust measure of atherosclerosis, and a predictor of stroke and dementia, whether it predicts diffusion tensor imaging-based subtle white matter injury in the brain remains unknown. METHODS: In FHS (Framingham Heart Study), an observational study, third-generation participants were assessed for CAC (2002-2005) and brain magnetic resonance imaging (2009-2014). Outcomes were diffusion tensor imaging-based measures; free water, fractional anisotropy, and peak width of mean diffusivity. After excluding the participants with neurological conditions and missing covariates, we categorized participants into 3 groups according to CAC score (0, 0 < to 100, and >100) and calculated a linear trend across the CAC groups. In secondary analyses treating CAC score as continuous, we computed slope of the outcomes per 20 to 80th percentiles higher log-transformed CAC score using linear regression. RESULTS: In a total of 1052 individuals analyzed (mean age 45.4 years, 45.4% women), 71.6%, 22.4%, and 6.0% had CAC score of 0, 0 < to 100, and >100, respectively. We observed a significant linear trend of fractional anisotropy, but not other measures, across the CAC groups after multivariable adjustment. In the secondary analyses, CAC was associated with lower fractional anisotropy in men but not in women. CONCLUSIONS: CAC may be a promising tool to predict prevalent subtle white matter injury of the brain in asymptomatic middle-aged men.
Deep Learning to Predict Cardiac Magnetic Resonance-Derived Left Ventricular Mass and Hypertrophy From 12-Lead ECGs.
Khurshid S, Friedman S, Pirruccello JP … +8 more , Di Achille P, Diamant N, Anderson CD, Ellinor PT, Batra P, Ho JE, Philippakis AA, Lubitz SA
Circ Cardiovasc Imaging · 2021 Jun · PMID 34126762 · Full text
BACKGROUND: Classical methods for detecting left ventricular (LV) hypertrophy (LVH) using 12-lead ECGs are insensitive. Deep learning models using ECG to infer cardiac magnetic resonance (CMR)-derived LV mass may improve...
BACKGROUND: Classical methods for detecting left ventricular (LV) hypertrophy (LVH) using 12-lead ECGs are insensitive. Deep learning models using ECG to infer cardiac magnetic resonance (CMR)-derived LV mass may improve LVH detection. METHODS: Within 32 239 individuals of the UK Biobank prospective cohort who underwent CMR and 12-lead ECG, we trained a convolutional neural network to predict CMR-derived LV mass using 12-lead ECGs (left ventricular mass-artificial intelligence [LVM-AI]). In independent test sets (UK Biobank [n=4903] and Mass General Brigham [MGB, n=1371]), we assessed correlation between LVM-AI predicted and CMR-derived LV mass and compared LVH discrimination using LVM-AI versus traditional ECG-based rules (ie, Sokolow-Lyon, Cornell, lead aVL rule, or any ECG rule). In the UK Biobank and an ambulatory MGB cohort (MGB outcomes, n=28 612), we assessed associations between LVM-AI predicted LVH and incident cardiovascular outcomes using age- and sex-adjusted Cox regression. RESULTS: LVM-AI predicted LV mass correlated with CMR-derived LV mass in both test sets, although correlation was greater in the UK Biobank (r=0.79) versus MGB (r=0.60, P<0.001 for both). When compared with any ECG rule, LVM-AI demonstrated similar LVH discrimination in the UK Biobank (LVM-AI c-statistic 0.653 [95% CI, 0.608 -0.698] versus any ECG rule c-statistic 0.618 [95% CI, 0.574 -0.663], P=0.11) and superior discrimination in MGB (0.621; 95% CI, 0.592 -0.649 versus 0.588; 95% CI, 0.564 -0.611, P=0.02). LVM-AI-predicted LVH was associated with incident atrial fibrillation, myocardial infarction, heart failure, and ventricular arrhythmias. CONCLUSIONS: Deep learning-inferred LV mass estimates from 12-lead ECGs correlate with CMR-derived LV mass, associate with incident cardiovascular disease, and may improve LVH discrimination compared to traditional ECG rules.
Randomized Placebo-Controlled Trial of Ferric Carboxymaltose in Heart Failure With Iron Deficiency: Rationale and Design.
Mentz RJ, Ambrosy AP, Ezekowitz JA … +14 more , Lewis GD, Butler J, Wong YW, De Pasquale CG, Troughton RW, O'Meara E, Rockhold FW, Garg J, Samsky MD, Leloudis D, Dugan M, Mundy LM, Hernandez AF, HEART-FID Trial Investigators
Circ Heart Fail · 2021 May · PMID 34003690 · Full text
BACKGROUND: Iron deficiency (ID) has a prevalence of ≈40% to 50% among patients in heart failure (HF) with reduced ejection fraction and is associated with worse prognosis. Several trials demonstrated that intravenous fe...
BACKGROUND: Iron deficiency (ID) has a prevalence of ≈40% to 50% among patients in heart failure (HF) with reduced ejection fraction and is associated with worse prognosis. Several trials demonstrated that intravenous ferric carboxymaltose leads to early and sustained improvement in patient-reported outcomes and functional capacity in patients with HF with reduced ejection fraction with ID, yet morbidity and mortality data are limited. METHODS: The objective of the HEART-FID trial (Ferric Carboxymaltose in Heart Failure With Iron Deficiency) is to assess efficacy and safety of ferric carboxymaltose compared with placebo as treatment for symptomatic HF with reduced ejection fraction with ID. HEART-FID is a multicenter, randomized, double-blind, placebo-controlled trial enrolling ≈3014 patients at ≈300 international centers. Eligible patients are aged ≥18 years in stable chronic HF with New York Heart Association functional class II to IV symptoms, ejection fraction ≤40%, ID (ferritin <100 ng/mL or ferritin 100-300 ng/mL with a transferrin saturation <20%), and documented HF hospitalization or elevated N-terminal pro-brain natriuretic peptide. Consented patients are assigned to ferric carboxymaltose or placebo at baseline, with repeated visits/assessments every 6 months for additional study drug based on hemoglobin and iron indices for the trial duration. The primary end point is a hierarchical composite of death and HF hospitalization at 12 months and change from baseline to 6 months in the 6-minute walk test distance. CONCLUSIONS: The HEART-FID trial will inform clinical practice by clarifying the role of long-term treatment with intravenous ferric carboxymaltose, added to usual care, in ambulatory patients with symptomatic HF with reduced ejection fraction with ID. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037931.
Plasma Proteomic Profile Predicts Survival in Heart Failure With Reduced Ejection Fraction.
Gui H, She R, Luzum J … +6 more , Li J, Bryson TD, Pinto Y, Sabbah HN, Williams LK, Lanfear DE
Circ Genom Precis Med · 2021 Jun · PMID 33999650 · Full text
BACKGROUND: It remains unclear whether the plasma proteome adds value to established predictors in heart failure (HF) with reduced ejection fraction (HFrEF). We sought to derive and validate a plasma proteomic risk score...
BACKGROUND: It remains unclear whether the plasma proteome adds value to established predictors in heart failure (HF) with reduced ejection fraction (HFrEF). We sought to derive and validate a plasma proteomic risk score (PRS) for survival in patients with HFrEF (HFrEF-PRS). METHODS: Patients meeting Framingham criteria for HF with EF<50% were enrolled (N=1017) and plasma underwent SOMAscan profiling (4453 targets). Patients were randomly divided 2:1 into derivation and validation cohorts. The HFrEF-PRS was derived using Cox regression of all-cause mortality adjusted for clinical score and NT-proBNP (N-terminal pro-B-type natriuretic peptide), then was tested in the validation cohort. Risk stratification improvement was evaluated by C statistic, integrated discrimination index, continuous net reclassification index, and median improvement in risk score for 1-year and 3-year mortality. RESULTS: Participants' mean age was 68 years, 48% identified as Black, 35% were female, and 296 deaths occurred. In derivation (n=681), 128 proteins associated with mortality, 8 comprising the optimized HFrEF-PRS. In validation (n=336) the HFrEF-PRS associated with mortality (hazard ratio, 2.27 [95% CI, 1.84-2.82], =6.3×10), Kaplan-Meier curves differed significantly between HFrEF-PRS quartiles (=2.2×10), and it remained significant after adjustment for clinical score and NT-proBNP (hazard ratio, 1.37 [95% CI, 1.05-1.79], =0.021). The HFrEF-PRS improved metrics of risk stratification (C statistic change, 0.009, =0.612; integrated discrimination index, 0.041, =0.010; net reclassification index=0.391, =0.078; median improvement in risk score=0.039, =0.016) and associated with cardiovascular death and HF phenotypes (eg, 6-minute walk distance, EF change). Most HFrEF-PRS proteins had little known connection to HFrEF. CONCLUSIONS: A plasma multiprotein score improved risk stratification in patients with HFrEF and identified novel candidates.
Biomarker-Based Risk Prediction With the ABC-AF Scores in Patients With Atrial Fibrillation Not Receiving Oral Anticoagulation.
Benz AP, Hijazi Z, Lindbäck J … +5 more , Connolly SJ, Eikelboom JW, Oldgren J, Siegbahn A, Wallentin L
Circulation · 2021 May · PMID 33849281 · Publisher ↗
BACKGROUND: The novel ABC (Age, Biomarkers, Clinical History) scores outperform traditional risk scores for stroke, major bleeding, and death in patients with atrial fibrillation (AF) receiving oral anticoagulation. To r...
BACKGROUND: The novel ABC (Age, Biomarkers, Clinical History) scores outperform traditional risk scores for stroke, major bleeding, and death in patients with atrial fibrillation (AF) receiving oral anticoagulation. To refine their utility, the ABC-AF scores needed to be validated in patients not receiving oral anticoagulation. METHODS: We measured plasma levels of the ABC biomarkers (N-terminal pro-B-type natriuretic peptide, cardiac troponin-T, and growth-differentiation factor 15) to apply the previously developed ABC-AF scores in patients with AF receiving aspirin (n=3195) or aspirin and clopidogrel (n=1110) in 2 large clinical trials. Calibration was assessed by comparing estimated with observed 1-year risks. Cox regression models were used for recalibration. Discrimination was evaluated separately for the aspirin-only and the overall cohort (n=4305). RESULTS: The ABC-AF-stroke score yielded a c-index of 0.70 (95% CI, 0.67-0.73) in both cohorts. The ABC-AF-bleeding score had a c-index of 0.76 (95% CI, 0.71-0.81) in the aspirin-only cohort and 0.73 (95% CI, 0.69-0.77) overall. Both scores were superior to risk scores recommended by current guidelines. The ABC-AF-death score yielded a c-index of 0.78 (95% CI, 0.76-0.80) overall. Calibrated in patients receiving oral anticoagulation, the ABC-AF-stroke score underestimated and the ABC-AF-bleeding score overestimated the risk of events in both cohorts. These scores were recalibrated for prediction of absolute event rates in the absence of oral anticoagulation. CONCLUSIONS: The biomarker-based ABC-AF scores showed better discrimination than traditional risk scores and were recalibrated for precise risk estimation in patients not receiving oral anticoagulation. They can now provide improved decision support on treatment of an individual patient with AF.
Remnant Cholesterol and Common Carotid Artery Intima-Media Thickness in Patients With Ischemic Stroke.
Qian S, You S, Sun Y … +8 more , Wu Q, Wang X, Tang W, Dong X, Liu CF, Xu T, Cao Y, Zhong C
Circ Cardiovasc Imaging · 2021 Apr · PMID 33832329 · Publisher ↗
BACKGROUND: Remnant cholesterol makes great contribution to residual risk of cardiovascular disease, but population-based evidence on the relationship between remnant cholesterol and atherosclerosis is rare. Common carot...
BACKGROUND: Remnant cholesterol makes great contribution to residual risk of cardiovascular disease, but population-based evidence on the relationship between remnant cholesterol and atherosclerosis is rare. Common carotid artery intima-media thickness (cIMT) is an imaging marker of subclinical atherosclerosis. We aimed to explore the association between remnant cholesterol levels and cIMT in patients with ischemic stroke. METHODS: One thousand four hundred ninety-six ischemic stroke patients with baseline serum lipids and carotid artery imaging data were included in this analysis. Fasting remnant cholesterol was calculated as total cholesterol minus HDL (high-density lipoprotein) cholesterol minus LDL (low-density lipoprotein) cholesterol. Abnormal cIMT was defined as mean cIMT and maximum cIMT value ≥1 mm. Logistic regression and restricted cubic spline models were used to assess the relationships between remnant cholesterol levels and abnormal cIMT. RESULTS: The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of remnant cholesterol were 2.06 (1.46-2.91) for abnormal mean cIMT and 1.70 (1.23-2.35) for abnormal maximum cIMT. There were linear associations between remnant cholesterol levels and both abnormal mean cIMT ( for linearity, <0.001) and abnormal maximum cIMT ( for linearity, 0.003). Moreover, the remnant cholesterol-cIMT association remained significant in the subsample of patients with optimal LDL cholesterol levels (n=179). CONCLUSIONS: Elevated fasting remnant cholesterol levels were positively associated with mean cIMT and maximum cIMT in patients with ischemic stroke, even in patients with optimal LDL cholesterol levels. Future prospective studies are needed to verify our findings and to assess the effect of remnant cholesterol-lowering interventions in patients with ischemic stroke.
Prognostic Role of Prior Heart Failure Hospitalization Among Patients Hospitalized for Worsening Chronic Heart Failure.
Blumer V, Mentz RJ, Sun JL … +6 more , Butler J, Metra M, Voors AA, Hernandez AF, O'Connor CM, Greene SJ
Circ Heart Fail · 2021 Apr · PMID 33775110 · Full text
BACKGROUND: Hospitalization for heart failure (HF) is associated with increased risk of death among patients with chronic HF. The degree to which hospitalization for HF is a distinct biologic entity with independent prog...
BACKGROUND: Hospitalization for heart failure (HF) is associated with increased risk of death among patients with chronic HF. The degree to which hospitalization for HF is a distinct biologic entity with independent prognostic value versus a marker of higher risk chronic HF patients is unclear. METHODS: After excluding patients with new-onset HF, the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) included 4205 patients hospitalized for worsening chronic HF with reduced or preserved ejection fraction. The present analysis compared patients by presence or absence of prior HF hospitalization within 12 months and by timing of prior HF hospitalization relative to index hospitalization. Associations with 180-day all-cause mortality were assessed, including adjustment for 27 prespecified clinical factors. RESULTS: Overall, 2241 (53.3%) patients had a HF hospitalization within the prior 12 months and 1964 (46.7%) did not. Mortality rates at 180 days were 15.5% and 11.9%, respectively. In unadjusted analyses, prior HF hospitalization was associated with increased risk of 180-day mortality (HR, 1.35 [95% CI, 1.14-1.59]; <0.01). After adjustment, the point estimate was attenuated and the association not statistically significant (HR, 1.18 [95% CI, 0.99-1.40]; =0.064). Similarly, after adjustment, compared with patients without prior hospitalization, prior HF hospitalization was not associated with mortality, irrespective of timing (0-4 months: HR, 1.10 [95% CI, 0.87-1.39], =0.41; 4-8 months: HR, 0.95 [95% CI, 0.70-1.27]; =0.72; 8-12 months: HR, 1.06 [95% CI, 0.74-1.51], =0.77; >12 months: HR, 0.81 [95% CI, 0.63-1.06], =0.12). CONCLUSIONS: In this cohort of patients hospitalized for worsening HF, prior HF hospitalization was not associated with 180-day mortality after comprehensively accounting for patient characteristics measured during the index patient visit. Clinical confounders measured at the point-of-care may explain previously observed associations between prior HF hospitalization and mortality, and these clinical factors may be a more direct means of predicting patient survival. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00475852.
Utilization and Availability of Advanced Imaging in Patients With Acute Ischemic Stroke.
Kim Y, Lee S, Abdelkhaleq R … +11 more , Lopez-Rivera V, Navi B, Kamel H, Savitz SI, Czap AL, Grotta JC, McCullough LD, Krause TM, Giancardo L, Vahidy FS, Sheth SA
Circ Cardiovasc Qual Outcomes · 2021 Apr · PMID 33757311 · Publisher ↗
BACKGROUND: Recent clinical trials have established the efficacy of endovascular stroke therapy and intravenous thrombolysis using advanced imaging, particularly computed tomography perfusion (CTP). The availability and...
BACKGROUND: Recent clinical trials have established the efficacy of endovascular stroke therapy and intravenous thrombolysis using advanced imaging, particularly computed tomography perfusion (CTP). The availability and utilization of CTP for patients and hospitals that treat acute ischemic stroke (AIS), however, is uncertain. METHODS: We performed a retrospective cross-sectional analysis using 2 complementary Medicare datasets, full sample Texas and 5% national fee-for-service data from 2014 to 2017. AIS cases were identified using , and , coding criteria. Imaging utilization performed in the initial evaluation of patients with AIS was derived using Current Procedural Terminology codes from professional claims. Primary outcomes were utilization of imaging in AIS cases and the change in utilization over time. Hospitals were defined as imaging modality-performing if they submitted at least 1 claim for that modality per calendar year. The National Medicare dataset was used to validate state-level findings, and a local hospital-level cohort was used to validate the claims-based approach. RESULTS: Among 50 797 AIS cases in the Texas Medicare fee-for-service cohort, 64% were evaluated with noncontrast head CT, 17% with CT angiography, 3% with CTP, and 33% with magnetic resonance imaging. CTP utilization was greater in patients treated with endovascular stroke therapy (17%) and intravenous thrombolysis (9%). CT angiography (4%/y) and CTP (1%/y) utilization increased over the study period. These findings were validated in the National dataset. Among hospitals in the Texas cohort, 100% were noncontrast head CT-performing, 77% CT angiography-performing, and 14% CTP-performing in 2017. Most AIS cases (69%) were evaluated at non-CTP-performing hospitals. CTP-performing hospitals were clustered in urban areas, whereas large regions of the state lacked immediate access. CONCLUSIONS: In state-wide and national Medicare fee-for-service cohorts, CTP utilization in patients with AIS was low, and most patients were evaluated at non-CTP-performing hospitals. These findings support the need for alternative means of screening for AIS recanalization therapies.
Renal Sympathetic Denervation in Patients With Heart Failure With Preserved Ejection Fraction.
Kresoja KP, Rommel KP, Fengler K … +8 more , von Roeder M, Besler C, Lücke C, Gutberlet M, Desch S, Thiele H, Böhm M, Lurz P
Circ Heart Fail · 2021 Mar · PMID 33706547 · Publisher ↗
BACKGROUND: Arterial hypertension is the most common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and mediates adverse hemodynamics through related aortic stiffness and increased pu...
BACKGROUND: Arterial hypertension is the most common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and mediates adverse hemodynamics through related aortic stiffness and increased pulsatile load. We aimed to investigate the clinical and hemodynamic implications of renal sympathetic denervation (RDN) in patients with HFpEF and uncontrolled arterial hypertension. METHODS: Patients undergoing RDN between 2011 and 2018 in a single-center were retrospectively analyzed and classified as HFpEF (n=99) or no HF (n=65). Stroke volume index and aortic distensibility were measured through cardiac magnetic resonance imaging, and left ventricular (LV) systolic and diastolic properties were assessed echocardiographically. RESULTS: At baseline, patients with HFpEF had higher stroke volume index (median 40 [interquartile range, 33-48] versus 33 [26-40] mL/m, =0.002), pulse pressure (69 [63-77] versus 61 [55-67] mm Hg, <0.001), but lower LV-VPES (18 [10-28] versus 24 [15-40] mL, =0.007) and aortic distensibility (1.5 [1.1-2.6] versus 2.7 [1.1-3.5] 10 mm Hg, =0.013) as compared to no-HF patients. Systolic blood pressure decreased comparable in patients with HFpEF and no-HF patients following RDN (-9 [-16 to -2], <0.001). After RDN stroke volume index (-3 [-9 to +3] mL/m, =0.011) decreased and aortic distensibility (0.2 [-0.1 to +1.1] 10 mm Hg, =0.007) and systolic stiffness (<0.001) increased in HFpEF patients. LV diastolic stiffness and LV filling pressures as well as NT-proBNP (N-terminal pro-B-type natriuretic peptide) decreased after RDN in patients with HFpEF (=0.032, =0.043, and <0.001, respectively). CONCLUSIONS: Patients with HFpEF undergoing RDN showed increased stroke volume index, vascular, and LV stiffness as compared to no-HF patients. Following RDN those hemodynamic alterations and reduced systolic and diastolic LV stiffness were partly normalized, implying RDN might be a potential therapeutic strategy for arterial hypertension and HFpEF.
A Case of Rapidly Progressing Granulomatous Myocarditis: What Is the Diagnosis?
Cao J, Schwartz YY, Lomasney JW … +6 more , Narang A, Okwuosa IS, Avery R, Passman RS, Cooper LT, Vorovich E
Circ Heart Fail · 2021 Mar · PMID 33677978 · Publisher ↗
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